Diabetes mellitus (DM):
DM is considered as global problem. There will be about 400 million persons will suffer
from DM in year 2025 so DM is considered as a major health problem. In Jordan, the
incidence of the disease is increasing and about 15% of population above the age 25 years.
The highest of DM is found in the Middle East area, this was due to changes in life style,
food habits and decrease of exercise. The highest incidence in Arab countries was
observed in Bahrain followed by Saudi Arabia, and Jordan. The incidence is higher in
developing countries than developed countries, due rapid changes in life style. In
developing countries the incidence of the disease is increasing by about 1.6% every year.
About 6% of American population is suffering from DM which represents about 20
In past DM was considered as disease of old age, where about 20% of ages above 65 years
suffering from DM. Due to rapid increase in the incidence of obesity, this will causes first:
the age incidence is now decreasing and younger persons will be suffering of DM, second
expanding of the disease where more and more peoples are affected with this disease.
Example: if we have 2000 persons about 40 to 85 persons have DM.
It is a metabolic disorder characterized by absolute deficiency of insulin in type I DM and
relative insulin deficiency or insulin resistance in type II DM. The major function of
insulin is to control blood sugar also to control other metabolic needs as lipids and protein.
Our pancreas secretes about 50 unite of insulin every day in order to keep blood sugar in
normal rages are: FBS (fasting blood sugar) 80-100 mg/dL and post-prandial (after 2 hour
meal) not more than 140mg/dL. In normal persons the pancreas will secrete enough insulin
to keep blood sugar in normal rages, but when we have insulin deficiency or insulin
resistance; the level of sugar will exceeds the normal ranges (hyperglycemia) and the
person will develop DM.
Types of diabetes mellitus:
A. Primary DM:
1. Type I DM:
New name: type I diabetes mellitus.
Insulin dependent diabetes mellitus: (because the major line of treatment is insulin); or
Juvenile Diabetes mellitus: (because it affects mainly young peoples).
Juvenile diabetes mellitus: because it affects young ages.
Ketosis-prone diabetes mellitus: because the patient are more susceptible to develops keto-
It is causes by auto-immune destruction of β cell of islets of Langerhans by 90%. Beta cell
is responsible for secretion of insulin. Because it is an auto-immune disease, there is an
increase in Glutamic Acid Decarboxylase (GAD) Antibodies, insulin antibodies, anti-beta
It represents about 5 to 10% of all cases of primary DM. It is less common than type II
DM, which represents about 90 to 95% of all cases of primary DM.
It mostly affects young age groups with peak age is around 15 years.
Peak occurrence time is in winter this why it have suggested that viral infection may play a
role in this disease.
1. Absolute deficiency of insulin.
2. High incidence of complication, this is because the patients are young and they have
longer duration of the disease which may extend to 20 or even 25 years which gives a
higher chance of developing complication of DM (Late onset complication).
Because type I DM is an autoimmune disease this is why it can associated with other
autoimmune diseases such as Hashimoto's and graves disease of the thyroid, Adrenal
gland insufficiency, Addison disease Systemic lupus erytheromatosis (SLE) and
Rheumatoid arthritis which are group of autoimmune disease and are sorted together.
1. Genetic factor:
Numerous susceptibility loci (genes that predispose to type I DM) have been found.
Several of these loci are located in major histo-compatibility complex (MHC) region on
the short arm of chromosome 6 which contains genes that regulate the immune response.
The incidence is greatly increased in individuals with a specific point mutation in HLA-
DQ gene (HLA: human leukocyte antigen). For example, the presence of HLA-DR3 and
HLA-DR4 are associates with high risk of developing DM.
2. Viral infection:
Epidemics of viral infections in the winter months are associated with increase in the
incidence of DM. Several viruses (e.g. coxsakie B, entro-viruses, rubella, mump, and cyto-
megalo-virus) have been implicated in the etiology of type I DM. Possible mechanism for
their effect include molecular mimicry المحاكااin which the immune response to infection
cross-reacts with islet antigens. Alternatively, viral infection, including those occur
antenatally, may have more direct effect on β cell.
3. Environmental factors:
Brest feeding seems to provide protection against the risk of developing type I DM. Many
mew patients with type I DM have IgG antibodies to bovine serum albumin (protein in
cow milk) with similarities to islet cell antigen. This protein stimulates auto-antibodies
production leading to islet cell destruction as a result of molecular mimicry .المحاكا
b. Chemical toxins:
Ingestion of the rodenticids (example vacor) is associated with development of type I DM.
