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					             Associations between health behaviours, metabolic
   Title     control, serum TNF-ALPHA and periodontal status in
             Chinese type-2 diabetics


Author(s)    Movva, Leela R



 Citation



Issue Date   2004



  URL        http://hdl.handle.net/10722/40703



  Rights     unrestricted
ASSOCIATIONS BETWEEN HEALTH BEHAVIOURS,
METABOLIC CONTROL, SERUM TNF-ALPHA AND
  PERIODONTAL STATUS IN CHINESE TYPE-2
                    DIABETICS

             This dissertation is submitted to
              The University of Hong Kong
         in partial fulfillment of the requirements
                     for the degree of



               Master of Dental Surgery
                    (Periodontology)
                            By
                     Leela. R. Mowa
                           2004




                      Periodontology
                   Faculty of Dentistry
              The University of Hong Kong
                        Hong Kong
Associations between health behaviours, metabolic
control, serum TNF-alpha and periodontal status in
             Chinese type-2 diabetics




                   Leela. R. Mowa
                       2004
                                  Contents
Acknowledgments                                             iii
Abstract                    .                               iv

Part I Literature review                                     1
1.1 Introduction                                             2
1.2 Scientific knowledge on diabetes mellitus                3
  1.2.1 History                                              3
  1.2.2 Definition...                                        4
  1.2.3 Classification of diabetes mellitus                  5
  1.2.4 Epidemiology                                         6
  1.2.5 Etio-pathogenesis                                    7
  1.2.6 Clinical presentations and complications             9
  1.2.7 Diagnosis                                            9
  1.2.8 Management                                          10
1.3. Diabetes and Oral diseases                  .          12
  1.3.1 Xerostomia and Parotid swelling                     12
  1.3.2Candidiasis                                          13
  1.3.3 Lichen Planus & Leukoplakia                         14
  1.3.4 Dental Caries                                       14
  1.3.5 Delayed wound healing                               15
  1.3.6 Periodontal diseases                                15
1.4. Periodontal diseases and associated risk factors       20
  1.4.1 General health behaviour                            20
          1.4.1.1 Systemic factors                          21
          1.4.1.2 Dietary & obesity factors                 24
          1.4.1.3 Psychological factors                     29
  1.4.2 Oral health behaviour                               30
  1.4.3 Inflammatory factors                                31
  1.4.4 Conclusion                                          32

Part II Clinical study                                      33
2.1. Scientific rationale of the study                  .   34
  2.1.1 Aims                                                34
  2.1.2 Objectives                                          34
  2.1.3 Hypothesis                                          35
2.2. Materials and methods                                  37
  2.2.1 Study Design                                        37
  2.2.2 Inclusion and exclusion criteria                    37
  2.2.3 Assessment of clinical parameters                   38
          2.2.3.1 Oral health parameters                    38
          2.2.3.2 Metabolic and general health              39
2.3. Results                                                41
  2.3.1 Demographic characteristics                         41
  2.3.2 Distribution of the data                            41
  2.3.3 Hypothesis testing                                  47
          2.3.3.1 General health behaviour                  47
          2.3.3.2 Diet behaviour                            49
                                                                             Contents



         2.3.3.3 Perceived fatigue                                                51
         2.3.3.4 Oral health behaviour                                            52
         2.3.3.5 Obesity                                                          54
         2.3.3.6 Psychological behaviour (Distress)                               54
         2.3.3.7 Oral hygiene status                                              55
         2.3.3.8 Metabolic control                                                58
         2.3.3.9 Serum TNF-alpha levels                                           61
         2.3.3.10 Missing teeth                                                   62

Part III Discussions and conclusions                                              66
3.1. Discussion of population and methods                                         67
  3.1.1 Study population                                                           67
  3.1.2 Self reporting and clinical examination                                    67
3.2, Discussion of the results                                                    68
  3.2.1 Health behaviours                                                         68
          3.2.1.1 General health behaviour                                        68
          3.2.1.2 Diet behaviour                                                  69
          3.2.1.3 Perceived fatigue                                               70
          3.2.1.4 Oral health behaviour                                           71
  3.2.2 Obesity                                                                    72
  3.2.3 Metabolic control                                                          72
          3.2.3.1 Serum TNF-alpha                                                 72
          3.2.3.2 Diabetic status                                                 73
          3.2.3.3 Duration of diabetes                                            74
  3.2.4 Periodontal status                                                         74
          3.2.4.1 Probing pocket depth & Probing attachment level                 75
          3.2.4.2 Gingival status                                                 76
  3.2.5 Missing teeth                                                              76
  3.2.6 Associations between the variables and their relative significance         78
  3.2.7 Conclusions and clinical implications                                      82

Appendix                                                                          84
Appendix - I                                                                      85
Appendix - II                                                                     90
Appendix - III                                                                    95

References....                                                                    96




                                           11
Ill
                                                                                   Abstract



Abstract:

Objectives: To assess the associations between health behaviours, metabolic control, serum

TNF-alpha and periodontal status in Chinese type 2 diabetics.

Methods: 208, nonsmoking type 2 diabetic patients aged 40-70 years (51% female)

attending an outpatient diabetic clinic were examined. All patients filled in structured

questionnaires and were clinically examined. Glycated hemoglobin (HbAlc) and serum

TNF-alpha were measured using commercial kits from blood drawn on the day of

examination

Results: General health behaviour was significantly associated with diet behaviour

(r=0.174) and distress (r = 0.197). Diet behaviour of females was better than males

(/K0.001). Perceived fatigue was negatively associated with oral health behaviour (r=-

0.160). Distress was lower in the younger age group 40-50 compared to 51-70 (/K0.01).

Mean serum TNF-alpha level was 0.65pg/ml and this was not associated with any variable.

The prevalence of severe periodontal disease was 70.6%. Oral hygiene status was

significantly associated with mean PPD (r=0.36) and mean PAL (r=0.327). HbAlc levels

were significantly associated with mean PPD (r=0.202) and mean PAL (r=0.180). Subjects

with a longer history of diabetes (>5 years) had significantly deeper mean PPD (p<0.04),

higher mean PAL (p<0.01) and more missing anterior teeth (p<0.025).

Conclusion: In this group of type-2 diabetics the severity of periodontal disease was found

to be associated with oral hygiene, metabolic control and duration of diabetes. Serum TNF-

alpha and health behaviours did not seem to be associated with periodontal disease status.




                                            IV
               Literature Review




      Parti
Literature review
                                                                           Literature Review



Part I. Literature Review

LI Introduction

Arguably, periodontitis is most cumbersome to define in any population as we can see

different combinations of definition repeatedly in the literature (Page & Schroeder, 1982;

Scherp, 1964; The American Academy of Periodontology, 2001). The complex and multi-

factorial nature of periodontal disease may be a possible reason for failure to generalize the

presentation of periodontal disease. However, various combinations of definitions in the

literature are maybe also due to variations in observer choice in selecting the parameters to

define along with variation in the nature of the presenting condition.

The current concept concerning the etiology of periodontitis considers three factors which

determine whether active periodontitis will occur or not in a subject: a susceptible host, the

presence of pathogenic bacterial species, and the absence of so called beneficial bacteria

(Slots & Rams, 1991; Socransky & Haffajee, 1992). Moreover, the diseased condition may

be aggravated by certain risk factors such as smoking, ageing, uncontrolled diabetes,

genetic factors, geographic location, race, compliance, bacterial specificity, host response

factors, socioeconomic factors, psychological factors and local factors. In thorough

understanding and comprehensive management of periodontitis, careful assessment of these

factors along with disease condition offers rich dividends.

It is indeed high time to have a clinical study combining as many risk factors as possible to

assess the periodontal condition. We have made an attempt to study a type-2 diabetic patient

population combining behavioural factors, inflammatory factors, and psychological factors

with diabetic control and periodontal status. Genetic factors were not considered as the

Chinese population seems to have low prevalence of interleukin-1 polymorphism (Armitage
                                                                            Literature Review



et al, 2000). Bacterial factors, immunological factors and treatment responses are studied

by other members of the current research group.

1.2. Scientific knowledge on diabetes mellitus

1.2.1. History:

The term diabetes is derived from the Greek word meaning siphon, or the passing through

of water, while mellitus is Latin for honeysweet. The earliest civilizations (Asia Minor,

China, Egypt, and India) described diabetes as boils and infections, excessive thirst, loss

of weight, and the passing of large quantities of a honeysweet urine which often drew ants

and flies. These earliest descriptions, for example Papyrus Ebers, an Egyptian document

dated from about 1550 B.C. by physician Hesy-Ra mentions polyurea as a symptom. In

the 1st century A.D, Arateus described diabetes as £the melting down of flesh and limbs

into urine'.

The earliest management of diabetes followed by Hesy-Ra was that those afflicted with

the malady go on a diet of bear, fruits, grains, and honey, which was reputed to stifle the

excessive urination. Indian writings from the same era attributed the disease to

overindulgence in food and drink. Accounts of the diets of the middle class in northern

European countries during the 15th, 16th and 17th centuries described meals consisting of

many courses of roast meats dripping with fat, rich and sugary pastries, and plenty of

butter and cream, but little green leafy vegetables. It is therefore not surprising that many

cases of diabetes were reported during these times of abundance. It is noteworthy too that

during this period doctors had to taste the urine of patients for sweetness in order to detect

the disease. Soon, there emerged two schools of thought concerning diets. One school

believed in dietary replacement of the sugar lost in the urine, while the other believed in

restriction of carbohydrate so as to reduce the effects which were attributed to an excess

of sugar. The first school was exemplified by the British physician Willis, who in 1675,
                                                                            Literature Review



recommended a diet limited to milk, barley water, and bread. This diet was high in

carbohydrate, but low in calories. In 1797, started a long-lasting trend towards high-fat,

high-protein, and low carbohydrate diets by prescribing mainly meat and fat. None of the

physicians of those times knew much about the nature of the abnormality since various

writers referred to it as a disease of the blood, kidneys, liver, or stomach. Nevertheless,

some of the patients appeared to have been helped by the diets which were prescribed as

evidenced by reductions in the amounts of sugar spilled in the urine. The restriction of the

caloric intake appears to have been the most effective therapy since the French physician

Bouchardat observed that the limited availability of food in Paris during the Franco-

Prussian war of 1870 to 1871 resulted in marked reduction in the sugar spilled by his

diabetic patients.

The management of diabetes has been taken to heights with the discovery of insulin in early

1920. Sir Frederick Banting and Charles Best discovered insulin at the University of

Toronto in 1921-22. But the discovery of insulin was a collaborative process of a four-man

research team, physician Frederick Banting, graduate student Charles Best, Professor of

Physiology Macleod, and biochemist Collip. In recognition of their achievement, the 1923

Nobel Prize in Physiology and Medicine was awarded to Frederick Banting and Macleod,

who in turn shared their prize with Charles Best and Collip respectively.

1.2.2. Definition:

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting

from defects in insulin secretion, insulin action or both (American Diabetic Association,

2004; Guillausseau, 1997; Lebovitz, 2001; Rayburn, 1997; Sacks, 1997).
                                                                          Literature Review



1.2.3. Classification of diabetes mellitus:

Tablel.Etiologic classification of diabetes mellittis

I. Type-1 diabetes* (B-cell destruction, usually leading to absolute insulin
   deficiency)
   A. Immune mediated
   B. Idiopathic
n. Type-2 diabetes* (may range from predominantly insulin resistance with relative
   insulin deficiency to a predominantly secretary defect with insulin resistance)
HI. Other specific types
    A. Genetic defects of B-cell function
       1. Chromosome 12, HNF-la (MODY3)
       2. Chromosome 7, glucokinase (MODY2)
       3. Chromosome 20, HNF-4 a (MODY1)
       4. Mitochondrial DNA
       5. Others
    B. Genetic defects in insulin action
       1. Type A insulin resistance
       2. Leprechaunism
       3. Rabson-Mendenhall syndrome
       4. Lipoatrophic diabetes
       5. Others
    C. Diseases of the exocrine pancreas
       1. Pancreatitis
       2. Trauma/pancreatectomy
       3. Neoplasia
       4. Cystic fibrosis
       5. Hemochromatosis
       6. Fibrocalculous pancreatopathy
       7. Others
    D. Endocrinopathies
       1. Acromegaly
       2. Gushing's syndrome
       3. Glucagonoma
       4. Pheochromocytoma
       5. Hyperthyroidism
       6. Somatostatinoma
       7. Aldosteronoma
       8. Others
    E. Drug- or chemical-induced
       1. Vacor
       2. Pentamidine
       3. Nicotinic acid
       4. Glucocorticoids
       5. Thyroid hormone
       6. Diazoxide
                                                                            Literature Review



       7. 13-adrenergic agonists
       8. Thiazides
       9. Dilantin
       10. a -Interferon
       11. Others
    F. Infections
       1. Congenital rubella
       2. Cytomegalovirus
       3. Others
    G. Uncommon forms of immune-mediated diabetes
       1. "Stiff-man" syndrome
       2. Anti-insulin receptor antibodies
       3. Others
    H. Other genetic syndromes sometimes associated with diabetes
       1. Down's syndrome
       2. Klinefelter's syndrome
       3. Turner's syndrome
       4. Wolfram's syndrome
       5. Friedreich' s ataxia
       6. Huntingdon's chorea
       7. Laurence-Moon-Biedl syndrome
       8. Myotonic dystrophy
       9. Porphyria
       10. Prader-Willi syndrome
       11. Others
IV. Gestational diabetes mellitus (GDM)


Patients -with any form of diabetes may require insulin treatment at some stage of their

disease. Such use of insulin, does not, of it self, classify the patient.

1.2.4. Epidemiology & Prevalence:

In the Chinese population, the prevalence of diabetes rises from < 1% in some rural areas in

mainland China to 6-12% among Chinese living in Hong Kong, Singapore, and Taiwan

(Chou et al., 1992; Pan et al., 1997b; Thai et al., 1987). In Hong Kong, four large-scale

epidemiological studies have been performed since 1987. In 1987 and 1996 the prevalence

of diabetes is reported to be 10% in subjects of age < 65 years (Cockram et al., 1993). This

prevalence increased to 17% in those >75 years of age (Woo et al, 1989). However the

prevalence of diabetes in Hong Kong varied according to the criteria used (Janus et al.,
                                                                            Literature Review



2000). The prevalence rates according to American Diabetic Association (ADA) 1997

criteria is 6.2% with the range from 5.3-7.1%, whereas WHO criteria raises the prevalence

rates up to 9.8% with the range from 8 7-10.9%. It seems like ADA 1997 criteria under

estimates the prevalence rates of diabetes and subsequently the associated risks in this of

population. Further more the rate of progression from impaired glucose tolerance to

diabetes in subjects with at least one risk factor has been reported to be 11% per year with 2

hour plasma glucose as a major predicting factor (Ko et al., 1999). Reported risk factors for

diabetes in Chinese include positive family history of diabetes, obesity, high blood pressure,

dyslipidemia, a past history of gestational diabetes, and a low social class or a high personal

income with low level of education (Ko et al., 2000; Pan et al., 1997a). There are also

synergistic effects between these risk factors with the odds ratios of having diabetes

increasing from 3.7 in subjects with one risk factor to 28.4 in those with four to five risk

factors (Ko et al., 2000).

1.2.5. Etio-pathogenesis:

Several pathogenic processes are involved in the development of diabetes. These range

from autoimmune destruction of the (3-cells of the pancreas with consequent insulin

deficiency (Gerich, 2003) to abnormalities that result in resistance to insulin action

(Hotamisligil et al., 1994). The causes of insulin resistance can be broadly divided into

inherited and acquired causes. Several gene mutations have been described including those

involving the insulin receptor, the insulin receptor subtrate-1, and glycogen synthase genes.

However most genetic defects associated with insulin resistance and type-2 diabetes remain

to be identified. More is known about acquired or life-style related causes of insulin

resistance. The conditions associated with insulin resistance and most commonly associated

with development of type-2 diabetes are aging, obesity, physical inactivity, and pregnancy.

The basis of the abnormalities in carbohydrate, fat, and protein metabolism in diabetes is
                                                                            Literature Review



deficient action of insulin on target tissues. Deficient insulin action results from inadequate

insulin secretion and or diminished tissue response to insulin at one or more points in the

complex pathways of hormone action. Impairment of insulin secretion and defects in insulin

action frequently coexist in the same patient (Gerich, 2003; U.K. Prospective Diabetes

Study Group, 1995), and it is often unclear which abnormality, if either alone, is the

primary cause of the hyperglycemia.

The vast majority of cases of diabetes fall into two broad etiopathogenic categories. In the

first category, type-1 diabetes, the cause is an absolute deficiency of insulin secretion.