Prior to the onset of type I DM have, adult have been shown to experience more "sever life
events" than control group. The cause of this is unclear but may relate to stress-induced
impairment of resistance to infection in genetically susceptible individuals.
The cause may be a genetic predisposing complicated by autoimmune inflammation of
islet (insulitis) triggered by viral infection or environmental factor. Islets are small and
beta cells are greatly decreased or absents.
Insulitis is an inflammation of the islets of Langerhans of the pancreas. Pancreatic β-cells
become infiltrated by mononuclear cells (lymphocytes); leading to inflammation. This
lymphocyte infiltration can result in destruction of the insulin producing beta cells of the
islets. This will causes sever deficiency of insulin production that will end with DM.
The process of destruction may take long time but when 90% of beta cells destructed the
patient start to develop sever symptoms.
Unless insulin is replaced, type I DM result in marked carbohydrate intolerance with
hyperglycemia, leading to polyuria ,كثر التبولpolydipsia , كثر شرب المااweight loss despite
increase appetite, ketoacidosis.
About 50% of patients with type II DM are a-symptomatic (without symptoms).
2. Type II DM:
New name: type II diabetes mellitus.
Non-Insulin dependent diabetes mellitus: (because the major line of treatment is dietary
control or oral hypoglycemic drugs);
Adult-onset Diabetes mellitus: (because it affects mainly old age peoples).
Ketosis-resistance diabetes mellitus: because the patients are less likely to develops keto-
Type II disease is due to increase insulin resistance mediated by: decrease cell
membrane insulin receptors post-receptor dysfunction impaired processing of pro-
insulin to insulin decrease sensation of glucose by beat cells impaired function of
intra-cellular carrier protein. Plasma insulin concentration is normal and often increased.
Ketoacidosis is unusual but dose occurs, characteristically precipitated by unusual stress
such as infection or surgery.
Type II DM characteristically begins later in life, most often in middle age. The incidence
of the disease increases with increasing in age. About 20% of people after the age of 65
may have type II DM all over the world.
Type II DM is most often associated with over weight of obese.
Obesity involves having an abnormally high proportion of body fat.
Body mass index= weight (kg) / [(height (m)2]
Underweight: from 16.5 to 18.5k, Normal: from 18.5 to 25, Overweight: from 25 to 30,
Obese: more than 30.
Focal islet fibrosis and hyalinization (due to deposit of amylin) are characteristics but not
specific. Amylin (also known as islet amyloid polypeptides: IAPP) deposition in
pancreatic islets is characteristic of typeII DM and is thought to interfere either with
conversion of pro-insulin to insulin or with the sensing of insulin by beta cells.
Type II DM is a complex metabolic disorder of heterogeneous etiology with social,
behavioral and environmental risk factors unmasking the effects of genetic susceptibility.
Although environmental factors are usually required for the development of type II DM,
genetic influence is clearly supported by three types of data: twin studies, familial
aggregation of the disease evidenced by a very high positive rate of family history of
diabetes, and drastically difference prevalence in various ethnic groups.
What are the main risk factors?
The number one risk factor for type 2 diabetes is obesity. Greater weight means a higher
risk of insulin resistance, because fat interferes with the body's ability to use insulin. The
adverse effect of obesity on glucose metabolism is evident early in childhood. Obese
children are hyper-insulin-aemic and have approximately 40% lower insulin-stimulated
glucose metabolism compared with non-obese children. Furthermore, the inverse
relationship between insulin and abdominal fat is strong for visceral than for subcutanous
fat. It is interesting to note that adipose tissue expanding in obese state synthesize and
secret metabolites and signaling proteins such as adiponectin, tumor necrotic factor-alpha,
leptin and resistin. These factors are known to alter insulin secretion and sensitivity and
even cause insulin resistance.
2. Sedentary Lifestyle (exercising less than 3 times a week)
3. Unhealthy Eating Habits
4. Family History and Genetics
5. Increased Age
6. High Blood Pressure (greater than or equal to 140/90 mmHg)
7. High Cholesterol
HDL cholesterol under 35 mg/dL and High blood levels of triglycerides (250 mg/dL or
8. Diabetes during a previous pregnancy and given birth to a baby weighing more than 9
At early stage of the disease the pancreas try to compensate by hyper-insulin-emia to over
come hyperglycemia; but with time beta cell will be tired and destroyed. Long term
presence of DM there will be destruction of beta cells and at this stage it will resemble that
of type I.