Individuals at increased risk of developing this type of diabetes can often be identified by

serological evidence of an autoimmune pathogenic process occurring in the pancreatic islets

and by genetic markers (Pearson et al., 2003). In the other, much more prevalent category,

Type-2 diabetes, the cause is a combination of resistance to insulin action and an inadequate

compensatory insulin secretary response (Gerich, 2003). In the latter category, a degree of

hyperglycemia sufficient to cause pathogenic and functional changes in various target

tissues, but without clinical symptoms, may be present for a long period of time before

diabetes is detected. During this asymptomatic period, it is possible to demonstrate an

abnormality in carbohydrate metabolism by measurement of plasma glucose in the fasting

state or after a challenge with an oral glucose load.

The degree of hyperglycemia may change over time, depending on the extent of the

underlying disease process. A disease process may be present but may not have progressed

far enough to cause hyperglycemia. The same disease process can cause impaired fasting

glucose (IFG) and impaired glucose tolerance (IGT) without fulfilling the criteria for the

diagnosis of diabetes (Harris et al., 1992).
                                                                             Literature Review



1.2.6. Clinical presentations and complications:

Clinical symptoms of marked hyperglycemia include polyuria, polydipsia, weight loss,

some times with polyphagia, and blurred vision. Impairment of growth and susceptibility to

certain infections may also accompany chronic hyperglycemia (Guillausseau, 1997). Acute

life threatening consequences of uncontrolled diabetes are hyperglycemia with ketoacidosis

or the nonketotic hyperosmolar syndrome (Guillausseau, 1997; Rayburn, 1997).

Long term complications of diabetes include retinopathy with potential loss of vision

(Rajala et al., 1998), nephropathy leading to renal failure (Strippoli et al., 2003), peripheral

neuropathy with risk of foot ulcers (Valensi et al., 1997), amputations (Dangelser et al.,

2003), and charcot joints (Leeet al, 2003), and autonomic neuropathy causing

gastrointestinal (Nishida et al., 2004), genitourinary (Goswami et al., 2000), and

cardiovascular symptoms (Turner et al., 1998), and sexual dysfunction (Morano, 2003).

patients with diabetes have an increased incidence of atherosclerotic cardiovascular

(Eastman et al., 1997), peripheral arterial and cerebrovascular disease (Stratton et al., 2000).

Hypertension and abnormalities of lipoprotein metabolism (Klein et al., 1993) and

periodontal disease are often found in people with diabetes (Emrich et al., 1991; Nelson et

al., 1990). The emotional and social impact of diabetes and the demands of therapy may

cause significant psychological dysfunction in patients and families (Meadows et al., 2000).

1.2.7. Diagnosis:

Diagnostic criteria (American Diabetic Association, 2004): Refer to Appendix I.

However, the diagnostic criteria of the American Diabetic Association (ADA) varies from

World Health Organization (WHO) criteria, as the former advocates abandoning the oral

glucose tolerance test (OGTT) because of high variability and relative complexity of OGTT

(Garcia-Webb & Bonser, 1981) whereas WHO strongly recommends the retention of OGTT

(Alberti & Zimmet, 1998). Under the WHO diagnostic criteria (Albert! & Zimmet, 1998),


                                               9
                                                                           Literature Review



6.1 mmol/lit is considered as the fasting and 7.8 mmol/lit as 2 hour cut-off for normal

glucose tolerance (NGT), and 2 hour values between 7.8 and < 11.1 mmol/ lit for impaired

glucose tolerance (IGT). Impaired fasting glycemia is established by FPG between 6.1 and

< 7.0 mmol/lit together with 2 hour PG < 7.8 mmol/lit. Diabetes is diagnosed if either FPG

> 7.0 mmol/lit or 2 hour PG > 11.1 mmol/lit (Albert! & Zimmet, 1998).

1.2.8. Management:

Patients with a diagnosis of diabetes should have a complete medical record and physical

examination. The purposes of this history and physical examination are to determine the

type of diabetes, current therapy, alcohol use, and behavioral health issues, as well as to

screen for the presence of diabetes related complications. It is essential that medication and

medical nutrition therapy should be continued without interruption upon entry as a hiatus in

either medication or appropriate nutrition may lead to either severe hypo or hyperglycemia

that can rapidly progress to irreversible complication, or even death.

Management Flan:

Glycaemic control is fundamental to the management of diabetes. A management plan to

achieve normal or near normal glycaemia with an HbAiC goal of less than 7% should be

developed for diabetes management at the time of initial medical evaluation. Goals should

be individualized and less stringent treatment goals may be appropriate for patients with a

history of severe hypoglycemia, patients with limited life expectancies, elderly adults and

individuals with co-morbid conditions (American Diabetic Association, 2004). Diabetes

self-management education should be an integral component of management.

Nutrition and food management:

Nutrition counseling and menu planning are an integral part of multidisciplinary approach

to diabetes management. People with diabetes should receive individualized medical

nutrition therapy (MNT) as needed to achieve treatment goals, preferably provided by


                                              10
                                                                           Literature Review



dietitian familiar with the components of MNT for persons with diabetes. Educating the

patient about how carbohydrates and food choices directly affect diabetes control is the first

step in facilitating self-management (American Diabetic Association, 2004). The earliest

and most cost-effective means to facilitate good outcomes in patients with diabetes is

instituting a heart healthy diet as the master menu (Krauss et al, 2000). In some individuals

with diabetes, adequate glycaemic control can be achieved through weight reduction,

exercise, and or oral glucose lowering agents (Eriksson & Lindgarde, 1991). These

individuals therefore do not require insulin. Other individuals who have some residual

insulin secretion but require exogenous insulin for adequate glycaemic control can survive

without it. Individuals with extensive p-cell destruction and therefore no residual insulin

secretion require insulin for survival. The use of insulin or oral medications may necessitate

snacks in order to avoid hypoglycemia. Timing of meals and snacks must be coordinated

with medication administration as needed to minimize the risk of hypoglycemia. The

severity of the metabolic abnormality can progress, regress, or stay the same. Thus the

degree of hyperglycemia reflects the severity of the underlying metabolic process and its

treatment more than the nature of the process itself.

Drug management:

Individual patient care may require short, medium and long acting insulin and various

classes of oral medications, e.g., insulin secretagogues, biguanides, a- glucosidase

inhibitors, and thiazolidinediones may be necessary for current diabetic management

(American Diabetic Association, 2004). Patients at all levels should have access to

medication at dosing frequencies that are consistent with their treatment plan and medical

condition. Medical department nurses should determine whether patients have the necessary

skills and responsible behavior to be allowed self-administration and the degree of

supervision necessary. When needed this should be a part of patient education. In the past,


                                              11
                                                                         Literature Review



the recommendation that regular insulin be injected 30-45min before meals presented a

significant problem when "lock downs" or other disruptions to the normal schedule of

meals and medications occurred. The use of multiple dose insulin regimens using rapid

acting analogs can decrease the disruption caused by such changes in schedule.

Self- management education:

Self-management education is the cornerstone of treatment for all people with diabetes.

Individuals with diabetes who learn self-management skills and make life style changes can

more effectively manage their diabetes and avoid or delay complications associated with

diabetes (Mensing et al., 2004). The unique circumstances of the patient should be

considered while still providing the greatest extent possible, the elements of the "National

Standards of Diabetes Self Management" (Table: 2).

Table 2: Major components of diabetes self-management education

Survival skills                              Daily management issues                       |
                                                                                           |
   •    Hypo or hyperglycemia                     *   Disease process
   •    Sick day management                       *   Nutritional management
   •    Medication                                •   Physical activity
   •    Monitoring                                *   Medications
   •    Foot care                                 •   Monitoring
                                                  •   Acute complications
                                                  •   Risk reduction
                                                  •   Goal setting or problem solving
                                                  •   Psychological adjustment
                                                  •   Preconception care or pregnancy or
                                                      gestational diabetes management


Survival skills should be addressed as soon as possible, other aspects of education may be

provided as part of an ongoing education program.




                                             12
                                                                           Literature Review



1.3. Diabetes and Oral diseases

1.3.1. Xerostomia and Parotid swelling:

Saliva protects and maintains the integrity of the oral mucous membrane by providing

lubrication during mastication and swallowing of food, it facilitates clear speech, as well as

normal perception of taste and soft tissue repair (Fox et al, 1985; Melvin, 1991; Sreebny &

Valdini, 1987). Saliva has direct antibacterial, antiviral, and antifungal activity (Sreebny &

Valdini, 1987). The buffer capacity of saliva is crucial for maintenance of optimal oral pH

and tooth integrity (Tenovuo, 1997). Impaired salivary flow rate and altered composition of

saliva may increase susceptibility to caries, periodontal disease, and oral mucosal lesions

(Ben Aryeh et al., 1993). In type-2 diabetes, high prevalence of mouth dryness, oral

Candida infections and swelling of parotid glands has been reported ( Mandel, 1980; Narhi

et al., 1996). Salivary flow rates are often found to be significantly reduced in type-2

diabetics (Newrick et al., 1991). In addition, significant increase in the concentrations of a

number of protein components were found in the diabetics, specifically lactoferrin,

myeloperoxidase, and salivary peroxidase. These increased concentrations of proteins may

suggest disease specific effects or increased leakage of proteins through basement

membranes affected by diabetes may be responsible for the elevated concentrations of

certain proteins (Dodds et al, 2000).

1.3.2. Candidiasis:

Diminished salivary flow may be conducive to opportunistic microorganisms, such as

Candida albicans. Indeed, there are more clinical Candida infections in diabetic patients

than non-diabetic individuals (Darwazeh et al., 1990; Lamey et al., 1988). A high blood

glucose level has been shown to associate with candidiasis (Hill et al, 1989) and a high

salivary glucose level with high salivary yeast counts (Karjalainen et al., 1996). Diabetic

patients colonized with Candida have higher salivary glucose levels than non-colonized


                                              13
                                                                           Literature Review



patients (Darwazeh et al., 1991). However, diabetes has not been shown to associate with

denture stomatitis (Phelan & Levin, 1986), and metabolic control has not been found to

have any significance concerning candidiasis (Bartholomew et al, 1987) or candidal load

(Willis et al., 1999).

1.3.3. Lichen Plan us & Leukoplakia:

The association between diabetes and oral lichen planus is conflicting both in relation to the

prevalence of diabetes in oral lichen planus (Silverman et al., 1985), and the prevalence of

oral lichen planus in diabetics (Petrou-Amerikanou et al., 1998). The association between

diabetes and lichen planus is based on immunological changes observed in both diseases

with respect to type-1 diabetes (Nerup et al., 1978). There may be a decreased glucose

tolerance in oral lichen planus patients (Lundstrom, 1983). However this observation was

not noted by others (Bussell et al., 1979). The prevalence of oral lichen planus in type-1

diabetic patients is 5.76% and in type-2 diabetics it is 2.83% (Petrou-Amerikanou et al.,

1998). The higher prevalence in type-1 diabetics could be due to auto immune phenomena

and T cell immune responses observed in both type-1 diabetics and oral lichen planus

patients respectively (Petrou-Amerikanou et al., 1998). Diminished salivary flow and the

atrophic oral mucosa may promote the development of leukoplakia and other precancerous

lesions or conditions (Rodriguez-Perez & Banoczy, 1982). The prevalence of oral

leukoplakia is 6.2% as compared to 2.2% in healthy patients (Albrecht et al, 1992).

Leukoplakia and oral lichen planus showed highest occurrence in the second year of

established diabetes and their prevalence is higher among insulin treated diabetics possibly

suggesting an association with insulin therapy (Albrecht et al., 1992).

1.3.4. Dental Caries:

Diabetic patients have more fillings (Albrecht et al., 1988) and more dental caries (Jones et

al, 1992) than non-diabetic patients. On the contrary, diabetic patients have been shown to


                                              14
                                                                            Literature Review



have lower active dental caries levels (Albrecht et al., 1988). Further, no differences have

been found in the caries level (Bacic et al., 1989) or the root caries level (Lin et al., 1999;

Tavares et al., 1991) between diabetic and non-diabetic patients. Poor metabolic control

appears to associate with dental caries (Jones et al., 1992; Narhi et al., 1996) but this was

not found by (Collin et al., 1998). Reasons for the elevated dental caries level in some

diabetic patients have been due to alterations in composition of saliva (Ben Aryeh et al.,

1993). Diabetics with a longer duration of diabetes had more manifest caries lesions than

non diabetics (Sandberg et al., 2000).

1.3.5. Delayed wound healing:

Wound healing is an interactive process that is greatly compromised in diabetics. The

altered wound healing in diabetes could be due to altered cellular, metabolic and

biochemical factors. The underlying macro-vascular (Shimomura & Spiro, 1987) and

micro-vascular pathology leads to impaired wound healing (Jaap et al., 1995).

Hyperglycemia may increase the available nutrients for bacteria and may also impair local

defenses (Kamal et al., 1996). Hyperglycemia also leads to production of pathologic

byproducts such as advanced glycosylation end products (AGEs) (Brownlee et al., 1988).

Impaired production of the growth factors or increased destruction of these may also alter

wound healing (Greenhalgh, 1996).

1.3.6. Periodontal diseases:

Periodontal disease has been considered as a sixth complication of diabetes (Loe, 1993) and

diabetes mellitus is considered as risk factor for periodontal disease (Salvi et al., 1997).

However, the association between diabetes and periodontal disease is complex and

controversial as the evidence has been advanced both for (Kawamura et al., 1998) (Table: 3)

and against (Hayden & Buckley, 1989; Hove & Stallard, 1970) (Table: 4) the association

between diabetes and periodontal disease. Emerging evidence portrayed the association as


                                              15
                                                                          Literature Review



bi-directional (Grossi, 2001; Grossi & Genco, 1998) unlike the previously thought

unidirectional association (Soskolne, 1998) in which the severe periodontits is considered as

a risk of poor glycemic control (Taylor et al., 1996). The association between these two

complex diseases can be explained by two similar but distinct pathologic pathways, a direct

causal association in which the consequences of diabetes act as modifiers of periodontal

disease expression (Yalda et al, 1994) or alternatively a common pathologic defect which

results in a host susceptible to either or both diseases.

The prevalence of diabetes in patients with periodontitis is double (12.5%) that seen in non-

periodontitis patient (6.3%) (Soskolne & Klinger, 2001), even though no difference is

detected in the number of etiologic factors or in the degree of gingival changes between the

diabetic and control groups. However patients with poorly controlled diabetes suffer more

from gingival bleeding than those with good or moderate control (Ervasti et al., 1985).

Calculus and poor metabolic control were thought to be the best predictors for probing

depth; patients with poor metabolic control and calculus has a higher prevalence of and

more extensive periodontal pockets than well or moderately controlled diabetics. Further

metabolic control is less important in terms of association with attachment loss in the

absence of calculus.

whereas age and number of teeth were significant variables for attachment loss (Oliver &

Tervonen, 1993). Good or moderate control of disease is attributed to patient cooperation.

Patients with well controlled diabetes might also be more cooperative regarding their oral

health care habits and dental care (Tervonen & Karjalainen, 1997). Clinical attachment loss

is more severe in diabetics compared to non-diabetics. Diabetics with poorly controlled

diabetes experience greater attachment loss compared to well controlled diabetics (Novaes

Jnr et al., 1996). Diabetic men have poorer periodontal status than non-diabetic men

(Bridges et al., 1996). Diabetic women have poorer periodontal status than non-diabetic


                                                16
                                                                          Literature Review



women (Cohen et al., 1970). Further, diabetic patients aged 55-74 have more severe

periodontal disease than patients aged 45-54 and 75-90 and comparable age matched non

diabetics (Tsai et al, 2002).

A long duration of diabetes is considered as a risk factor for periodontitis (Ainamo &

Ainamo, 1996). An association between longer duration of diabetes and severity of

attachment loss has been observed (Belting, 1964; Glavind et al., 1969). This correlation is

similar to that of other complications of diabetes such as retinopathy (Glavind et al., 1969)

and vascular disease (Al Delaimy et al., 2004). Contrary to this, an association between

duration of diabetes and periodontal and gingival status is not established (Alpagot et al,

2001; Bridges et al., 1996).




                                             17
     Table 3: Evidence for association between diabetes and periodontal disease

     S.    Authors           Study design                         Periodontal measures                  Observations
     No
     1     Belting et al.,   Cross-sectional study design with        1 . Russell ' s periodontal index 1. The severity of periodontal disease is
           1964              control group                                                                 greater in diabetic compared to control
                             Experimental group (Diabetics): 78                                            group.
                             Control group: 79                                                          2. As the degree of calculus increased, the
                             Age range: 20-89                                                              severity of periodontal disease increased


     2     Cohen et al.5 2 year longitudinal observation              2. Periodontal disease index      1 . Diabetics had more gingival involvement,
           1970          with control group. Experimental             3. Gingival score                     greater loss of attachment than non-
                         group (Diabetics): 21. Control               4. Soft & Hard deposit score          diabetics
                         group: 18. Age range: 18-35                                                    2. Soft deposits were significantly less in
                                                                                                            diabetics and no differences in amount of
                                                                                                            hard deposits.
     3     Emrich et al.,    Cross-sectional study design with         1.   Probing attachment loss     1 . Probing attachment loss is greater in
           1991              control group                            2.    Calculus index                  diabetics compared to non-diabetics
oo                           Study population : 1,342                  3.   Plaque index                2. Sub-gingival calculus increased through
                             Age range: > Syears                      4.    Gingival index,                 diabetes and age.
                                                                  All the   parameters on six index     3. The plaque index is higher in diabetics
                                                                  teeth                                     compared to control group.
                                                                                                        4. Gingival bleeding showed no age
                                                                                                            association and was very high in diabetics.