What are the main differences between DM type I and II?
Type I: Any age mostly in young age group (before 20), when it occurs in old age called
(late onset DM).
Type II: mostly in old age group (after 30), but due to obesity we begin now to see it in
Type I: deficiency of insulin.
Type II: normal or high due to insulin resistance with poor quality of insulin.
3. Increase Keton-bodies:
Type I: common
Type II: rare.
Type I: found where there is an increase in Glutamic Acid Decarboxylase (GAD)
Antibodies, insulin antibodies, anti-beta cell antibodies
Type II: no auto-antibodies.
Type II DM Has positive family history more frequent than Type I DM
6. Body weight:
Type I: Normal weight.
Type II: obese.
Type I: common
Type II: rare.
Type I: auto-immune antibody causes sever inflammatory reaction of beta cells that will
end with fibrosis, and sever beta cell depletion.
Type II: there is mild depletion of beta cell, and may take 10 to 15 years to have sever
depletion of beta cells; this why 40% of DM type II may need insulin as treatment.
Secondary Diabetes mellitus
1. Diseases related to pancreas: Chronic pancreatitis, Pancreatectomy, Pancreatic
neoplasia, Cystic fibrosis, Hemochromatosis.
2. Endocrinal disorders: Growth hormone excess (acromegaly), Cushing syndrome,
3. Drugs: Glucocorticoids, Thyroid hormone.
Gestational diabetes mellitus:
It is development of during pregnancy, even if she is diabetic patient and discovered
About 5 to 10 % of women may suffer of gestational DM. About 90% of suffering of
gestational DM clears up of hyperglycemia (i.e. return to normal FBS (fasting blood
sugar) and GTT (glucose tolerance test) after 6 weeks of delivery, unless they do have
diabetes mellitus before pregnancy. Thos women with gestational DM are more
susceptible to develops gestational DM in second pregnancy. About 50% of women with
gestational DM will develop type II DM after 10 years. This is why they have to continue
monitors their blood sugar every 6 month or at least every year.
Maturity onset diabetes of the young (MODY)
It is caused by mutations in an autosomal dominant gene. MODY is often referred to as
"monogenic diabetes" to distinguish it from the more common types of diabetes
(especially type 1 and type 2), which involve more complex combinations of causes
involving multiple genes (i.e., "polygenic") and environmental factors. MODY
characterizes by: mild hyperglycemia (acts like a very mild version of type 1 diabetes),
hypo-secretion of insulin production normal insulin sensitivity but no loss of beta
cell. MODY is not type II diabetes in a young person, as might erroneously be inferred
from the name; it has an earlier onset than type II DM.
Humans are capable of digesting some carbohydrates, in particular those most common in
food; starch, and some disaccharides such as sucrose, are converted within a few hours to
simpler forms most notably the monosaccharide glucose, the principal carbohydrate
energy source used by the body. The rest are passed on for processing by gut flora largely
in the colon. Insulin is released into the blood by beta cells (β-cells), found in the Islets of
Langerhans in the pancreas, in response to rising levels of blood glucose, typically after
Insulin is used by about two-thirds of the body's cells to absorb glucose from the
blood for use as fuel, for conversion to other needed molecules, or for storage.
Insulin is the principal hormone that regulates uptake of glucose from the blood into
most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore
deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of
Insulin is also the principal control signal for conversion of glucose to glycogen for
internal storage in liver and muscle cells.
Higher insulin levels increase some anabolic ("building up") processes such as cell
growth and duplication, protein synthesis, and fat storage. Insulin (or its lack) is the
principal signal in converting many of the bidirectional processes of metabolism from a
catabolic to an anabolic direction, and vice versa. In particular, a low insulin level is the
trigger for entering or leaving ketosis (the fat burning metabolic phase).
Symptoms may develop rapidly (weeks or months) in type I DM while in type II
diabetes they usually develop much more slowly and may be subtle or absent.
The classical symptoms of diabetes are:
Poly-uria (frequent urination), polydipsia (increased thirst):
When the glucose concentration in the blood is raised beyond its renal threshold (about
10 mmol/L, although this may be altered in certain conditions, such as pregnancy),
reabsorption of glucose in the proximal renal tubule is incomplete, and part of the glucose
remains in the urine (glycosuria). This increases the osmotic pressure of the urine and
inhibits re-absorption of water by the kidney, resulting in increased urine production
(polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from
water held in body cells and other body compartments, causing dehydration and increased
thirst (polydipsia ).
Polyuria will causes loss a lot amount of water and electrolytes (Na, K, Cl , Phosphate,
Mg) and decrease the amount of these electrolytes in blood.
We have to differentiate between polyuria and increase frequency of urination:
Increase frequency of urination: increase number of urination but with normal amount of
urine each time.
Polyuria: increase number of urination with increase amount of urine each time.
polyphagia (increased hunger) and loss of weight:
Patient with DM will feel of huger so they eat a lot food but still they loss weight probable
because insulin is anabolic hormone.
Any patient how eat excess amount of food but still loss weight this could be either DM or
People (usually with type 1 diabetes) may also present with diabetic keto-acidosis, a
state of metabolic dys-regulation characterized by the smell of acetone; a rapid, deep
breathing known as Kussmaul breathing; nausea; vomiting and abdominal pain; and an
altered states of consciousness.
The absence of insulin leads to the release of free fatty acids from adipose tissue, which
are converted, again in the liver, into ketone bodies (acetoacetate and β-hydroxybutyrate).
β-Hydroxybutyrate can serve as an energy source in absence of insulin-mediated glucose
delivery, and is a protective mechanism in case of starvation. The ketone bodies, however,
have a low pH and therefore turn the blood acidic (metabolic acidosis). The body initially
buffers the change with the bicarbonate buffering system, but this system is quickly
overwhelmed and other mechanisms must work to compensate for the acidosis. One such
mechanism is hyperventilation to lower the blood carbon dioxide levels (a form of
compensatory respiratory alkalosis). This hyperventilation, in its extreme form, may be
observed as Kussmaul respiration. The level of consciousness is typically normal until late
in the process, when lethargy may progress to coma. Ketoacidosis can easily become
severe enough to cause hypotension, shock, and death.
Diabetic ketoacidosis may be diagnosed when the combination of hyperglycemia (high
blood sugars), ketones in the blood or on urinalysis and acidosis are demonstrated.
Prompt, proper treatment usually results in full recovery, though death can result from
inadequate or delayed treatment, or from complications (e.g., brain edema). DKA is
always a medical emergency and requires medical attention. Ketoacidosis is much more
common in type 1 diabetes than type 2.
About 20% of patients with type I DM may presented with Diabetic keto-acidosis: DKA.
Treatment will be: IV fluid, insulin, correction of electrolytes, correction of
Complications of DM:
The complications of diabetes mellitus are far less common and less severe in people who
have well-controlled blood sugar levels. Wider health problems accelerate the deleterious
effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood
pressure, and lack of regular exercise.
A. Acute complications (treatable complication) :
1. Diabetic keto-acidosis
2. Hyper-osmolar non-ketotic state (HNS):
It is an acute complication sharing many symptoms with DKA, but an entirely different
origin and different treatment. A person with very high (usually considered to be above
300 mg/dl (16 mmol/L)) blood glucose levels, water is osmotically drawn out of cells into
the blood and the kidneys eventually begin to dump glucose into the urine. This results in
loss of water and an increase in blood osmolarity. Lethargy may ultimately progress to a
coma, though this is more common in type 2 diabetes than type 1.
Hypoglycemia, or abnormally low blood glucose, is an acute complication of several
diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients.
In patients with diabetes, this may be caused by several factors, such as too much or
incorrectly timed insulin, too much or incorrectly timed exercise (exercise decreases
insulin requirements) or not enough food (specifically glucose containing carbohydrates).
It begins in two stages: The symptoms of hypoglycemia begin with feeling of hunger,
sweating, palpitation, hypothermia due to increase sympathetic activity. Followed by CNS
symptoms (due CNS hypoglycemia (if blood sugar less than 40 mg/dL) which is called
neuroglycemia. Consciousness can be altered or even lost in extreme cases, leading to
coma, seizures, or even brain damage and death.
In most cases when the patient conscious i.e. in early stage hypoglycemia is treated with
sugary drinks or food. In severe cases i.e. late stage , an injection of glucagon (a hormone
with effects largely opposite to those of insulin) or an intravenous infusion of dextrose
(50% dextrose 20 to 30 mL/ IV) is used for treatment, but usually only if the person is
unconscious; try to avoid oral treatment in unconscious patient to avoid aspiration
pneumonia. In any given incident, glucagon will only work once as it uses stored liver
glycogen as a glucose source; in the absence of such stores, glucagon is largely ineffective.