     4     Taylor et al.,    Longitudinal, observational study        1 . Clinical attachment loss by   1 . Poorly controlled diabetics have more
           1996              for 2 years.                                 Ramfjjord index teeth             clinical attachment and radiographic bone
                             Study population (Diabetics): 80         2. Panoramic radiographic             loss than well or moderately controlled
                             Age range: 18-67                             examination                       diabetics
                                                                                                                                                          CD

     5     Kawamura          Cross-sectional study design with        1.    Gingivitis index              1 . Mean gingivitis index is higher in          1
                                                                                                                                                          *-t
                                                                                                                                                          n>
           etal., 1998       control group                            2.    Oral hygiene index                diabetics than non diabetics
                             Experimental group (Diabetics): 108
                             Control group: 108
                             Age range: 28-69                    teeth
                                                                      3.
                                                                 All the
                                                                            Probing pocket depth
                                                                            parameters on six index
                                                                                                          2. Plaque and calculus levels are similar
                                                                                                              between groups
                                                                                                        Probing pocket depth is not significant ly
                                                                                                                                                          l
                                                                                                                                                          i
                                                                                                        different between groups, however attachment
                                                                                                        levels and numbers of missing teeth more in
                                                                                                        diabetics.
Table 4: Evidence against association between diabetes and periodontal disease

S.    Authors       Study design                         Periodontal measures                Observations
No
1     Hove&         Cross-sectional study design            1. Greene and Vermilion's        1. Increase in periodontal break down in
      Stallard,     with control group                         oral debris index                diabetics could be due to parallel
      1970          Experimental group (Diabetics):28       2. Ramfj ord gingival               increase in number of etiologic factors.
                    Control group: 16                          criteria                      2. Severity and duration of diabetes
                    Age range: 20- > 40 years                                                   appeared to have little effect on
                                                                                                oeriodontal disease
      Campbell.,    Cross-sectional study design            1. Russell's periodontal index      Within the two groups no difference could
      1972          with control group                      2. Greene and Vermilion's           be established between the periodontal
                    Control group: 102                         oral debris index                index and oral debris index
                    Age range: 17-39 years                                                      Tooth brushing frequency influenced the
                                                                                                periodontal index of both groups.

      Hayden &      Cross-sectional study design.         1. Data based on 3 sets of index   5. Severity of periodontal destruction is not
      Buckley,      Experimental group (Diabetics):          teeth (total 12).                  related to the clinical parameters of the
      1989          157                                   2. Plaque index                       diabetic condition, in particular to glycated
                    Age range: 8 -78 years                3. Gingivitis index                   hemoglobin percentage




      Kawamura et   Cross-sectional study design.          1.   Oral health behaviour        1. Severity of the periodontal disease is
      al.5 2001     Experimental group (Diabetics):        2.   Plaque index                    indirectly connected to diabetes through
                    102                                    3.   Calculus index                  health behaviours
                    Age range: < 70 years.                 4.   Gingivitis index
                    Incorporated health behaviours and     5.   Probing pocket depth
                                                                                                                                                CD


      Persson et    Cross-sectional study design           1. Clinical attachment loss          The number of remaining teeth did not           §
      al., 2003     with control group                     2. Panoramic radiographic            differ by diabetic status.
                    Experimental group (Diabetics):
                    131
                                                              examination                       Periodontitis is not a predominant
                                                                                                coexisting disease in older subjects with
                                                                                                                                                I
                                                                                                                                                i
                    Control group: 953                                                          diabetes
                    Age range: 60-75 years
                                                                            Literature Review



1.4. Periodontal diseases and associated risk factors

1.4.1. General health behaviour:

The optimal general health behaviour is defined as: not smoking, consuming fewer than ten

alcoholic drinks per week if male, and fewer than five if female, always wearing a seatbelt

in a car whether as a driver or as a passenger, participating at least three times a week in an

exercise activity such as brisk walking, aerobics, sports, or heavy house-work (Payne &

Locker, 1996). A common way to study the effects of health behaviour on disease is to

analyze bivariate relationships. A more advanced method is to study several behavioral

factors simultaneously. People with poor health behavior experienced more than 50%

greater mortality and occurrence of physical disability than those with good health

behaviour (Breslow & Breslow, 1993). The occurrence of disability is more closely related

to health habits than to social network (Breslow & Breslow, 1993). Healthy general health

behaviour measured in terms of smoking, alcohol consumption, eating breakfast, hours of

sleep, hours of work, physical exercise, nutritional balance, and mental stress are associated

with higher natural killer cell activity, which constitute the first line of defense (Kusaka et

al., 1992). The patterns of behaviours such as smoking, alcohol consumption, and physical

exercise in the context of appearance with respect to gender, age, employment status,

monthly family income, educational level, use of prescribed and non-prescribed

medications, perceived health status, and chronic illness varies among the subgroups of the

population in terms of their association with health and health behaviour (Dean et al., 1995).

Smokers seems to be inconsistent in their healthy behaviour, thus smoking might be a gate

way to and an indicator of unhealthy general health behaviour in general (Prattala et al.,

1994). There is a significant association between employment and health variables among

men aged over 40 years, whereas, an insignificant association between social or behavioural

variables and health variables among women below 40 years is noted. A healthier life style


                                              20
                                                                        Literature Review



and fewer micro vascular complications have been shown in diabetic males with higher

education (Chaturvedi et al., 1996). Among women, however the more educated perceived

themselves as healthier than those with less education (Dean et al, 1995). Unhealthy

behaviour is more common in the groups of less education, especially in the age groups of

30-39 years and among divorced subjects (Prattala et al., 1994). Lower social class or

educational level is associated with poor metabolic control and more risk factors for

cardiovascular disease and complications in type-2 diabetes (Connolly & Kesson, 1996).

Diabetic patients with poor metabolic control have a lower educational level, and report

more complications, nervous problems, sick leave days, disability pensions and lower level

of physical activity than patients in good or acceptable metabolic control (Larsson et al.,

1999). Along with educational level, diabetics with lower earning, bear a larger burden of

morbidity but use hospital care less (Bachmann et al., 2003). Females with diabetes and of

low social class faced a higher risk of mortality than did both non-diabetic females and

diabetic males of low social class (Nilsson et al., 1998).

1.4.1.1. Systemic factors:

Apart from the association between diabetes and periodontal disease, these two complex

and multi-factorial diseases are associated with other systemic diseases. The association

between diabetes and systemic factors has been evaluated in other sections of this

dissertation. The prevalence of systemic conditions that could effect the outcome of

periodontal therapy has been reported to vary between 39.9% (Rees & Brasher, 1974) and

52.5% (Peacock & Carson, 1995). An advancing age of periodontal patients has been found

to be significantly correlated to the prevalence of systemic disorders and a considerable

proportion of patients suffered from more than one disorder (Nery et al., 1987). Patients

suffering with cardiovascular disease were found to have significantly more lost teeth

(Lagervall et al., 2003). Periodontal disease and fewer teeth may be associated with


                                               21
                                                                           Literature Review



increased risk of ischemic stroke (Joshipura et al., 2003). Poor periodontal status is

considered as an important risk factor for infective endocarditis (Seymour et al., 2003).

Gingival inflammation correlates positively with the prevalence and magnitude of

bacteraernia (Guntheroth, 1984). However, periodontal bleeding per se is a poor indicator of

odontogenic bacteraemia. The link between dental procedures and infective endocarditis has

been extensively challenged (Strom et al, 1998; Van der Meer et al., 1992).

People with periodontal disease are more likely than the rest of the population to have

coronary heart disease, and vice versa (Seymour et al., 2003). A significant association was

found between dental infections and severe coronary atheromatosis (Atheroma is a plaque

consisting of lysed cells, cholesterol-ester crystals, lipid laden foam cells, and plasma

proteins such as fibrin and fibrinogen) in male patients. This association remained

significant and independent after adjusting age, sex, serum lipids, body mass index,

hypertension, smoking, and social class (Mattila et al., 1993; Mattila et al., 1995). However,

marginally significant (Danesh, 1999) and insignificant association has been observed

between CHD and periodontal disease (Hujoel et al., 2000).

There are broadly four etiopathogenic mechanisms which establish a possible association

between CHD and periodontal diseases. They consist of bacterial, hyperlipidaemia, genetic

and acute phase responses. The bacterial association is due to the ability of certain putative

periodontal pathogens such as Eikenella corrodens, P. gingivalis and Prevotella intermedia

to invade the human coronary artery endothelial cells and coronary artery smooth muscle

cells, along with oral sulcular epithelium (Dorn et al., 1999). The presence of P. gingivalis

in carotid and atheromatous plaques has been reported (Chiu, 1999; Haraszthy et al., 2000).

It is well established that lipid carrying lipoproteins are important risk factors for CAD;

periodontitis is associated with hyperlipidaemia (Cutler et al, 1999). Patients with

periodontitis had significantly higher serum triglycerides, total cholesterol and low density


                                             22
                                                                           Literature Review



lipoproteins than age and sex matched controls (Losche et al.5 2000). The mechanisms

associated with the periodontitis associated hyperlipidaemia are thought to reside with gram

negative infections that generate the release of various cytokines, in particular interleukin-

1(3 (DL-lp) and tumor necrosis factor alpha (TNF-a). Both cytokines can induce changes in

lipid metabolism that can result in a hyperlipidaemia (Doxey et al., 1998). However the

association has been shown to be weak (Wu et al., 2000).

There is evidence to suggest that IL-1 genetic polymorphisms are associated with an

increased susceptibility to severe generalized chronic periodontitis (Kornman et al., 1997).

Such polymorphisms are also associated with increased susceptibility to CAD (Francis et al,

1998), although further studies are required to confirm this association. Some of the most

convincing evidence to link periodontal disease with CAD derives from the process of the

bacterial plaque-induced inflammatory changes in the gingival connective tissues. The

bacterial challenge from the subgingival bio-film activates the hepatic acute phase response,

which results in raised white blood cell (WBC) counts, flbrinogen, C-reactive protein (CRP),

haptoglobin, a-1 antitrypsin and other inflammatory markers (Ebersole et al., 1997). CRP is

now considered an important marker for increased risk of CAD (Ridker et al., 1998). An

association has been established between periodontal disease and von Willebrand's factor

antigen (Mattila et al., 1989) which is a glycoprotein synthesized by vascular endothelial

cells and megakaryocytes. Levels of this antigen are high in patients with gram negative

infections of relevance to thrombogenesis. Endotoxin from such bacteria can induce the

release of von Willebrand's factor antigen from human endothelial cells (Schorer et al.,

1987). IL-1J3 and TNF-a secreted from hyperinflammatory monocytes can initiate platelet

adhesion and aggregation and promote the formation of lipid laden foam cells and

deposition of cholesterol in the intima (Marcus & Hajjar, 1993). Moreover cytokines

released from monocytes together with platelet derived growth factors (PDGF) will increase


                                             23
                                                                          Literature Review



smooth muscle cell proliferation leading to a thickening of the vessel wall which in turn

predisposes to atheroma formation. Monocytic activity is also influenced by low density

lipoproteins, up regulating the secretion IL-lp, and TNF-a (Jambou et al, 1993). These

findings present yet further evidence that might account for the association between

periodontal disease and CAD. Whilst some concerns have been expressed over the

association between periodontal disease and CAD, both diseases can form a syndrome,

referred as the periodontitis-atherosclerosis syndrome (Offenbacher et al., 1999). The recent

systemic review on the associations between periodontal disease and risk for atherosclerosis,

cardiovascular disease and stroke concluded that periodontal disease may be modestly

associated with atherosclerosis, myocardial infarction and cardiovascular disease, and called

for additional large scale longitudinal epidemiologic and interventional studies to validate

the association and to determine causality (Scannapieco et al., 2003).

1.4.1.2. Dietary & obesity factors:

Obesity is defined as excess body weight with an abnormally high proportion of body fat

(National Institutes of Health, 1998). Simple measures of weight for height that correlate

with body fat are used to identify overweight and obesity. The body mass index (BMI) has

gained widespread acceptance in the scientific community as the tool of choice in assessing

overweight and obesity in most adults (National Heart, Lung and Blood Institute Obesity

Education Initiative Expert Panel, 1998). Body mass index is defined as weight in

kilograms divided by height in meters squared. The World Health Organization (WHO)

committee and The National Institute of Health defined overweight as a BMI of 25 to 29.9

Kg/m2 and obesity as a BMI of 30 Kg/m2 or higher (National Heart, Lung and Blood

Institute Obesity Education Initiative Expert Panel, 1998; World Health Organization, 1998)

(Table: 5). BMI cutoffs are based on data showing that health risks increase beginning at a

BMI of 25 Kg/m2 (Troiano et al., 1996). However the observed risk in different Asian


                                             24
                                                                         Literature Review



populations varies from 22 Kg/m2 to 25 Kg/m 2 , for high risk it varies from 26 Kg/in2 to 31

Kg/m2 (WHO Expert Consultation, 2004). Body mass indices greater than 30 are

subdivided in to mild obesity, moderate obesity and extreme obesity (National Heart, Lung

and Blood Institute Obesity Education Initiative Expert Panel, 1998). The higher the obesity

subcategory, the higher the risk of morbidity from excessive weight and the more

aggressive treatments are indicated in the management of these individuals (National Heart,

Lung and Blood Institute Obesity Education Initiative Expert Panel, 1998). The age

standardized prevalence of overweight and obesity in Hong Kong are reported to be 30.5%

and 3.2% in men and 22.1% and 3.4% in women (Ko et al, 2001). However, the prevalence

of overweight and obesity in the working age group (20 to 65 years) was 28.98% and 3.55%

respectively, in the age group of over 60 years, the prevalence rates of overweight and

obesity are 36.31% and 4.81% respectively (Ko et al., 2001). The current increase in

prevalence of obesity has been associated with an increase in the prevalence of type-2

diabetes (Mokdad et al., 2001).

Table 5: classification of overweight and obesity

Classification                     BMI

Overweight                         25.0-29.9

Obesity                            > 30

Obesity, class 1                   30.0 - 34.9

Obesity, class 2                   35.0-39.9

Obesity, class 3                   > 40



Obesity is a known risk factor for type-2 diabetes, heart disease, stroke, hypertension,

osteoarthritis, sleep apnea, and some forms of cancer (National Task Force on the



                                            25
                                                                            Literature Review



Prevention and Treatment of Obesity, 2000). Overweight or obesity was the single most

important predictor of type-2 diabetes (Hu et al., 2001). According to recent surveys in

United States, the risk of diabetes increased approximately 9% with every Kilogram (Kg)

increase in self-reported weight (Mokdad et al, 2000), and 4.5% with every Kg increase in

measured weight (Ford et al., 1997). Duration of obesity was also positively associated with

the development of type-2 diabetes (Everhart et al., 1992). The exact nature of the

mechanism promoting type-2 diabetes in susceptible obese individuals has not yet been

identified. Obesity is associated with increase in insulin resistance (Albu & Pi-Sunyer,

1998). Obesity increases insulin resistance and glucose intolerance (Olefsky et al., 1982)

and   exacerbates   metabolic abnormalities present         in type-2    diabetes,   such     as

hyperinsulinemia, hyperglycemia and dyslipidemia (Albu & Pi-Sunyer, 1998). The cytokine

tumor necrosis factor a, whose expression in and secretion from adipose tissue is elevated in

obesity, may have a role in the insulin resistance of obesity and type-2 diabetes

(Hotamisligil & Spiegelman, 1994a). Adiponectin is another secretary product from adipose

tissue that may be involved in the development of type-2 diabetes in susceptible obese

individuals (Weyer et al, 2001). Obesity thus complicates the management of type 2

diabetes and makes it more difficult to treat pharmacologically (Albu & Raja-Khan, 2003).

An additional complication is that several of the agents used to treat type-2 diabetes, such as

insulin, sulphonylureas, and thiazolidenediones, promote weight gain (Albu & Pi-Sunyer,

1998; Albu & Raja-Khan, 2003). Obesity complicates the health risks of type-2 diabetes

and increases morbidity and mortality (Albu & Pi-Sunyer, 1998; Van Itallie, 1979). The

coexistence of obesity and diabetes, each as independent risk factor for hypertension, and

cardiovascular disease further increases the risk of developing these diseases (Albu & Pi-

Sunyer, 1998; Lew & Garfinkel, 1979).