In hospitals, intravenous dextrose is often used.
4. Diabetic coma
Diabetic coma is a medical emergency in which a person with diabetes mellitus is
comatose (un-conscious) because of one of the acute complications of diabetes:
a. Severe diabetic hypoglycemia
b. Diabetic keto-acidosis advanced enough to result in unconsciousness from a
combination of severe hyperglycemia, dehydration and shock, and exhaustion
c. Hyper-osmolar non-ketotic coma in which extreme hyperglycemia and dehydration
alone are sufficient to cause unconsciousness.
B. Chronic complications:
Chronic elevation of blood glucose level leads to damage of blood vessels (angiopathy).
The endothelial cells lining the blood vessels take in more glucose than normal, since they
do not depend on insulin. They then form more surface glyco-proteins than normal, and
cause the basement membrane to grow thicker and weaker. In diabetes, the resulting
problems are grouped under "micro-vascular disease" or micro-angio-pathy (due to
damage to small blood vessels) and "macro-vascular disease" or macro-angio-pathy (due
to damage to the arteries).
The damage to small blood vessels leads to a micro-angio-pathy, which can cause one or
more of the following:
1. Diabetic cardiomyopathy (heart), damage to the heart, leading to diastolic dysfunction
and eventually heart failure.
2. Diabetic nephropathy (kidney): damage to the kidney which can lead to nephrotic
syndrome, end stage renal disease and chronic renal failure, eventually requiring dialysis.
Diabetes mellitus is the most common cause of adult kidney failure worldwide in the
developed world, and about 50% of patient who needs dialysis is causes By DM, and
about 50% of patient with end stage renal disease is due to DM.
3. Diabetic neuropathy (nervous system): abnormal and decreased sensation, usually in a
'glove and stocking' distribution starting with the feet but potentially in other nerves, later
often fingers and hands. Sometime there is painful sensation (like pin and needle sensation
or burning sensation)
If it is combined with damaged blood vessels this can lead to diabetic foot.
Other forms of diabetic neuropathy may present as mono-neuritis or autonomic
neuropathy ( there is alteration of diarrhea and constipation or diarrhea only postural
hypotension impotence: 50% of male DM patients may complain of impotence (erectile
About 70% of DM patients will develops diabetic neuro-pathy.
4. Diabetic retinopathy (eye), growth of friable and poor-quality new blood vessels in the
retina as well as macular edema (swelling of the macula), which can lead to severe vision
loss or blindness. Retinal damage (from micro-angio-pathy) makes it the most common
cause of blindness among non-elderly adults in the US.
Diabetic retinopathy may associate with bleeding in the retina, retinal detachment and may
end with loss of sightedness. The commenest cause of blindness after the age of 60 is due
Macrovascular disease leads to cardiovascular disease, to which accelerated
atherosclerosis is a contributor:
1. Coronary artery disease, leading to angina or myocardial infarction ("heart attack").
Diabetic patient is about has about 2-4 times more chance to develops ischemic heart
2. Diabetic myonecrosis ('muscle wasting')
3. Peripheral vascular disease, which contributes to intermittent claudication (exertion-
related leg and foot pain) as well as diabetic foot.
4. Stroke (mainly the ischemic type)
5. Diabetic foot, often due to a combination of sensory neuropathy (numbness or
insensitivity) and vascular damage, increases rates of skin ulcers (diabetic foot ulcers) and
infection and, in serious cases, necrosis and gangrene. It is why diabetics are prone to leg
and foot infections and why it takes longer for them to heal from leg and foot wounds. It is
the most common cause of non-traumatic adult amputation, usually of toes and or feet, in
the developed world.
6. Carotid artery stenosis does not occur more often in diabetes, and there appears to be a
lower prevalence of abdominal aortic aneurysm. However, diabetes does cause higher
morbidity, mortality and operative risks with these conditions.
7. Diabetic encephalopathy is the increased cognitive decline and risk of dementia
observed in diabetes. Various mechanisms are proposed, including alterations to the
vascular supply of the brain and the interaction of insulin with the brain itself.