Weight loss has beneficial effects on virtually every aspect of type-2 diabetes (Table: 6).


                                              26
                                                                          Literature Review



Table 6: Some benefits of weight loss in type-2 diabetes

Improved glycemic control (Henry et al., 1986).

Reduced fasting insulin (Amatruda et al., 1988).

Increased insulin sensitivity (Henry et al, 1986).

Improves insulin resistance (Laakso et al? 1988).

Reduced upper body adiposity (Markovic et al, 1998b).

Less atherogenic lipid profile (Grundy et al., 1999).

Decreased triglycerides (Grundy et al., 1999).

Increased high density lipoprotein cholesterol (Uusitupa et al., 1990).

Larger, less small, dense low density lipoprotein cholesterol particles (Markovic et al,

1998a).

Reduced blood pressure (Uusitupa et al., 1990).

Improved mortality (Gregg et al., 2003).



The initial management of obese patients who have type-2 diabetes traditionally involved

diet and weight loss (Hadden et al., 1986). Current nutritional principles of the American

Diabetic Association (ADA) advise that carbohydrates and monounsaturated fat should

together provide 60% to 70% of the caloric intake of patients who have type-2 diabetes

(Franz et al., 2003). Exercise helps to promote the long term maintenance of weight loss

(National Institutes of Health, 1998). Patients with type-2 diabetes treated in behavioral

weight loss programs, who reported the highest exercise levels lost the most weight and had

the largest reductions in HbAiC, independent of weight loss at 1 year from pretreatment

(Wing et al., 1988). In persons with type-2 diabetes, exercise improves cardiopulmonary



                                              27
                                                                            Literature Review



fitness, reduces blood glucose levels, improves insulin sensitivity, and reduces

cardiovascular risk by lowering blood pressure and improving dyslipidemia (Hamby et al,

2001). Behavioral therapy programs generally resulted in modest weight loss (Wing et al.,

1988).

According to NIH guidelines, the use of weight loss pharmacotherapy may be considered

for patients with type-2 diabetes with BMI of 27 or greater and those who failed to achieve

weight loss after at least 6 months of treatment with diet, exercise, and behavioral therapy

(National Institutes of Health, 1998). According to an NIH consensus developmental panel,

the use of bariatric surgery should only be considered in patients with type-2 diabetes with a

BMI of 35 or greater and those failed to achieve weight loss with more conservative

interventions (National Institutes of Health Consensus Development Conference Statement,

1992).

Obesity is significantly associated with periodontal disease through the pathway of insulin

resistance (Grossi & Ho, 2000). The pro-inflammatory cytokine, tumor necrosis factor alpha

produced from adipose tissues in obese patients is known to play a predominant role in

inducing insulin resistance (Nishimura & Murayama, 2001). Conditions associated with

obesity such as the metabolic syndrome may exacerbate periodontitis (Saito et al., 1998).

Obesity has a significant association with periodontitis in terms of BMI, body fat, and

maximum oxygen consumption (Saito et al., 1998; Saito et al, 2001; Wood et al, 2003).

However, the association is limited to younger obese population with increased prevalence

of periodontal disease (Al Zahrani et al., 2003; Sheiham et al., 2002) and periodontal

disease is positively associated with total cholesterol and low density lipoprotein cholesterol

(Katz et al., 2002).




                                              28
                                                                          Literature Review



1.4.1.3. Psychological factors:

Depression and psychosocial factors are considered as risk factors for both diabetes

(Kawakami et al., 1999) and periodontal disease (Moss et al., 1996). However the results

are inconclusive and contradictory (Persson et al., 2003; Talbot & Nouwen, 2000). Older

women seem to suffer more from depression than men (Minicuci et al., 2002). Although the

highest rates of depression are found among people under the age of 45, older adults are

more likely to be prescribed antidepressants (Patten et al., 2001). Prolonged negative events

may disturb the optimal functioning of host defense, consequently individuals experiencing

stress have the potential to develop chronic diseases (Clarke & Hirsch, 1995). An

underlying bio-behavioural mechanism of stress impact to progression of periodontal

disease has been suggested to act through two pathways (Melnick et al., 1988; Meyer, 1989).

Stress may activate several neuroendocrine systems including the hypothalamic-pituitary-

adrenal axis and the sympathetic nervous system leading to a reduced potential of the host

defense (Breivik, 1996) or affect the development of the disease through lifestyle factors

such as smoking (Preber & Bergstrom, 1990). Increased work and psychological stress is

associated with poor oral health status (Deinzer et al., 2001; Marcenes & Sheiham, 1992),

while stress maybe associated with increased caries and relaxation has an anti-caries effect

(Morse et al, 1982). The psychosocial measures of stress associated with financial strain

and distress manifest as depression are associated with severe periodontal disease in the

absence of adequate coping behavior, suggesting that the effects of stress on periodontal

disease can be moderated by adequate coping behaviors (Genco et al., 1999). Psychological

stress is also associated with resistance to periodontal treatment (Axtelius et al., 1998),

whereas depression is associated with tooth loss and chronic conditions associated with pain

(Persson et al., 2003).




                                             29
                                                                             Literature Review



1.4.2. Oral health behaviour:

The optimal oral health behaviour is considered as visiting a dentist at least once a year for

an examination rather than for a dental problem, at least daily tooth brushing, using an inter-

dental device such as a flossing daily, wooden tooth pick once or more per day, no snacking

between meals, and consuming no more than one cariogenic food a day (Payne & Locker,

1996). Physical activity is positively associated with tooth brushing, while alcohol

consumption and smoking correlated negatively (Rajala et al, 1980). The frequency of

tooth brushing is negatively correlated with sugar consumption among adolescents (Rajala

et al., 1980) and is a predictive indicator of general health behaviour (Tada & Matsukubo,

2003) whereas dental visiting habit has a weaker association with general life style (Sakki et

al., 1998). However, the frequency of tooth brushing is not an isolated behaviour but a part

of comprehensive health behaviour (Schou et al., 1990). Good oral hygiene habits are

positively associated with healthy food consumption, use of vitamins and regular physical

exercise among adolescents (Nutbeam et al., 1989). Non-smokers are more likely to visit

the dentist than smokers (Attwood et al., 1993). The association between physical exercise

and dental visiting behaviours is not established (Attwood et al,, 1993).

Poor oral health behaviour, specifically in combination with periodontal disease increases

the risk of occurrence of coronary heart disease (CHD) (Emingil et al., 2000; Montebugnoli

et al., 2004; Noack et al, 2001), however the results are inconsistent and inconclusive

(Hujoel et al, 2001; Joshipura et al., 1996; Mattila et al., 2000). The inconsistency in results

may be due to differences in age, sex of the subjects in the studies, the differences in

describing CHD, and in the variety of measures that have been used to describe the oral

health status, suggesting that the role of dental infections as a coronary risk factor could

vary according to the characteristics of the populations studies (Mattila et al., 2000).




                                              30
                                                                            Literature Review



Oral hygiene instructions were able exert a positive effect on fasting blood glucose levels

(FBGL), gingival crevicular fluid volume (GCF), community periodontal index of treatment

needs (CPITN), and plaque index (PII) (Almas et al, 2003). Mechanical (non-surgical)

periodontal treatment with and without antibiotics is also able to reduce the glycated

hemoglobin levels in the blood (Grossi et al., 1997; Rodrigues et al., 2003). Surgical

treatment responses in diabetics were no different to those in age and sex matched non

diabetics (Westfelt et al., 1996).

1.4.3. Inflammatory factors:

The cytokine, tumor necrosis factor alpha (TNF-a), is involved in the development of

obesity linked insulin resistance (Hotamisligil & Spiegelman, 1994b) by inhibiting tyrosine

kinase activity at insulin receptor (Hotamisligil et al., 1993). Phosphorylation of the insulin

receptor by this tyrosine kinase is known to be a cardinal step in the post-receptor events

that follow the binding of insulin to its receptor (Hotamisligil et al, 1994) and interferes

with the insulin signaling cascade (Hotamisligil et al, 1996). In diabetes mellitus, TNF-a

production was found to be increased (Lechleitner et al., 2002; Pickup et al., 2000; Zykova

et al., 2000), and TNF-a plasma levels seems to be positively associated to metabolic

control (Nilsson et al., 1998). High levels of TNF-a in patients with insulin resistance are

maybe due to high levels of fasting insulin (Mishima et al, 2001). The production and

activity of TNF-a is modulated by several oral anti-diabetic agents (Desfaits et al., 1998).

Beside these relationships between TNF-a, metabolic control, and anti-diabetic therapy,

ageing seems to be associated with an increase in TNF-a plasma levels (Taha et al., 2000).

This increase in TNF-a levels with aging maybe due to age associated increase in

percentage of body fat (Garthwaite et al., 1986). The levels of TNF-a decrease with the

weight loss (Dandona et al., 1998).




                                              31
                                                                         Literature Review



More recently, the cause and effect relation between pro-inflammatory cytokines such as

interleukin-1 (IL-1), TNF-a and periodontal tissue loss has been established (Delima et al.,

2001, Graves et al., 1998) The cellular source of serum TNF-a in periodontal diseases

include, monocytes, polymorphonuclear leukocytes, fibroblasts, epithelial cells, endothelial

cells, and osteoblasts. Once critical levels of pro-inflammatory cytokines production are

reached, a physiologic process becomes a pathologic response (Assuma et al, 1998). The

increased TNF-a in turn may exacerbate preexisting periodontal condition by stimulating

fibroblasts to synthesize matrix degrading enzymes (Brenner et al., 1989) or by stimulating

osteoclasts to activate bone resorption (Kobayashi et al., 2000). TNF-a can also induce

expression of other mediators that amplify or sustain inflammatory responses such as

prostaglandins, and the production of lytic enzymes, and can also enhance bacterial killing

and phagocytic activity (Pfizenmaier et al., 1996) and over production of TNF-a (Delima et

al., 2001) and synergistic action with DL-1 can enhance bone resorption (Stashenko et al.,

1987). Successful periodontal management decreases circulating TNF-a (Iwamoto et al,

2001). Additionally, the reduction in circulating TNF-a is correlated with an improvement

in metabolic control of diabetes possibly mediated through an improvement in insulin

resistance (Grossi et al, 1997; Iwamoto et al., 2001).

1.4.4 Conclusion:

By-and-large, the inconsistency and controversy with respect to the association between

diabetes and periodontal disease may be due to differences in metabolic control, duration of

diabetes and age and sex differences between different study populations from the diabetic

point of view and from the periodontal point of view, compliance of the patients, variations

in examination strategy and variations in study designs, and bias resulting subsequently

from the general point of view.




                                              32
                 Clinical Study




   Part II
Clinical study




      33
                                                                             Clinical study



Part II: Clinical study
2.1. Scientific rationale of the study

2.1.1. Aim:

The aim of the present study is to assess the associations between diabetes mellitus and

periodontal disease status through selected general and oral health behaviour factors and

inflammatory factors (TNF-alpha levels in the serum of the blood), and In addition, to test

the validity of recently proposed hypothetical model for associations between diabetes and

periodontal disease incorporating behavioural, metabolic and inflammatory factors.

2.1.2. Objectives:

The objectives of this study are as follows:

1) To assess the association between concurrent metabolic control of type-2 diabetes and

periodontal status as the hypothetical model suggests.

Health behaviour factors:

A total of 13 variables selected included; six behavioural components including general

health behaviour (GHB), perceived fatigue (PF), diet control (DC), regular diet (RD),

Hiroshima university dental behaviour inventory (HU-DBI), distress; and nine dental or

medical components including fasting plasma blood glucose (FBG), glycated hemoglobin

(HbAlc), body mass index (BMI) as medical components, TNF-a as inflammatory

component, debris index (DI), calculus index (CI), gingivitis index (GI), probing depth

(PD) and probing attachment loss (PAL) as dental components.




                                               34
                                                                           Clinical study



2.1.3. Hypothesis:

The hypothesized model was constructed based on the data previously published
Fig. 1:

Conceptual framework:




                                           35
                                                                          Clinical study



Null hypothesis:

1. General health behaviour (GHB) is not associated with oral health behaviour,

   diet behaviour, distress.

2. Perceived fatigue (PF) is not associated with diet behaviour and oral health

   behaviour.

3. Diet behaviour (DB) is not associated with metabolic control, obesity, oral

   debris and perceived fatigue.

4. Oral health behaviour (OHB) is not associated with general health behaviour,

   oral debris and calculus

5. Obesity is not associated with perceived fatigue, metabolic control, and serum

   TNF-alpha levels.

6. Oral debris is not associated with calculus and periodontal status.

7. Calculus is not associated with periodontal status.

8. Metabolic control is not associated with serum TNF-alpha levels and

   periodontal status.

9. Serum TNF-alpha levels are not associated with metabolic control and

   periodontal status.

10. Periodontal status is not associated with diabetes, serum TNF-alpha levels and
   distress.




                                         36
                                                                                Clinical study



2.2. Materials and methods
2.2.1. Study Design:

The study was of cross-sectional design with a convenient sample frame of 208. Chinese

type-2 diabetes mellitus subjects attending Tung Wah Eastern Hospital (TWEH) were

invited to participate in the study. The recruitment period was from 19th June 2003 to 20th

April 2004. An estimated sample size of at least 200 subjects is required to secure an

adequate sample power for the hypothesized model testing (Fig. 1). The protocol had been

approved by the Ethics Committee, Faculty of Dentistry, University of Hong Kong and

Tung Wah Eastern Hospital. Prior verbal and written consent has been obtained during the

inclusion of the subjects for this study (Appendix III). Randomization of the sample was not

considered instead sampling strategy was designed based on age, gender and degree of

metabolic control as it has been reported previously that periodontal status in type-2

diabetic population varies in association with age, gender (Tsai et al., 2002) and metabolic

status (Novaes Jnr et al., 1996). The following criteria had been adopted for subject

selection.

2.2.2. Inclusion and exclusion criteria:

Inclusion criteria:

    *   Chinese type-2 diabetes mellitus subjects within the age group of 40-70.

    *   Subjects with at least minimum of one tooth per sextant.

    *   Selection strategy included the equal spread of subjects between gender, age group

        (40-50, 51-60, 61-70) and diabetic control (good control, fair control, poor control).

Exclusion criteria:

All the subjects with the following conditions have been excluded from the study:

    *   Pregnancy.

    *   Smokers.


                                              37
                                                                               Clinical study



   •   Subjects who had received antimicrobial therapy in the past four months

   •   Subjects who had received periodontal treatment in the past one year.

   •   Subjects having a history of other systemic conditions such as, myocardial infarction,

       rheumatic fever, cardiac valvular defect etc, which may require prophylactic

       antibiotics for periodontal examination.

   •   Subjects suffering from severe neurological disorders affecting the mental state

       hence the accuracy of the questionnaire data.

Data collection:

The study population consisted of 101 male and 107 females The age range was 40 to 70

years. Data collection consisted of both clinical and behavioural or subjective parameters.

The periodontal clinical parameters included oral hygiene index, gingivitis index, probing

pocket depth and probing attachment levels. In addition medical clinical parameters such as

fasting blood glucose, glycated hemoglobin levels, serum TNF-a levels and body mass

index were measured. The data for behavioural or subject level parameters were collected

by means of assisted personal interviewed structural questionnaires.

2.2.3. Assessment of variables:

2.2.3.1. Oral health parameters:

Recruited patients were subjected to a periodontal examination using the William 14W

periodontal probe from Dentsply Ash® (Dentsply, U.K). Oral hygiene status was assessed

according to Greene and Vermillion Debris index (DI) and Calculus index (CI) (Greene &

Vermillion, 1960). The gingival status was assessed using the Gingivitis Index (GI)

(Jackson, 1965) as a measure of severity of gingival condition. In addition, periodontal

status was assessed by measuring full mouth probing pocket depth (PPD) and probing

attachment level (PAL) (Appendix I).



                                             38
                                                                               Clinical study



2.2.3.2. Metabolic and general health:

Additional clinical (medical) information was collected including fasting plasma blood

glucose (FBS), glycated hemoglobin (HbAiC) and body mass index (BMI) and TNF-alpha

(Appendix I). Fasting plasma glucose and glycated hemoglobin levels were obtained by

drawing blood from antecubital vein and were assessed by commercially available kits.

Fasting plasma glucose levels were assessed by Roche Cobas Integra®400 (Roche

diagnostics, Stuttgart, Germany) and glycated hemoglobin levels with the Variant™ II

hemoglobin testing system from Bio-rad® (Bio-rad laboratories, Hercules, CA, USA).

Additionally TNF-alpha levels in the serum were assessed with the Quantikine® TNF-alpha

high sensitivity immunoassay kit (R & D systems, Minneapolis, USA).

All the subjects were requested to complete structured questionnaires relating to general

health behaviour, diet behaviour and perceived fatigue employing the Japan railway health

questionnaire (JRHQ). JRHQ consists of 26 items covering 3 domains, general health

behaviour (GHB), diet behaviour (DB) and perceived fatigue (PF). The JRHQ was

subjected to factor analysis and those variables with the factor loading of more than 0.40

were only considered for final analysis. The JRHQ was subjected to factor analysis leading

to 6 items with the scale ranging 1-4 that define general health behaviour. The factor

loading of these items ranged from 0.42 to 0.74. These items refer to tend to do well for

health, concerned about lack of exercise, take care not to gain weight, eat lot of vegetables,

exercise and take meals at regular times. The minimum to maximum score range for general

health behaviour was 6-24. The lower total score represents the more strongly held

preventive health behaviour. The factor loading for 6 items (scale, 1-4) that define diet

behaviour ranged from 0.50 to 0.67. These items refer to often drink carbonated drinks and

juices, like to eat fatty meat, eat many sweet snacks as a child, drink medicated energy

drinks to restore your tiredness, like to eat cakes and sweets and how many times a week


                                             39
                                                                             Clinical study



eating out for dinner. The minimum to maximum score range for diet behaviour was 6-24.

The diet behaviour scores had been revised so that lower the total score represents more

strongly held preventive health behaviour. The factor loading for 4 items (scale, 1-4) that

define perceived fatigue ranged from 0.43 to 0.67. These items refer to satisfied with your

work, confident in maintaining health, do you sleep well and feeling that you tired easily.

The minimum to maximum score range for diet behaviour was 4-16. The lower total score

represents the more strongly held preventive health behaviour.

Oral health behaviour was assessed by employing Hiroshima University Dental Behaviour

Inventory (HU-BDI) comprising 20 items (scale, 0-1) that define oral health behaviour. The

HU-DBI has been shown to be internally consistent with a Cronbach's alpha of 0.76

(Kawamura et al, 2001). The minimum to maximum score range for oral health behaviour

is 0-20. The lower the total score represents the more strongly held preventive oral health

behaviour.

Distress was assessed by employing Beck's depression inventory (BDI) comprising of 21

items (scale, 0-3) that define that psychological status (Distress). The minimum to

maximum score range for psychological behaviour is 0-63. The lower total score represents

less distress. All these measures have demonstrated acceptable psychometric properties

(validity and reliability) in assessing general health behaviour, diet behaviour, perceived

fatigue, oral health behaviour and distress. All the questionnaires have undergone forward-

backwards translation in Chinese, Japanese and English for use in this study. Lower scores

of JRHQ, HU-DBI, BDI represents more strongly held preventive health behaviour

(Appendix II).

Data analysis:

Correlation coefficients were used to assess the associations between the selected health

behaviour, medical, metabolic and periodontal parameters. Non-parametric tests (Mann-


                                            40
                                                                              Clinical study



Whitney, Kruskal-Willis test) were used to assess the associations since the data was not

normally distributed. In addition to correlation coefficients, statistical analysis has been

performed to assess the variations among the selected health behaviour, medical, metabolic

and periodontal parameters for age, sex and metabolic control to identify the statistical

significance of those variables.

2.3. Results

2.3.1. Demographic characteristics:

The sample consisted of 208 nonsmoking type 2 diabetics aged 40-70 years having at least

one tooth per sextant attending the outpatient diabetic clinic of Tung Wah Eastern Hospital

during a 9-month period who were cross-sectionally examined 51% were female subjects.

The prevalence of severe periodontal disease based on the criteria of having at least two

sites with probing attachment loss of 6mm or more was 70.6% (Tsai et al, 2002).

2.3.2. Hypothesis testing:

The overall distribution of the data showed that they were not normally distributed. Hence

non-parametric tests were used for statistical analysis. The Japan railway health

questionnaire comprising of 26 items has been subjected to factor analysis. The factor

loadings for these items lead to 3 behavioural components, general health behaviour,

perceived fatigue and diet behaviour. The 3 behavioural components have been distributed

as follows.

Table 7. Varimax rotated factor structure of the Japan railway health questionnaire

         Item Descriptions*                               Eigenvalues**         Loadings***
  F1     General health behaviour (GHB)                      2.69
  6      tend to do good for health                                                 0.74
  7      Concerned about lack of exercise                                           0.56
  11     take care not to gain weight                                               0.44
  12     eat a lot of vegetables                                                    0.42
  13     move body briskly                                                          0.63
  14     take your meals at regular times                                           0.56



                                            41
                                                                                         Clinical study



  F2      Diet behaviour (DB)                                          2.01
  2       often drink carbonated drinks and juice                                                 0.67
  4       like to eat fatty meat                                                                  0.50
   5      eat many sweet snacks as a child                                                        0.53
          drink medicated energy drinks to restore your
   8      tiredness                                                                               0.55
  10      like to eat cakes and sweets                                                            0.53
  24      how many times a week eating out for dinner                                             0.51

  F 3 Perceived fatigue (PF)                                1.66
  19    Satisfied with your work                                                  0.43
  20    Confident in maintaining health                                           0.59
  21    do you sleep well                                                         0.60
  23    feel that you get tired easily                                           -0.67
*The original was written in Japanese. The questionnaire was translated into English and

Chinese and then back to Japanese for verification by bi or tri-linguists.

**Factors with Eigen values >1.66 were only selected.

***Item loadings >0.40 (irrespective of the sign) were included.

The overall distributions of the variables are summarized in table 8:

Table 8: Overall distributions of the variables

Abbreviations used in the tables: BMI=Bocty Mass Index, BDI=Beck's Depression Inventory, FBS=Fa$tmg

Blood Sugar, HbA lc=Glycated Hemoglobin, PPD=Probmg Pocket Depth, PAL=Probing Attachment Level;

N- Number of subjects, IQR=Inter Quartile Range, S.D. =Stan dard Deviation, S.R=Standard Error.

           Variables             N Mean Median Minimum Maximum                  Range     IQR     S.D     S.E
 General Health Behaviour       208 11.11 11.00  6.00   23.00                    17.00    4,00    3.28    0.23
 Perceived Fatigue              208 8.69  8.00   4.00    16.00                   12.00    3.00    2.21    0.15
 Diet Behaviour                 208 11.33 11.00  6.00   20.00                    14.00    5.00    3.01    0.21
 BMI (Kg/M2)                    208 25.36 24.9   18.16  36.89                    18.74    4.66    3.72    0.26
 BDI                            208 8.71  7.00   0.00   36.00                   36.00     7.82    6.65    0.46
 FBS (mmol/1)                   208 8.22  7.65   3.60    19.50                  15.90     2.88    2.92    0.20
 HbAlc (%)                      208 7.59  7.25   5.30    17.70                   12.40    1.78    1.62    0.11
 TNF-alpha (pg/ml)              208 0.65  0.63   0.03    3.47                    3.44     0.41    0.42    0.03
 Oral Health Behaviour          208 7.64  8.00    1.00   15.00                  14.00     3.00    2.54    0.18
 Debris Index                   208 4.89  4.71   0.92    10.17                   9.25     1.67    1.54    0.11
 Calculus Index                 208 4.56  4.50   0,50    10.17                   9.67     2.50    1.78    0.12
 Oral Hygiene Index             208 9.45  9.08    1.58  20.08                    18.50    4.31    3.18    0.22
 Gingival status                208 1.72   1.76  0.01    3.44                    3.43     0.79    0.55    0.04
 PPD (mm)                       208  2.47 2.36   0.03    6.10                    6.07     0.96    0.91    0.06
 PAL (mm)                       208 3.49  3.43   0.03    7.13                    7.10     1.43    1.27    0.09



                                                  42
                                                                             Clinical study



All the variables are divided between good control (< 7% HbAiC), fair control (7.0%-8.2%

HbAiC) and poor control diabetes (> 8.3% HbAiC) as shown in tables 9-11:

Table 9: Distribution of the variables according to good diabetic status

          Variables         N Mean     Median   Minimum    Maximum      Range   IQR    S.D    S.E
General Health Behaviour    91 10.56    10.00     6.00      23.00       17.00   5.00   3.41   0.36
Perceived Fatigue           91 8.75      8.00     4.00       16.00      12.00   3.00   2.28   0.24
Diet Behaviour              91 11.04    11.00     6.00       19.00      13.00   4.00   2.89   0.30
BMI (Kg/M2)                 91 25.16    24.72     18.55     36.10       17.55   5.17   3.87   0.41
BDI                         91 8.99     7.00      0.00      30.00       30.00   8.00   6.33   0.66
FBS (mmol/1)                91 6.68      6.50     4.00       15.00      11.00   1.80   1.67   0.18
HbAlc (%)                   91 6.44      6.40     5.30       9.00        3.70   0.70   0.65   0.07
TNF-alpha (pg/ml)           91 0.63      0.62     0.03       3.47        3.44   0.42   0.44   0.05
Oral Health Behaviour       91 7.38      8.00     2.00       14.00      12.00   4.00   2.33   0.24
Debris Index                91 5.13      4.75      1.08      10.17       9.08   1.50   1.64   0.17
Calculus Index              91 4.56      4.33     0.50       10.17       9.67   2.58   1.85   0.19
Oral Hygiene Index          91 9.68      9.25      1.58     20.08       18.50   4.17   3.31   0.35
Gingival status             91 1.63      1.67     0.21       3.44        3.23   0.79   0.54   0.06
PPD (mm)                    91 2.34      2.17     0.33       6.10        5.77   1.18   0.96   0.10
PAL (mm)                    91 3.27      3.15     0.46       6.64        6.18   1.49   1.21   0.13


Table 10: Distribution of variables according to fair diabetic status

           Variables        N Mean Median       Minimum    Maximum      Range IQR      SJ)    S.E
 General Health Behaviour   68 11.13 11.00        6.00       18.00       12.00 4.00    3.03   0.37
 Perceived Fatigue          68 8.53   8.00        5.00       14.00       9.00  3.00    1.99   0.24
 Diet Behaviour             68 11.35 12.00        6.00       19.00       13.00 5.00    2.98   0.36
 BMI (Kg/M2)                68 25.27 24.61        19.83     33.98        14.16 4.56    3.50   0.42
 BDI                        68 8.18   6.50        1.00      36.00       35.00 6.00     6.72   0.81
 FBS (mmol/1)               68  8.30  8.20        3.60       15.00       11.40 1.80    1.79   0.22
 HbAlc (%)                  68 7.55   7.50        7.10       8.20         1.10 0.50    0.33   0.04
 TNF-alpha (pg/ml)          68 0.65   0.66        0.03        1.89        1.86 0.32    0.35   0.04
 Oral Health Behaviour      68 7.94   7.00        3.00       15.00       12.00 4.00    2.59   0.31
 Debris Index               68 4.68   4.42        1.75       9.83        8.08  1.31    1.49   0.18
 Calculus Index             68 4.57   4.46        1.75       9.75        8.00 2.27     1.76   0.21
 Oral Hygiene Index         68 9.25   8.92        3.50       18.67       15.17 3.21    3.16   0.38
 Gingival status            68 L77    1.75        0.95       3.34        2.39 0.70     0.56   0.07
 PPD (mm)                   68 2.49   2.48        0.11       5.16        5.05 0.76     0.89   0.11
 PAL (mm)                   68 3.57   3.54        0.12       6.94        6.82  1.44    1.35   0.16




                                           43
                                                                                        Clinical study



Table 11: Distribution of the variables according to poor diabetic status

           Variables         N     Mean Median       Minimum    Maximum    7    , ,qs     IOR     S.D      S.E
General Health Behaviour     49    12.10 12.00         6.00      23.00     17.00          4.50    3 .20    0.46
Perceived Fatigue            49    8.82  8.00          4.00      14.00     10.00          3.00    2 .39    0.34
Diet Behaviour               49    11.82    12.00      6.00      20.00     14.00          5.00    3.26     0.47
             2
BMI (Kg/M )                  49    25.84    25.35     18.16      36.89     18.74          4 .79   3 .77    0.54
BBI                          49    8.94     7.00      LOO        36.00     35.00          7.00    7,.22    1.03
FBS (mmol/1)                 49    10.99    9.80      5.20       19.50     14.30          5.45    3,.83    0.55
HbAlc (%)                    49    9.78     9.20      8.30       17.70      9.40          1.70    1,.72    0.25
TNF-alpha (pg/ml)            49    0.69     0.67      0.03        2.41     2.38           0 .54   0..49    0.07
Oral Health Behaviour        49    7.69     8.00       LOO       14.00     13.00          4 .00   2..84    0.41
Debris Index                 49    4.73     4.67      0.92        7.33     6.42           2.17    1.38     0.20
 Calculus Index              49    4.56     4.67       LOO        7.92     6.92           2 .92   1,.69    0.24
 Oral Hygiene Index          49    9.29     9.67       1.92      15.25     13.33          5.33    3.00     0.43
 Gingival status             49    1.84     1.89       0.01       3.23     3.22           0.50    0.56     0.08
PPD (mm)                     49    2.68     2.61       0.03      5.70      5.67           0.81    0..82    0.12
PAL (mm)                     49    3.80     3.68       0.03      7.13      7.10           1.40    L.21     0.17


All the variables are divided between gender (Male & Female) as shown in tables 12-13:


Table 12: Distribution of variables according to gender (Male)

           Variables         N     Mean     Median    Minimum   Maximum        Range       *QR      SJ)      S.E
 General Health Behaviour    101    10.81    10.00      6.00       23.00       17.00       4.50     3.12     0.31
Perceived Fatigue            101    8.43     8.00       4.00       16.00       12.00       3.00     2.25     0.22
 Diet Behaviour              101    12.05    12.00      6.00       20.00       14.00       4.00     3.05     0.30
             2                                                                  17.9       4.32     3.59
 BMI (Kg/M )                 101    25.45    24.82       19        36.89                                     0.36
 BDI                         101    7.89      7.00      LOO        36.00       35.00       6.50     5.97     0.59
 FBS (mmol/1)                101    8.39      7.90      4.10       18.80       14.70       2.80     3.00     0.30
 HbAlc (%)                   101    7.62      7.30      5.30       17.70       12.40       1.65     1.82     0.18
 TNF-alpha (pg/ml)           101    0.66     0.66       0.03       2.41        2.38        0.41     0.42     0.04
 Oral Health Behaviour       101    7.97      8.00      4.00       14.00       10.00       3.00     2.13     0.21
 Debris Index                101    4.85     4.67       0.92       9.92         9.00       1.88     1.62     0.16
 Calculus Index              101    4.68     4.58       0.50       10.17        9.67       2.50     1.87     0.19
 Oral Hygiene Index          101    9.53     9.33       1.58      20.08        18.50       4.38     3.39     0.34
 Gingival status             101    1.79     1.84       0.21       3.44        3.23        0.68     0.56     0.06
PPD (mm)                     101    2.57     2.53       0.21       6.10        5.89        0.95     0,92     0.09
 PAL (mm)                    101    3.64     3.53       0.22       7.13        6.91        1.47     0.92     0.12




                                              44
                                                                               Clinical study



Table 13: Distribution of variables according to gender (Female)

          Variables          N Mean Median         Minimum   Maximum   Range     IQR    S.D     S.E
General Health Behaviour    107 11.39 11.00          6.00     23.00    17.00     5.00   3.42    0.33
Perceived Fatigue           107 8.94   8.00          4.00     14.00    10.00     3.00   2.15    0.21
Diet Behaviour              107 10.64 10.00          6.00     19.00    13.00     3.00   2.82    0.27
BMI (Kg/M2)                 107 25.27 24.98         18.16     35.74    17.58     4.92   3.87    0.37
BDI                         107 9.49   8.00          0.00     36.00    36.00     8.00   7.18    0.69
FBS (mmol/1)                107 8.07  7.60           3.60     19.50    15.90     2.90   2.85    0.28
HbAlc (%)                   107   7.56     7.20      5.70     12.80    7.10      1.80   1.41    0.14
TNF-alpha (pg/ml)           107   0.65     0.61      0.03      3.47    3.44      0.44   0.43    0.04
Oral Health Behaviour       107   7.33     7.00      LOO      15.00    14.00     4.00   2.85    0.28
Debris Index                107   4.93     4.75      2.33     10.17    7.83      1.67   1.46    0.14
Calculus Index              107   4.45     4.33      1.83      9.83     8.00     2.25   1.68    0.16
 Oral Hygiene Index         107    9.37    9.00      4.42     19.67    15.25     3.67   2.99    0.29
Gingival status             107    1.66    1.69      0.01      3.00    2.99      0.81   0.54    0.05
PPD (mm)                    107   2.37     2.28      0.03      5.17    5.14      1.03   0.90    0.09
PAL (mm)                    107   3.36     3.26      0.03      6.94    6.91      1.45   1.32    0.13



All the variables are divided between age groups (40-50,51-60,61-70) as shown in tables

14-16:

Table 14: Distribution of variable according to age group (40-50)