8. Liver: fatty liver changes is seen,
9. Skin: xanthomas (collection of lipid-laden macrophages in the dermis).
In the developed world, diabetes is the most significant cause of adult blindness in the
non-elderly and the leading cause of non-traumatic amputation in adults (it is the second
cause of amputation after accidents), and diabetic nephropathy is the main illness requiring
renal dialysis in the United States.
Fasting blood Sugar Random blood sugar glucose tolerance test (GTT)
(FBS) After 2 hours
DM: > 126 mg/dL >200mg/dL >200mg/dL >6.5%
Normal: <100 mg/dL <140 mg/ dL > 140 mg/dL < 5.8%
Pre-diabetic: 101-125 mg/dL 141-199 mg/dL
It is also called It is also called
Impaired FBS Impaired FBS
People with fasting glucose levels from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) are
considered to have impaired fasting glucose. Patients with plasma glucose at or above
140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g
oral glucose load are considered to have impaired glucose tolerance. Of these two pre-
diabetic states, the latter in particular is a major risk factor for progression to full-blown
diabetes mellitus as well as cardiovascular disease.
For changing unites from mg/dl to mmol/L:
7.0 mmol/L = 126 mg/dL, 11.1 mmol/L = 200 mg/dL, 7.8 mmol/L=140 mg/dL
Pre-diabetic or impaired FBS are liable to develops DM later on. About 5% of these will
develop DM every year.
GTT: two hours after a 75 g oral glucose load as in a glucose tolerance test.
Glycated hemoglobin (or glycosylated hemoglobin or HbA1c) is a form of hemoglobin
which is measured primarily to identify the average plasma glucose concentration over
prolonged periods of time. It is formed in a non-enzymatic glycation pathway by
hemoglobin's exposure to plasma glucose. Normal levels of glucose produce a normal
amount of glycated hemoglobin. As the average amount of plasma glucose increases, the
fraction of glycated hemoglobin increases in a predictable way. This serves as a marker for
average blood glucose levels over the previous months prior to the measurement.
The 2010 American Diabetes Association Standards of Medical Care in Diabetes added
the HA1c ≥ 48 mmol/mol (≥6.5%) as another criterion for the diagnosis of diabetes.
) كان يستعمل اتاا ا يات لة العاامتة ااستال ا ا انتا ا ن اسعلت يات لة وهو مت ة ي ت متاHA1c ( مالحضة:ان
يسلى ااع اكلي
The aim of treatment is to keep blood glucose as close as possible to normal to decrease
possibility of mortality and morbidity.
Type I DM:
First line of treatment: change life style and eating habits in addition to exercise.
Second line of treatment: Use insulin which is the only treatment. Oral hypoglycemic
drugs are not used.
Insulin is life saving drug this why patient before 1921 (time begin to insulin) may die
because of complication.
Type II DM:
First line of treatment: change life style and eating habits, in addition to exercise decrease
weight in obese patient.
Second: Oral hypoglycemic drugs families are:
1. Biguanine hypoglycemic drugs including metformin.
Metformin causes: reduce hepatic glucose production and intestinal absorption of glucose.
It doses not alter insulin secretion.
It increases peripheral insulin sensitivity.
It rarely causes hypoglycemia or weight gain. This why so patients use to reduce
It is used when there are no contraindications such as renal or liver failure and IHD.
2. Sulfonylureas hypoglycemic drugs including tolbutamide, acetohexamide, tolazamide,
glipizide, glyburide, glimepiride.
Sulfonylurea causes an increase in amount of insulin secretion by beta cell in response to
glucose. This is why main Side effect is hypoglycemia.
Sulfonylureas increase sensitivity to insulin, perhaps by increasing the number of insulin
) اهذا ااسلب فان اال ضى يأخذ ا قل يجلة ااطمتا ن سللهتاshort onset of action ( أن ذه االجل سة اها
3. Alpha-glucosidase inhibitors: Acarbose and miglitol:
Acarbose and miglitol are oligosaccharides or oligosaccharide derivatives.
They act as competitive reversible inhibitors of pancreatic alpha amylase and intestinal
alpha glucosidase enzyme; it acts in the lumen of intestine.
Inhibition of alpha glucosidase prolongs digestion of carbohydrates and reduces peak
plasma glucose, so improve post brandial sugar.
They rarely cause hypoglycemia.
They are weak drugs with many GIT side effects including nausea and vomiting.
4. Thiazolidinediones including pioglitazone (actos) and rosiglitazone:
Thiazolidinediones act by increasing tissue sensitivity to insulin.