          Variables          N    Mean    Median   Minimum   Maximum   Range     *QR    S.D     S.E
General Health Behaviour     57   11.56    12.00     6.00     23.00    17.00     4.00   3.52    0.47
Perceived Fatigue            57   8.91     8.00      4.00      14.00   10.00     3.00   2.25    0.30
Diet Behaviour               57   12.47    12.00     7.00      19.00   12.00     5.00   2.73    0.36
BMI (Kg/M2)                  57   25.43    24.45     19,94    36.89    16.95     4.06   3.74    0.50
BDI                          57   6.77     5.00      0.00     22.00    22.00     7.00   4.95    0.66
 FBS (mmol/1)                57   8.48     7.90      3.60      16.90   13.30     3.00   2.90    0.38
 HbAlc (%)                   57   7.70     7.40      5.40      11.40    6.00     1.75   1.38    0.18
 TNF-alpha (pg/ml)           57   0.79     0.73      0.03      2.41     2.38     0.51   0.51    0.07
 Oral Health Behaviour       57   8.04     8.00      LOO       15.00   14.00     4.00   2.49    0.33
 Debris Index                57   4.69     4.58      0.92      7.42     6.50     1.58   1.38    0.18
 Calculus Index              57   4.37     4.25      0.50      7.92     7.42     2.67   1.76    0.23
 Oral Hygiene Index          57   9.05     8.83      1.58      15.25   13.67     4.67   2.99    0.40
 Gingival status             57   1.72     1.74      0.21      3.34     3.13     0.87   0.63    0.08
 PPD (mm)                    57   2.51     2.31      0.21      5.70     5.49     L01    1.03    0.14
 PAL (mm)                    57   3.41     3.06      0.22      7.13     6.91     1.65   1.42    0.19




                                             45
                                                                               Clinical study



Table 15: Distribution of variable according to age group (51-60)

           Variables        N    Mean    Median   Minimum   Maximum   Range      IOR    S.D     S.E
General Health Behaviour    68 11.00      11.00     6.00      17.00    11.00     4.00   2.74    0.33
Perceived Fatigue           68 9.00        9.00     5.00      16.00   11.00      3.00   2.36    0.29
Diet Behaviour              68 11.62      12.00     6.00      20.00   14.00      5.00   3.39    0.41
BMI (Kg/M2)                 68 25.51      24.93    18.16      36.10   17.95      5.59   4.07    0.49
BDI                         68 10.06      7.50     LOO        36.00   35.00      8.00   7.96    0.97
FBS (mmol/1)                68 7.86       7.60     4.70       17.00   12.30      3.30   2.45    0.30
HbAlc (%)                   68 7.52       7.30     5.30       17.70   12.40      2.15   1.78    0.22
 TNF-alpha (pg/ml)          68 0.62       0.64     0.03        1.64     1.61     0.37   0.30    0.04
 Oral Health Behaviour      68 7.91       8.00     3.00       14.00    11.00     3.75   2.53    0.31
 Debris Index               68 5.03       4.83     2.58       9.83     7.25      1.56   1.51    0.18
 Calculus Index             68 4.63       4.58     1.67       9.83     8.17      2.35   1.76    0.21
 Oral Hygiene Index         68 9.66       9.79      4.25      19.67    15.42     3.44   3.12    0.38
 Gingival status            68 1.73       1.77      0.75      3.44     2.69      0.80   0.58    0.07
 PPD (mm)                   68 2.38       2.30      0.11      6.10     5.99      0.81   0.96    0.12
 PAL (mm)                   68 3.36       3.37      0.12      6.64     6.52      1.43   1.28    0.15


Table 16: Distribution of variable according to age group (61-70)

           Variables        N    Mean    Median   Minimum   Maximum   Range      IQR    S.D      S.E
 General Health Behaviour   83   10.89    10.00     6.00     23.00    17.00      4.00   3.52     0.39
 Perceived Fatigue          83   8.29     8.00      4.00     13.00    9.00       2.00   2.00     0.22
 Diet Behaviour             83   10.30    10.00     6.00     18.00    12.00      4.00   2.52     0.28
             2                                               34,19    15.25      4.62   3.44     0.38
 BMI (Kg/M )                83   25.18    25.12    18.95
 BDI                        83    8.94     8.00     1.00     30.00    29.00      7.00   6.24     0.69
 FBS (mmol/1)               83    8.34     7.60    4.00      19.50    15.50      2.60   3.27     0.36
 HbAlc (%)                  83    7.58     7.20     5.80      13.90   8.10       1.50   1.65     0.18
 TNF-alpha (pg/ml)          83    0.58     0.60     0.03      3.47    3.44       0.41   0.43     0.05
 Oral Health Behaviour      83    7.14     7.00     LOO       14.00   13.00      4.00   2.53     0.28
 Debris Index               83    4.91     4.67     1.75      10.17   8.42       1.92   1.66     0.18
 Calculus Index             83    4.63     4.42     1.75     10.17    8.42       2.67   1.81     0.20
 Oral Hygiene Index         83    9.54     9.08     3.50     20.08    16.58      4.83   3.37     0.37
 Gingival status            83    1.73     1.77     0.01     3.02     3.01       0.66   0.48     0.05
 PPD (mm)                   83    2.52     2.53     0.30     5.17     5.14       0.88   0.78     0.09
 PAL (mm)                   83    3.66     3.61     0.03      6.31    6.28       1.44   1.14     0.12




                                             46
                                                                             Clinical study



2.3.2.1. General health behaviour:

The general health behaviour was calculated from Japan railway health questionnaire

(JRHQ). The lower the total score, the better the general health behaviour. There was no

significant difference in general health behaviour between male and female genders

(p=0.070) (Mann-Whitney test), among the different age groups (p=0.546) and also among

the different diabetic status groups (p=0.120) (Kruskal-Wallis test).

General health behaviour was significantly associated (weak) with psychological behaviour

(Distress or BDI) (r=0.150, pO.05, Fig 1), however there was no significant association

between general health behaviour and oral health behaviour (r=-0.073, /?=0.294), general

health behaviour and perceived fatigue (r=0.130, /?=O.062), general health behaviour and

diet behaviour (r=0.083,/?=0.233).

Figure 1:




                        0            10           20           30       40

                        Distress
General health behaviour was also significantly associated with diabetic status (HbAlc)

(r=0.239,/K0.01, Fig 2) and FBS (r=0.169,/K0.01, Fig 3)




                                             47
                                a
                                OQ
                                                                a
                                                                <w*
                                I




     General health behaviour        General health behaviour




oo




                                                                      o
                                                                      II
                                                                               Clinical study



2.3.2.2. Diet behaviour:

The diet behaviour was calculated from Japan railway health questionnaire (JORHQ). The

diet behaviour score has been revised so that lower the total score the better the diet

behaviour. There was no significant difference in diet behaviour among the different age

groups (p=0.131) and also among the different diabetic status groups 0=0.750) (Kruskal-

Wallis test), however females showed better diet behaviour (p<0.001, Fig 4).

Diet behaviour was also significantly associated with oral health behaviour (HU-DBI,

r=0.192, pO.Ol, Fig 5) and debris index (r=-0.144, /K0.05, Fig 6) however the associations

are considered to be weak.

Figure 4:
                     221
                     20
                     18
                     16
                     14
                     12
                     10
                      8
               .8    6
                cd
                     4
                     2
                     0
                      N=             107                   101

                                      F                    M

                          Gender

There was no significant association between diet behaviour and perceived fatigue (r

0.011,/7=0.879) and obesity (r=0.0523jp=0.455) (Spearman's correlation).




                                            49
                 Clinical study



Figure 5:




Figure 6:




            50
                                                                               Clinical study



2.3.23. Perceived fatigue:

Perceived fatigue was calculated from Japan railway health questionnaire (JRHQ). The

lower the total score, the least the perceived fatigue. There was no significant difference in

perceived fatigue between male and female genders 0=0.134) (Mann-Whitney test), among

the different age groups 0=0.384) and also among the different diabetic status groups (p=

0.849) (Kruskal-Wallis test).

Perceived fatigue was associated with oral health behaviour (r=0.140, /K0.05, Fig 7) and

distress (r=0.301,p<0.01, Fig 8) however the associations were considered weak.


Figure 7:




Figure 8:




                         1


                                Distress




                                             51
                                                                           Clinical study



There was no significant association between perceived fatigue and obesity (r=-0.024,

/?=0.735) (Spearman's correlation).

2.3.2.4. Oral health behaviour:

The oral health behaviour was calculated from Hiroshima University Dental Behaviour

Inventory (HU-DBI). The lower the total score, the better the oral health behaviour. Oral

health behaviour was associated with mean probing pocket depth (r=0.188,/K0.01, Fig 9),

mean probing attachment level (r=0.186, /K0.01, Fig 10) and mean gingival status (GI,

r==0.149,/K0.05,Figll).



Figure 9:




                   0      1       2   3     4     5      6

                    Mean PPD




                                           52
                             a
                             CVQ                          CTQ

                                                          1



     Oral health behaviour         Oml health behaviour




u>




                                                                o
                                                                o
                                                                          Clinical study


2.3.2.5. Obesity:

There was no significant difference in obesity between male and female gender (p=0.681)

(Mann-Whitney test), among the different age groups (p=0.949) and also among the

different diabetic status groups (p=0.427) (Kruskal-Wallis test).

There was no significant association between body mass index (obesity) and metabolic

control (r=0.093, /?=0.184) and TNF-alpha levels in the serum (r=-0.031, ^=0.660)

(Spearman's correlation).

2.3.2.6. Psychological behaviour (Distress):

The psychological behaviour was calculated from Beck Depression Inventory (BDI). The

higher the total score, the higher the levels of depression. There was no significant

difference with psychological behaviour (Distress) between male & female genders (p=

0.126) (Mann-Whitney test) and also among the different diabetic status groups (p=0.514)

(Kruskal-Wallis test), however significant difference was observed among different age

groups with 40-50 year age group showing the better psychological behaviour than 51-60 &

61-70 year age groups (p< 0.022, Fig 12).

Figure 12:

                         40




                         30




                         20



                    .§ 10
                    ~O
                    •6
                                          57
                                      40 to 49    50 to 59   60 to 69

                              Age Group




                                                 54
                                                                            Clinical study



Psychological behaviour was significantly associated (weak) with oral health behaviour (r=

0.201, /K0.01, Fig 13), however there was no significant association between psychological

behaviour and mean probing pocket depth (r=0.045, ^=0.523), mean probing attachment

level (r=0.016, /?=0.817) and mean gingival status (r=-0.053, /?=0.444) (Spearman's

correlation).

Figure 13:


                           40

                           35

                           30

                           25
                     s
                           20

                     -g
                     OsJ
                           15

                           10




                                Oral health behaviour



2.3.2.7. Oral hygiene status:

There was no significant difference in oral hygiene status between male and female genders

(p=0.544) (Mann-Whitney test), among the different age groups (p=0.631) and also among

the different diabetic status groups (p=0.647) (Kruskal-Wallis test).

Mean debris index was significantly associated with mean calculus index (r=0.827, /K0.01,

Fig 14). Oral hygiene status was significantly associated with mean probing pocket depth

(r=0.36, /K0.01, Fig 15), mean probing attachment level (r=0.327, /K0.01, Fig 16) and

mean gingival status (r=0.561,/K0.01, Fig 17) however the strength of the associations are

only weak to moderate.


                                                        55
                                                          Clinical study



Figure 14:

                  30




                  20




                  10
             x
             <D




                   o,
                                           10        20   30

                        Calculus Index

Figure 15:




                       Oral Hygine Index




                                                56
                                               Clinical study



Figure 16:




             0            10         20

             Oral Hygine Index


Figure 17:




                 Oral Hygine Index




                                          57
                                                                             Clinical study


2.3.2.8. Metabolic control:

Metabolic control (diabetic status, HbAlc) was significantly associated with mean probing

pocket depth (r=0.202, /X0.01, Fig 18), mean probing attachment level (r=0.180, /K0.01,

Fig 19) and mean gingival status (r=0.144,p<0.01, Fig 20). However, TNF-alpha levels in

the serum were not significantly associated with mean probing pocket depth, (r=0.134,

p=0.054), mean probing attachment level (r=0.131, /K0.060), mean gingival status

(r=0.Ill,p=Q. 110), obesity (r=-0.031,^=0.660) and diabetic status(r=0.015,/?=0.830).

There was also significant difference in the mean probing pocket depth, mean probing

attachment loss and mean gingival status between different diabetic status groups (Fig 21-

23). Significant difference was observed between good and poor diabetic status groups for

mean probing pocket depth (p<0.05), mean probing attachment loss 0<0.009) and mean

gingival status (p<0.001) (Kruskal-Wallis test) however no significant difference in mean

probing pocket depth, mean probing attachment loss and mean gingival status was observed

between good and fair control groups, and between fair and poor control groups.

Figure 18:




                                                                   16   18




                                            58
                                                                Clinical study


Figure 19:




                       HbAlc




Figure 20:




             O    .5
             03
             O


                           2   4   6    8   10   12   14   16   18

                       HbAlc




                                       59
             Clinical study


Figure 21:




Figure 22:
                                                                              Clinical study



Figure 23:




                            DM status


2.3.2.9. Serum TNF-alpha levels:

TNF-alpha levels in the serum are not significantly associated with mean probing pocket

depth (r=0.134, /?=0.054), mean probing attachment level (r=0.131, p=Q.Q6Q\ mean

gingival status (r=0.111,/7=0.110), obesity (r=M).0313jp=0.660) and diabetic status (r=0.015,

/?=0.830) (Spearman correlation), however significant association has been observed

between serum TNF-alpha levels and mean calculus index (r=0.1435jp<0.05, Fig 24).

Figure 24:
                                                                                        Clinical study



2.3.2.10. Missing teeth:

There was no significant association between number of missing teeth and diabetic status

(p=0.263) (Kruskal-Wallis Test), however there was particular trend of increase in number

of missing molars 0<0.766), missing premolars (p<0.592) and missing anteriors (p<0.167)

with increase in the level of glycated hemoglobin levels in the blood (diabetic status).

A long duration of diagnosed diabetes (more than 16 years) was significantly associated

with missing anterior teeth (/?<0.025, Fig 25), however the long duration of diabetes was not

significantly associated with missing molars (p=0.465) and premolars (p=O.617). The long

duration of the diabetes (more than 5 years) was also significantly associated with mean

probing pocket depth (/?<0.04, Fig 26), mean probing attachment level (p<0.01, Fig 27) and

mean gingival status (p<0.004, Fig 28).

Figure 25:




             GO
             00


                                 114            64           16             14

                           Less than 5 yrs   5-10 yrs     10-15yrs   More than 15 yrs

                     Years diagnosed as diabetic




                                                     62
                                                    Clinical study



Figure 26:




             Years of diabetes (under/above 5yrs)

Figure 27:




             Years of diabetes (under/above 5yrs)




                                       63
                                                    Clinical Study



Figure 28:




             Years of diabetes (under/above 5yrs)




                                       64
            Discussions and Conclusions




    Part III
Discussions and
  conclusions




       65
                                                                 Discussions and Conclusions



Part HI: Discussions and conclusions
3.1. Discussion of population and methods

3.1.1. Study population:

The main purpose of this clinical study was to assess the associations between health

behaviours, metabolic control, serum TNF-alpha levels and periodontal status in Chinese

type-2 diabetics. The total number of study population was 208, nonsmoking type-2

diabetics with at least one teeth per sextant, which was considered sufficient to assess the

associations between the study variables. The study design intended to have an equal spread

of subjects between the age, sex and metabolic control, however this could not be achieved

for the 40-50 year age and poor metabolic control groups. This could be due to the

possibility that 40-50 year age group is most likely to be in the work force and all the

examinations were done during the working days. The poor control patients are also

difficult as our efficient team of diabetologists converts the poor control into good control in

no time. The controversy between the associations between diabetes and periodontal disease

could be due the variations in the age, gender and metabolic control among the populations

studied (Tsai et al., 2002). In view of the this, the present study population was divided

between the age groups (40-50 years, 51-60 years, 61-70 years), genders and levels of

metabolic control (good control, fair control, poor control) to define the associations

between health behaviours, metabolic control, serum TNF-alpha levels and periodontal

status.

3.1.2. Self reporting and clinical examinations:

There may be doubts about the credibility of self reported answers to health behaviour items.

It has been proposed that self assessments may be very truthful in some items, while being

inaccurate in others. The inaccuracy may be due to forgetting or negligence or some

patients may give excessively positive answers to avoid guilt or and anxiety. Furthermore,


                                              66
                                                               Discussions and Conclusions



the current oral hygiene practice items only inquire about frequencies, while the quality of

behaviour cannot be measured. In view of the above, the present study followed the

stringent criteria in the process of collecting the questionnaire data. The questionnaire has

been translated from Japanese to Chinese and English and back and forth by the bi - and tri-

linguists. The HU-DBI has also shown to be internally consistent with Cronbach's

coefficient alpha = 0.76. In addition Japan railway health questionnaire (JRHQ) has been

subjected to factor analysis for the further analysis of general health behaviour, diet

behaviour, and perceived fatigue. The data for all the structured questionnaires has been

obtained with personal interview by a trained dental surgery assistant before the clinical

examination.