Thiazolidinediones predominantly affect liver (decrease glucose output and decrease
insulin levels), muscle (increase glucose uptake), and adipose tissue (increase glucose
uptake and decrease fatty acid release).
Thiazolidinediones do not cause hypoglycemia.
Rosiglitazone withdrawn from the market after concern about its make an elevated risk of
They are oral insulin secretagogues leading to increase insulin secretion by beta cells.
These drugs cause hypoglycemia.
Sulfonylureas and Meglitinides cause hypoglycemia.
Biguanine, Alpha-glucosidase inhibitors and Thiazolidinediones don’t cause
6. Incretin mimetics
Incretins includes glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide.
Glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide both stimulates secretion
of insulin from beta cell.
Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-
A. Glucagon-like peptide agonists:
Exenatide is the first GLP-1 agonist approved for the treatment of type 2 diabetes.
Exenatide is not an analogue of GLP, but rather a GLP agonist. Exenatide has only 53%
homology with GLP, which increases its resistance to degradation by DPP-4 and extends
its half-life. Typical reductions in Hemoglobin A1C values are 0.5-1.0%.
B. Dipeptidyl peptidase-4 (DPP-4) inhibitors:
They increase blood concentration of the incretin GLP-1 by inhibiting its degradation by
dipeptidyl peptidase-4. Examples are: vildagliptin sitagliptin saxagliptin .
DPP-4 inhibitors lowered hemoglobin A1C values by 0.74%, comparable to other anti-
How to begin treatment:
According to American Diabetic Association the target of hemoglobin A1C is less than
According to United Kingdom Prospective Study (UKPS) has shown that reduction of
hemoglobin A1C values by 1% will reduce DM complication by 21%, heart attacks by
14%, and micro-vascular complications by 37% specially kidney complication
First step of treatment:
Change life style: will help to decrease hemoglobin A1C by 1 to 2%.
Second step of treatment:
Begin with Metformin will help to decrease hemoglobin A1C by 1.5 %.
Third step of treatment:
Add Sulfonylurea or Thiazolidinediones or DPP-4 inhibitors or insulin. We can choose
any one depending on the patients.
The choose of treatment will depend on the level of hemoglobin A1C example if
hemoglobin A1C is near 7% we choose change life style and Metformin but if hemoglobin
A1C is high lets say 11% we may need other drugs.
Patient should have continue visiting clinic every 3 months for follow up where we may
need to add another drug or change drug depending on patient responses. Finally we may
need to add insulin. Sometimes patients do not response well to small doses of insulin so it
will be necessary to increase the dose and number of injection till we control glucose
1. Periodontal disease and Gingivitis:
This is mainly due: to microvascular complications that lead to decrease neutrophils
Chemotaxis which decrease immunity which ends with increase infection,
hyperglycemia may causes increase collagen break down which end as mobile teeth
2. Salivary gland:
Polyuria and dehydration will cause decrease salivary flow (Xerostomia) and dry mouth.
Dry mouth will cause increase possibility of mouth infection and carries.
The tongue will be tender and painful with burning sensation.
4. Increase risk of oral infection:
The most important type of infection is Candida infection and it is due to:
a. Ultra microphage metabolism that decrease it phagocyte ability.
b. Peripheral neuro-pathy.
c. Poor peripheral circulation.
d. Hyperglycemia is good media for bacterial growth.
e. Decrease in antibody production.
5. Delay heeling of wounds:
It is caused by:
The walls of the vessels become abnormally thick but weak, and therefore they bleed, leak
protein, and slow the flow of blood through the body.
b. Decrease protein production.
Both will end with dry socket.
b. Neuro-pathy of facial nerve.
c. Mouth ulcers.
d. Side effects of Sulfonylurea
Before begin dental treatment full medical history should be obtained including medical
history: Ischemic heart disease, hypertension, DM). Mediation history; especially anti-
clotting drugs like Warfarin (which increase chance of bleeding) and if he/she taking any
oral hypoglycemic drugs or insulin.
It is better blood pressure and blood sugar, if blood sugar is not controlled its better to
refer patent to hospital for good control of blood glucose.
DM patients have higher possibility of infection so they may need prophylactic antibiotic
or developing hypoglycemia this is why try your best to treat such patient early in the
morning to avoid hypoglycemic attack specially if they on insulin treatment.
Excuse me for any mistake
Special greeting to all my friends and they who they are