The oral clinical examination was performed by the one trained and calibrated examiner.

For the present data, the 95% limits of reproducibility ranged from -1.20 to 1.36. Metabolic

control and serum TNF-alpha levels were measured from the blood drawn on the day of the

examination. Commercially available kits were used to calculate the glycated hemoglobin

percentage, FBS and serum TNF-alpha levels in the blood. HbAlc as an indicator of level

of metabolic control is widely accepted (Gonen et al, 1977). Height and weight of the

subjects were measured using the routinely followed armamentarium in the general health

hospital.

3.2. Discussion of the results

3.2.1. Health behaviours:

3.2.1.1. General health behaviour and Distress:

The factor loading for 6 items that define general health behaviour ranged from 0.42 to

0.74. These items refer to; tend to do well for health, concerned about lack of exercise, take

care not to gain weight, eat lot of vegetables, move body briskly and take meals at regular




                                             67
                                                                Discussions and Conclusions



time. General health behaviour did not significantly vary between the different age groups,

genders and metabolic status.

The general health behaviour was significantly associated with distress and glycated

hemoglobin levels. It is rather interesting to observe the association between general health

behaviour and diabetes as the upcoming treatment modalities for diabetes includes general

health behavioural items such as tend to do good for health, exercise, take care not to gain

weight, eat lot of vegetables and take meals at regular time (Eriksson & Lindgarde, 1991).

The patients with poor general health behaviour are also highly distressed (Hellerstedt &

Jeffery, 1997; Moller et al, 1996). Diabetes by itself a distressing factor, diabetes coupled

with poor general health behaviour leads to distress. The general health behaviour

associated with distress and glycated hemoglobin levels explains its duel role and

complexity of multi-factorial diseases.

3.2.1.2. Diet behaviour:

The factor loading for 6 items that define diet behaviour ranged from 0.50 to 0.67. These

items refer to; often drink carbonated drinks and juices, like to eat fatty meat, eat many

sweet snacks as a child, drink medicated energy drinks to restore your tiredness, like to eat

cakes and sweets and how many times a week eating out for dinner. Diet behaviour was not

significantly varied between the different age groups and metabolic status however females

showed better diet behaviour than males. The components of diet behaviour undergo

progressive changes with age and gender. In this crossectional study females showed better

diet behaviour probably through their consciousness to not to gain weight. The influence of

Energy density (ED) of the diet, food volume (FV) and energy intake (El) by age and sex in

a healthy population reported that during adulthood, a significant trend towards decrease

was observed in El and ED. However, FV decreased significantly only in females (Marti-

Henneberg et al., 1999). These finding's are in line with our study.


                                              68
                                                                Discussions and Conclusions



Diet behaviour was significantly associated with oral health behaviour and debris index.

One possible reason for the association between diet behaviour and oral health behaviour is

patients with better diet behaviour are more determined to maintain better oral health.

However this clinical study failed to provide any association between diet behaviour and

perceived fatigue. A previous study investigated health behaviours, periodontal status in

Japanese type-2 diabetics showed the bidirectional association between diet behaviour and

perceived fatigue (Kawamura et al.5 2001). One possible reason for the difference could be

due to differences in the populations studied, Japanese versus Chinese. It is also reasonable

to suspect difference in the cultural and social behaviour of the Japanese population.

3.2.1.3. Perceived fatigue:

The factor loading for 4 items that define perceived fatigue ranged from 0,43 to 0.67. These

items refer to; satisfied with your work, confident in maintaining health, do you sleep well

and feeling that you tire easily. Perceived fatigue was not significantly varied between the

different age groups, genders and metabolic status groups.

Perceived fatigue was significantly associated with distress and oral health behaviour. This

may indicate that patients often felt stressed and tired more easily because of symptomatic

problems associated with diabetes, especially in patients with complications. A previously

published study (Dwyer, 1997) reported two bi-directional associations, one between

effective distress and social support and the second between perceived well-being and daily

distress. One of them was similar to that of our behavioural association between perceived

fatigue and distress.

Perceived fatigue was also associated with oral health behaviour. It is reasonable to suspect

that symptomatic problems associated with diabetes along with high levels of perceived

fatigue resulted in poor oral health behaviour. The associations between perceived fatigue

and distress and between the distress, perceived fatigue and oral health behaviour explain


                                              69
                                                               Discussions and Conclusions



the complex web of behavioural factors associated with multi-factorial diseases. It is

reasonable to argue that stress associated with diabetes might have influenced the perceived

fatigue along with oral health behaviour. Previously published studies (Deinzer et al., 2001;

Marcenes & Sheiham, 1992) strongly support the assumption that distress may induce

neglect of oral hygiene and increase of plaque accumulation through the changes in the oral

health behaviour.

3.2.1.4. Oral health behaviour:

The oral health behaviour was calculated from Hiroshima University Dental Behaviour

Inventory (HU-DBI) comprising 20 items dealing with various oral health behaviour

attitudes. HU-DBI was shown to be internally consistent with Cronbach's (coefficient)

alpha of 0.76. Oral health behaviour was significantly associated with mean probing pocket

depth, mean probing attachment level and gingival status. It is reasonable to assume that

good oral health behaviour has an impact on the periodontal status through good oral

hygiene habits as a previously published report suggested that physical activity was

positively correlated with tooth brushing (Rajala et al., 1980) and good oral hygiene habits

are positively associated with healthy food consumption and regular physical exercise

(Nutbeam et al., 1989). The interesting observation is virtual absence of correlation between

oral health behaviour and oral hygiene status which is rather interesting. However one

possible reason could be oral health behaviour represents a much bigger picture of the oral

health attitudes and perception of the problems posed rather than mere oral hygiene. It has

been previously reported that patients with well controlled diabetes might also be more

cooperative regarding their oral health care habits and dental care (Tervonen & Karjalainen,

1997).




                                              70
                                                               Discussions and Conclusions


3.2.2. Obesity:

The mean BMI of the observed population was 25.36±3.72 Kg/m2 which is well within the

range of WHO Expert Consultation report of health risk for the Asian population (WHO

Expert Consultation, 2004) and BMI of the Hong Kong Chinese diabetic population was

reported to be 25.7 Kg/m2 which is in line with the present study (Lee et al, 2002) however

no significant associations were observed between obesity and glycated hemoglobin levels

and serum TNF alpha levels. BMI is the only measure of obesity used in the analysis. It

was reported that multivariate genetic analysis using 3 indexes of obesity suggested that the

differences of genetic influences might reflect different etiologic associations with

cardiovascular disease, Type-2 diabetes, and essential hypertension, for which fat

distribution is the known risk factor (Cardon et al., 1994). Fatness variables such as

waist/hip ratio (WHR) and sub-scapular/triceps ratio (SSTR) should be included in our

analysis, then two or more observed variables could clarify the concept of obesity and its

association in diabetics. There was also no significant associations observed between

obesity and periodontal status (PPD, PAL, GI) which is in contrast to previously published

reports (Grossi & Ho, 2000) which is again could be due to employing only BMI as the

measure of obesity.

3.2.3. Metabolic control:

3.2.3.1. Serum TNF-alpha:

Serum TNF-alpha levels were not associated with obesity, diabetes or periodontal status.

However significant association has been observed between serum TNF-alpha levels and

calculus index. TNF-alpha, the pro-inflammatory cytokine secreted from macrophages,

leukocytes and adipocytes play a important role in the pathogenesis of periodontal disease

(Page et al., 1997) and diabetes (Pickup et al., 2000). The absence of associations between

the serum TNF-alpha and periodontal status, obesity and diabetes could be due to the low


                                             71
                                                                Discussions and Conclusions



prevalence of cytokine gene polymorphisms (Armitage et al., 2000) thereby reduced

secretion of the cytokine levels and also could be due to the fact serum TNF-alpha is

somewhat less potent than IL-1 in the pathogenesis of periodontal disease (Okada &

Murakami, 1998).

In the absence of significant associations between serum TNF-alpha and periodontal status,

obesity and diabetes, the association between serum TNF-alpha and calculus index is rather

difficult to explain and should be subjected for speculation.

3.2.3.2. Diabetic status:

In line with many previously published well designed clinical studies (Bridges et al, 1996;

Emrich et al., 1991; Kawamura et al., 1998; Taylor et al., 1996), in this clinical study

glycated hemoglobin levels in the blood were associated with mean probing pocket depth,

mean probing attachment level and mean gingival status. The direct causal association

between diabetes and periodontal disease could be due to the fact that consequences of the

diabetes (AGEs, etc.) act as modifiers periodontal disease expression As the diabetic control

was an important factor affecting the periodontal status, it seemed logical to divide the

study population based on diabetic control (glycated hemoglobin levels) (Tsai et al., 2002)

in to good control, fair control and poor control diabetics. In this clinical study all the

periodontal parameters were more severe in poorly controlled diabetics compared to good

control diabetics, which conforms to previously published reports (Oliver & Tervonen,

1993; Novaes Jnr et al., 1996). In a previously published study with a similar study design

(Kawamura et al., 2001) the absence of associations between mean probing pocket depth

and glycated hemoglobin levels could be due to partial mouth recording (index teeth) for

probing pocket depth and exclusion of the measurements of probing attachment level which

are considered as a important in diagnosis of the periodontal disease. It has also been

reported that the use of index teeth may result in underestimation of prevalence of early


                                              72
                                                                Discussions and Conclusions



periodontitis and overestimation of the extent of the condition (Eaton et al., 2001), whereas

full-mouth examination is more valid and reliable in estimating the severity of the

periodontal disease (Borges-Yanez et al., 2004).

3.2.3.3. Duration of diabetes:

In this clinical study, a long duration of diagnosed diabetes (more than 5 years) was

significantly associated with mean probing pocket depth, mean probing attachment levels

and mean gingival status which conforms to a previously published report (Glavind et al,

1969). That a long duration of diabetes has an effect on the periodontal condition may be

through the clustering effects of age associated factors along with status of diabetes.

However it is highly possible that diabetes was diagnosed after many years of its onset and

diabetes was well controlled and managed better after the diagnosis, in either case duration

of the diabetes has it own impact on the periodontal condition as the previously published

reports point out that well controlled diabetic patients do not differ significantly from non-

diabetic controls in terms of gingival inflammation or in terms of the course of pre-existing

periodontal disease (Novaes Jnr et al., 1991). A long duration of diagnosed diabetes (more

than 16 years) was also associated with missing anterior teeth. The higher number of

missing anterior teeth could also be due to the above explained associations between

diabetes and periodontal status.

3.2.4. Periodontal status:

In this clinical study periodontal status was significantly associated with; glycated

hemoglobin levels, oral health behaviour, debris index, calculus index, which explains

about the complex and multi-factorial nature of the periodontal disease onset and

progression (The American Academy of Periodontology, 2001).




                                              73
                                                                 Discussions and Conclusions



3.2.4.1. Probing pocket depth & Probing attachment level:

Mean probing pocket depth and mean probing attachment levels were significantly

associated with; oral health behaviour, debris index, calculus index (i.e. oral hygiene status),

glycated hemoglobin levels in the blood and duration of diabetes. The impact of oral health

behaviour on periodontal status were through ones ability in maintaining oral hygiene status

along with oral health attitudes and finally through their perception of oral health. The

impact of mere oral hygiene instructions and thereby further improving the oral health

behaviour, periodontal status and diabetic condition has been previously reported (Almas et

al., 2003). The better oral health behaviour may also improve the oral hygiene status which

is calculated from both debris and calculus index. Both the oral health behaviour, debris and

calculus index are significantly associated with mean probing pocket depth and mean

probing attachment level. However interestingly the present study failed to correlate the oral

health behaviour with oral hygiene status although both oral health behaviour and oral

hygiene levels are independently associated with periodontal status which explains that oral

health behaviour represents a much bigger picture of the oral health attitudes and perception

of the oral health rather than mere oral hygiene It further explains the complex nature of the

behavioural aspects of periodontal disease. This clinical study supports that better oral

health behaviour and oral hygiene status may help in maintaining healthy periodontal and

diabetic status.

In line with many previously published well-designed clinical studies (e g: Bridges et al.,

1996; Emrich et al., 1991; Kawamura et al., 1998; Taylor et al., 1996) in this study glycated

hemoglobin levels in the blood and duration of diabetes (more than 5 years) (Glavind et al,

1969) are significantly associated with mean probing pocket depth and mean probing

attachment level which explains a direct causal association in which the consequences of

diabetes act as modifiers of periodontal disease expression (Yalda et al., 1994).


                                               74
                                                                Discussions and Conclusions



3.2.42. Gingival status:

Mean gingival status was significantly associated with oral health behaviour, debris index,

calculus index (i.e. oral hygiene status), glycated hemoglobin levels in the blood and

duration of diabetes. Although Jackson's gingival index, debris and calculus index are

measures of the gingivitis and oral hygiene status in categorical representation, foil-mouth

mean scores are calculated to analyze the statistical associations between the variables to

keep the analysis as simple as possible. In line with a previously published report (Ervasti et

al., 1985), the poorly controlled diabetics demonstrated worse gingival status than the well

controlled diabetics.

3.2.5. Missing teeth:

The absence of control group hinders the comparison of missing teeth between the diabetics

and non-diabetics. Analysis of missing teeth with diabetic status did not reveal any

association between diabetic status and number of missing teeth, possibly due to the fact

that the inclusion criteria requires the presence of at least minimum of one teeth per sextant

which doesn't allow for accurate comparison of missing teeth among the different diabetic

status groups. However there is peculiar trend of increase in the number of missing teeth

with increase in the levels of glycated hemoglobin levels in the blood (poorly controlled

diabetic status). On the other hand a long duration of diabetes was significantly associated

with missing anterior teeth which support the notion that longer duration of diabetes leads to

more severe attachment loss (Glavind et al., 1969). It is reasonable to investigate further the

impact of duration of diabetes along with diabetic status as this clinical study correlates the

duration of diabetes with missing teeth along with a trend for more missing teeth with

poorly controlled diabetic status. The more missing anterior teeth with long duration of

diabetes could be due to clustering effects of age associated periodontal events (Genco,

1996), along with long duration of diabetes.


                                               75
                                                                Discussions and Conclusions



3.2.6. Associations between the variables tested and their relative significance:

The final model after the data analysis revealed the following significant associations:




                                                                                    General
health behavior




                                                                                     status




The current clinical study which followed a similar study design as (Kawamura et al., 2001)

demonstrated a different profile of associations between the variables investigated. The

variations could be simply due to the differences in the populations, Japanese and Chinese.

The most significant associations are:

    1. General health behaviour is significantly associated with distress and glycated

       hemoglobin levels.

   2. Perceived fatigue is significantly associated with distress and oral health behaviour.

   3. Diet behaviour is significantly associated with oral health behaviour and debris

       index.

   4. Oral health behaviour is significantly associated with mean probing pocket depth,

       mean probing attachment levels and mean gingival status.

    5. Distress is significantly associated with oral health behaviour




                                              76
                                                               Discussions and Conclusions



   6. Debris index is associated with calculus index, debris index and calculus index

       independently and together as oral hygiene status, is significantly associated with

       mean probing pocket depth, mean probing attachment level and mean gingival status.

   7. Glycated hemoglobin levels in the blood are significantly associated with mean

       probing pocket depth, mean probing attachment levels and mean gingival status

   8. Serum TNF-alpha levels are significantly associated with calculus index

   9. Gingival status was significantly associated with mean probing pocket depth and

       mean probing attachment levels.

Kawamura observations (Kawamura et al., 2001):

   1. General health behaviour was significantly associated with diet behaviour, perceived

       fatigue, debris index, calculus index and oral health behaviour.

   2. Perceived fatigue was significantly associated with regular diet

   3. Diet control was significantly associated with regular diet, BMI and glycated

       hemoglobin levels.

   4. Regular diet was significantly associated with calculus index and glycated

       hemoglobin levels.

   5. Oral health behaviour was significantly associated with calculus index.

   6. Debris index was significantly associated with calculus index

   7. Calculus index was significantly associated with mean gingival status and mean

       probing pocket depth

   8. Gingival status was significantly associated with mean probing pocket depth.

The current study was able to confirm some finding reported by the Kawamura. The most

significant of them are

    1. Debris index is significantly associated with calculus index.




                                             77
                                                               Discussions and Conclusions



    2. Calculus index is significantly associated with mean probing pocket depth and

        mean gingival status.

    3. Gingival status is significantly associated with mean probing pocket depth.

However, the current study demonstrated several significant unparallel findings from

Kawamura study. The most significant of these associations are:

   1. General health behaviour is significantly associated with distress and glycated

       hemoglobin levels. However Kawamura and coworkers couldn't find similar results

       possibly due to the fact that associations through health behaviours largely depend

       on life styles, cultural and social behaviour of the study population. The current

       study differs from the previous study in the observation of Chinese to Japanese. The

       current study also failed to demonstrate some associations shown by Kawamura and

       coworkers such as associations between general health behaviour with diet

       behaviour, perceived fatigue, debris index, calculus index with oral health behaviour,

       possibly due to the above explained reasons.

   2. Perceived fatigue is significantly associated with distress and oral health behaviour.

       Kawamura and coworkers observed associations between perceived fatigue and

       regular diet. The difference in number of subjects along with differences in the study

       populations might explain the differences in these observations.

   3. The factor analysis of Japan railway health questionnaire lead to 3 behavioural

       components in the current study (General health behaviour, perceived fatigue, diet

       behaviour) as compared to 4 (General health behaviour, perceived fatigue, diet

       behaviour, subdivided in to regular diet and diet control) demonstrated by

       Kawamura and coworkers. The diet behaviour is significantly associated with oral

       health behaviour and debris index whereas Kawamura and coworkers observed the

       association between diet control and regular diet, BMI and glycated hemoglobin


                                             78
                                                         Discussions and Conclusions



   levels. Regular diet was also significantly associated with calculus index and

   glycated hemoglobin levels. The difference in these observations could be due to the

   fact that factor analysis showed slight variation in the diet behaviour along with

   previously explained reasons such as differences in number of subjects and study

   populations.

4. Oral health behaviour demonstrated correlation with mean probing pocket depth,

   mean probing attachment levels and gingival status. Kawamura and coworkers could

   not find similar results, possibly due to better behaviour patterns of Japanese

   population or also possibly due to skewed results.

5. Associations between periodontal status and glycated hemoglobin levels shown in

   this study were not found by Kawamura and coworkers possibly due to partial

   mouth recording, absence of the measurements of probing attachment loss, which is

   the most important marker for periodontal disease. Also the current study examined

   208 type-2 diabetics compared to 102 observed by the previous study and any

   observational     study requires a high sample size to be able to demonstrate

   associations.

6. The debris index is correlated with mean probing pocket depth, mean attachment

   loss and gingival status. Kawamura and coworkers could not find similar

   associations possibly due to partial mouth recording, absence of the measurements

   of probing attachment loss which is the most important marker for periodontal

   disease, possibly due to patients brushing their teeth before the examination. Also

   the current study examined 208 type-2 diabetics compared to 102 examined in the

   previous study.

7. Kawamura and coworkers did not incorporate distress and serum TNF-alpha

   measurements in their study design. Distress levels as it has been shown to be an


                                         79
                                                                Discussions and Conclusions



       important risk factor for both diabetes (Kawakami et al, 1999) and periodontal

       disease (Moss et al., 1996).

3.2.7. Conclusions:

Overall, the following conclusions can be drawn from the current              cross-sectional

observational clinical study of Chinese type-2 diabetes patients:

    1. General health behaviour is significantly associated with distress and glycated

       hemoglobin levels

   2. Perceived fatigue is significantly associated with distress and oral health behaviour

   3. Diet behaviour is significantly positively associated with oral health behaviour and

       negatively with debris index

   4. Distress is significantly associated with oral health behaviour

   5. Oral health behaviour is significantly associated with mean probing pocket depth,

       mean probing attachment levels and gingival status

   6. Debris index is associated with calculus index, debris index and calculus index

       independently and together as oral hygiene status are significantly associated with

       mean probing pocket depth, mean probing attachment level and mean gingival status

   7. Glycated hemoglobin levels in the blood are significantly associated with mean

       probing pocket depth, mean probing attachment levels and mean gingival status

   8. Gingival status was significantly associated with mean probing pocket depth and

       mean probing attachment levels

   9. Serum TNF-alpha levels are significantly associated with calculus index

The conclusions drawn above explain the complex connectivity between the studied health

behaviours, diabetes and periodontal status. However the current study adds further

evidence that periodontal disease and diabetes are directly associated although health




                                              80
                                                              Discussions and Conclusions



behaviours which form a complex web of indirect associations between these two complex

and multi-factorial diseases.

The following indirect associations can be drawn from the present study:

    1. General health behaviour could be associated with periodontal status through

       metabolic control or through distress and oral health behaviour

   2. Diet behaviour may be associated with periodontal status through oral health

       behaviour and debris index

   3. Perceived fatigue may also be associated with periodontal status through distress

       and oral health behaviour

   4. Distress may be associated with periodontal status through oral health behaviour

    5. TNF-alpha could be associated with periodontal status through calculus index

These indirect associations should be considered equally as important as the direct

associations between different variables observed because both diabetes and periodontal

disease are considered as complex diseases and multi-factorial in nature. The delivery of

comprehensive health care and health education for Chinese type-2 diabetics with

periodontal disease should enhance the potential for disease control of both diabetes and

periodontal disease.




                                             81
           Appendix




Appendix




    82
                                                                              Appendix -1



                                     Appendix - 1

Diabetes mellitus:

Definition:

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting

from defects in insulin secretion, insulin action or both (American Diabetic Association,

2004; Guillausseau, 1997; Lebovitz, 2001;Rayburn, 1997; Sacks, 1997).

Normal Levels of Blood Glucose: A fasting glucose concentration 109 mg/dl (6.1mmol/lit)

has been chosen as the upper limit of normal. Although it is recognized as arbitrary, it is

near the level above which acute phase insulin secretion is lost in response to intravenous

administration of glucose, and is associated with a progressively greater risk of developing

micro and macro vascular complication (Guillausseau, 1997).

Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG)

The terms IGT and IFG refer to a metabolic stage intermediate between normal glucose

homeostasis and diabetes (Guillausseau, 1997; Rayburn, 1997)

IGT: This stage includes individuals with fasting plasma glucose levels equal to greater

than 110 mg/dl (6.1mmol/lit) but less than 126 mg/dl (7.0mmol/lit)

IFG: This term is used to refer to fasting plasma glucose level equal to or greater than 110

mg/dl (6.1mmol/lit) but less than 140 mg/dl (7.8mmol/lit).

In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but

rather risk factors for future diabetes. These can be observed as intermediate stages in the

disease progress of diabetes mellitus.




                                             83
                                                                                 Appendix -1



Criteria:

Three ways to diagnose diabetes mellitus are possible, and each must be confirmed, on a

subsequent day, by any one of the three methods (American Diabetic Association, 2004)

    1) Symptoms of diabetes plus casual plasma glucose concentration equal to or greater

        than 200 mg/ dl (ll.lmmol/lit). 'Casual' is defined as any time of day without

        regard to time since last meal. The classical symptoms of diabetes include polyuria,

        polydipsia, polyphagia, weight loss, and blurred vision.

    2) Fasting plasma glucose equal to or grater than 126 mg/ dl (7.0mmol/lit) Fasting is

        defined as no caloric intake for at least 8 hours.

    3) Two hour plasma glucose equal to or grater than 200 mg/dl (11. Immol/lit) during an

        oral glucose tolerance test

The test should be performed by using an oral glucose load equivalent of 75 gram

anhydrous glucose dissolved in water.

For epidemiological studies, estimates of diabetes prevalence and incidence should be based

on fasting plasma glucose equal to or greater than 126 mg/dl (7.0mmol/lit). Diabetic control

monitoring is based on glycated hemoglobin levels in the peripheral (antecubital vein)

blood. It is based on the fact that glucose binds to blood hemoglobin within the circulating

erythrocytes and remain attached for the life cycle of the blood cell. It measures the blood

glucose levels over a period of 8 to 12 weeks. Good metabolic control of diabetes is

glycated hemoglobin levels below 7.0 %. Fair metabolic control is glycated hemoglobin

between 7.1 to 8.2 %. Poor metabolic control is glycated hemoglobin level more than 8.3 %

was considered as criteria to classify metabolic control of diabetes mellitus.




                                                84
                                                                                  Appendix -1



Oral hygiene status:

Oral hygiene status was determined by the components of the oral hygiene index of Greene

and Vermillion: debris and calculus index (Greene & Vermillion, 1960). A total of six

segments including all teeth except third molars in the oral cavity were selected for

calculating oral hygiene status. The debris and calculus scores can be determined by totaling

the scores recorded and then dividing by the number of segments scored The simple

addition of two indexes is expressed as oral hygiene index.

Criteria for calculating the debris index:

    •   0 is No debris or stain present

    •   1 is Soft debris covering not more than one third of the tooth surface, or the presence

        of extrinsic stains without other debris regardless of surface area covered

    •   2 is Soft debris covering more than one third, but not more the two thirds, of the

        exposed tooth surface

    •   3 is Soft debris covering more than two thirds of the exposed tooth surface.

Criteria for calculating the calculus index:

    •   0 is No calculus present

    •   1 is Supra-gingival calculus covering not more than one third of the exposed tooth

        surface

    •   2 is Supra-gingival calculus covering more than one third but no more than two

        thirds of the exposed tooth surface or the presence of individual flecks of sub-

        gingival calculus around the cervical portion of the tooth or both.

    •   3 is Supra-gingival calculus covering more than two thirds of the exposed tooth

        surface or a continuous heavy band of sub-gingival calculus around the cervical

        portion of the tooth or both.



                                               85
                                                                                     Appendix -1


Gingivitis index:

The gingivitis index was recorded according to criteria used by Jackson (Jackson, 1965). To

each papilla or margin studied, a score will be given according to the severity of gingivitis.

The gingivitis index is calculated by addition of the total number of scores divided by total

number of surfaces calculated.

Criteria for calculating the Gingivitis index:

      •    0 is no inflammation

      •    1 is earliest detectable lesion

      •    2 is well established lesion with out swelling

      •    3 is lesions which could not be classified as either 2 or 4

      •    4 is severe lesions with considerably swollen tissues

Body mass index:
Obesity was determined by body mass index. The parameters used are the weight in

kilograms and height in meters squared. Dividing the weight in kilograms by height in

meters squares derives the body mass index.

The       interpretation   of the     results   is by WHO expert         technical   consultation

recommendations (WHO Expert Consultation, 2004). In Asia those with BMI above 23 are

considered as over-weight and in excess of 25 as obese.

TNF-alpha:

TNF-alpha is a pro-inflammatory cytokine which interferes with insulin action, probably by

inhibiting tyrosine kinase activity of insulin receptor. Phosphorylation of the insulin

receptor by this tyrosine kinase is known to be a cardinal step in the post receptor events

that follow the binding of insulin to its receptor. The normal level of serum TNF-alpha is

0.72 ±0.28 pg/ml (Dandona et al, 1998) and the elevated levels could be found in diabetes,

periodontal disease, obesity etc (Dandona et al., 1998; Delima et al., 2001).


                                                  86
                                                                               Appendix -1



TNF-alpha levels were measured by drawing blood from antecubital veins and the blood

was allowed to clot and serum was extracted. Serum samples were assayed for TNF-alpha.

Serum TNF-alpha levels were measured with a commercially available Quantikine® TNF-

alpha high sensitivity immunoassay kit. This enzyme linked immunosorbent assay kit

(Quantikine® HS) has a sensitivity of 0.3 pg/ml, this allows the measurement of TNF-alpha

in the normal range in human plasma/serum. The coefficient of variation for this kit is 7% at

high concentrations and 10% at lower concentrations.




                                              87
                                                                          Appendix - II



                                         Appendix - II

PPDHNo.                                                          2 0 0
HU-DBI (adult)

Name:                                        Sex         1=M 2 = F

Blood type:             O=l               A=2                            AB = 4      Unknown = 9

Occupation:             1.   Clerk           2. Profes                    3.   Retail and
                                                /technical personnel           Service industry
              4.  Executive                  5. Self-Employed             6.   Freelancer
              7.  Fishing, Agriculture,      8. Technician                9.   Housewife
                  Forestry
              10. Student                 11. Others, please specify
                  (Secondary      school-
                  higher forms: F4/5/6_
                  University: Year

Please mark YES or NO for your answer. Please tell us exactly what you feel and
do.

                                                                                          Yes No
                                                                                          = 1 =0
1.   I have not much resistance to visiting a dentist.
2.   My gum bleeds frequently on tooth brushing.
3.   I am concerned about the colour of my teeth.
4.   I have come across/seen white sticky and soft tooth deposits.
5.   I am using a small toothbrush designed for children (school children).
6.   I think that denture-wearing is unavoidable upon ageing.
7.   I am concerned about the colour of my gums.
8.   I think my teeth are getting worse despite my brushing.
9.   I pay attention to each tooth during my tooth brushing.
10. I have not been taught professionally, in particular, the method of tooth brushing.
11. I am sure I can keep my mouth clean even without using any toothpaste,
12. I often check my teeth in a mirror after brushing.
13. I am concerned about my bad breath,
14. I think tooth brushing alone cannot prevent periodontal disease.



                                            88
                                                                             Appendix - II



15. I put off going to the dentist for treatment until I have a toothache.
16. I have used dye to disclose the "dental plaque" on my teeth.
17. I am using a toothbrush with hard bristles.
18. I don't feel I've brushed well unless I brush with strong/heavy strokes.
19. I feel I sometimes spend too much time to brush my teeth.
20. My dentist has commended me on my tooth brushing method.




                                              89
                                                                         Appendix - II




PPDHNo.                                                     2 0 0          Y         M           D

JRHQ

Please circle the answer which fits best.

1. Do you chew your food well when you eat?
   (1) Yes                (2) Relative well            (3) Not so well          (4) No

2. Do you like to eat fatty meat?
   (1) Yes                   (2) Yes, rather           (3) Not so much           (4) Seldom

3. Do you always eat until you feel very full?
   (1) Eat very much        (2) Eat relatively         (3) Eat to some           (4) Eat less
                                much                       extent

4. Do you often drink carbonated drinks and juice?
   (1) Yes, often          (2) Relatively often        (3) Not often             (4) Seldom

 5. Do you like to eat cakes and sweets?
    (1) Yes, very much        (2) Relatively often     (3) Not often             (4) Seldom

 6. Do you eat a lot of vegetables?
    (1) Yes                  (2) Relatively a lot      (3) some                  (4) Seldom

 7. Do you take your meals at regular times?
    (1) Yes                 (2) More or less            (3) Somewhat             (4) Irregular
                                                            irregular

 8   How many times a week do you eat out for dinner?
     (1) More than 3       (2) Around 2               (3) Once                    (4) Rarely

 9. How often in a week do "three meals a day" turn into two meals a day for
    you?                                                                          (4) More than
    (1) Rarely              (2) About once a           (3) About twice a
                                week                       week                       three times a
                                                                                      week

  10. Did you eat many sweet snacks as a child?
                                                        (3) Not much              (4) Never
      (1) Often               (2) Somewhat often

  11 Do you move your body briskly?
    '(l)Yes                (2) Yes, I tend to            (3) No, not really

  12 Do you tend to do what is good for your health?
     (l)Yes                   (2) Yes, as far as         (3) Not much
                                  possible


                                               90
                                                                            Appendix - II




13. Do you take care not to gain weight?
    (1) Yes                  (2) I try                   (3) No, not really        (4) Not at all

14. Are you concerned about your lack of exercise?
    (1) Yes, very much     (2) Somewhat worried          (3) Not too worried       (4) No, not at all

15. If you have decided to exercise, do you continue to do so for a long time?
    (1) Yes                  (2) Yes, usually            (3) No, usually not       (4) No

16. Do you spend your days off watching TV?
    (1) Yes, most of the   (2) Often                     (3) Not so often          (4) Rarely
        time

17. Do you ever fall asleep against your will?
    (1) Very often           (2) Often                   (3) Not often             (4) Rarely

18. How much do you get sleep a day?
    (1) More than 7.5      (2) Around 7 hours            (3) Around 6 hours        (4) Less than 5.5
        hours                                                                          hours

19. Do you sleep well?
    (1) Yes                   (2) OK                     (3) Some difficulty

20. Are you confident in maintaining your own health?
    (1) Very much           (2) Yes                   (3) Not much                 (4) No

21. Are you satisfied with your work?
    (1) Yes, very much       (2) Yes                     (3) No, not really

22. Do you feel stressed?
    (1) yes, often            (2) yes, sometimes         (3) to some extent

23. Do you feel that you get tired easily?
    (1) Yes, very often       (2) Often                  (3) Sometimes

24. Do you drink medicated energy drinks to restore your tiredness?
    (1) Yes, often         (2) Relatively often        (3) Not often

25. Do you drink too much alcohol?
    (1) Yes, often         (2) Relatively often          (3) Not often

26. Do you follow the instruction of the doctor/nurses, even when it is a bit
    Troublesome?
    (1) Yes                  (2) Relatively, yes         (3) To some extent        (4) Not really

27. What is your present :Height                                   Weight



                                             91
                                                                      Appendix - II



28. Have your ever had any of the following diseases?
    (You may pick more than one response.)
    (1) High blood          (2) Stroke                (3) Heart disease      (4) Diabetes
        pressure                                                             (Please continue
                                                                             with next session)
                             Thank you for your cooperation




                                           92
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