Diabetic complication

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					      Diabetic complication

          Acute complication
 Hypoglycemic coma
 Diabetic ketoacidosis
 Nonketotic hyperosmolar coma
       Diabetic late complication
   A. Macrovascular compliction
      1. IHD
      2. CVD
   B. Microvascular compliction
       1. Diabetic retinopathy
       2. Diabetic nephropathy
       3. Diabetic neuropathy
       4. Diabetic foot
       5. dermopathy
      Diabetic late complications
   Learning objectives
    1. Understand why good diabetic control reduces the
      incidence of long-term complications.
    2. Differentiate between micro- and macrovascular
      damage, and the diseases they cause.
    3. Understand the other complications that are
      associated with diabetes.
    4. Know the main findings of the DCCT & UKPDS
      studies for type 1 and type 2
    5. Identify some of mechanism by which glucose
      can cause long-term complication of diabetes
       Diabetic late complications
   Diabetes and its associated hyperglycaemia
    are medically significant for two main
   First, in the early stages they lead to illness
    that at best reduces the quality of life and at
    worst is fatal (e.g. ketoacidosis).
   Secondly, hyperglycaemia over many years
    leads to damage to several tissues in the
    body, producing so-called diabetic
       Diabetic late complications
   Effective treatment of diabetes is, therefore,
    not only important for improving the well-
    being of people with the disease in the short-
    term, but also for prolonging their lives and
    reducing morbidity and mortality from long-
    term complications.
   The single most important research finding in
    recent years is the confirmation that keeping
    plasma glucose concentrations close to
    normal reduces the incidence of long-term
     Glucose Control Study Summary
The intensive glucose control policy maintained a
lower HbA1c by mean 0.9 % over reduction in risk of:
  12%    for any diabetes related endpoint p=0.029
  25%    for microvascular endpoints       p=0.0099
  16%    for myocardial infarction        p=0.052
  24%    for cataract extraction          p=0.046
  21%    for retinopathy                  p=0.015
  33%    for nephropathy                 p=0.000054
        Diabetic ketoacidosis

 The most frequent endocrine emergency
  seen by the primary care physician
 May be the 1st presentation of type 1 DM
 Result from absolute insulin deficiency or
  increase requirement
 Mortality rate around 5%
    Precipitating causes for DKA
 Infection
 Trauma
 MI
 Stroke
 Surgery
 Emotional stress
 Inadequate intake or poor compliance
 Increase secretion of counter regulatory h
        Clinical presentation
 Polyurea and polydipsia
 Nausea and vomiting
 Anorexia and abdominal pain
 Kussmaul breathing
 Tachycardia
 Fruity odor of the breath
 Hypotonia,stupor and coma
 Sign of dehydration
         Diagnosis of DKA
 Hyperglycemia
 Ketonuria and ketonemia
 Acidosis (PH< 7.3 or bica < 15 mmol/l)
         Laboratory finding
 Serum glucose
 Keton
 Serum electrolyte
 Blood urea
 Serum amylase
 Septic work-up
         Treatment of DKA

 Fluid replacement
 Electrolyte correction
 Acidosis correction
 Insulin therapy for hyperglycemia
 Treatment of ppt cause
         Complication of DKA
   Metabolic abnormality
    a. sever acidosis
    b. hypokalemia and hyperkalemia
    c. Hypoglycemia
   Cerebral edema
   Vascular thrombosis
   Infection
   MI
   Acute gastric dilatation
   Respiratory distress syndrom
        Hypoglycemic coma
 Hypoglycemia is the most frequent acute
  complications in type 1 diabetes
 There are no consistent or agreed definition
  of hypoglycemia
 In theory the hypoglycemia is the level of
  blood glucose at which physiological
  neurological dysfunction begins
       Clinical manifestation of
           hypoglycemia 1
   Autonomic activation
    1. Hunger
    2. Tremor
    3. Palpitation
    4. Anxiety
    5. Pallor
    6. Sweating
        Clinical manifestation 2
   Neuroglycopenia
     1. Impaired thinking
     2. Change of mood
     3. Irritability
     4. Headache
     5. Convulsion
     6. Coma
        Predisposing factors
 Missed meal
 Change in physical activity
 Alterations or errors in insulin dosage
 Defective in counter regulatory hormones
 Alcohol ingestion
    Treatment of hypoglycemia

 In mild cases oral rapidly absorbed
 In sever cases (comatose patient) iv hyper
  tonic glucose 50% or 25% concentration
 Glucagons injection
           Diabetic retinopathy
   It is the leading cause of blindness in adult
   Approximately 5% of patients with diabetes
    progress to sever visual acuity loss
   In type 1 DM after 15 y the risk of having DR
    98%.1/3 macular edema 1/3 PDR
   In type 2 diabetes after 15 y 78% DR
   10-18% of NPRDR progress to PDR
   ½ of the patient with PDR progress to blindness
    in 5y time
         Classification of DR 1
   Non proliferative DR
    1. Increased capillary permeability
    2. micro aneurysms
    3. Retinal hemorrhage (dot & blots)
    4. Hard exudates
    5. Venous beading
    6. Diabetic macular edema
         Classification of DR 2
   Proliferative diabetic retinopathy
     1. New vessels
     2. Vitreous hemorrhage
     3. Retinal detachment
     4. New viscualization of the iris
          (Rubeosis iridis)
     5. Scar (retinitis proliferanse)
     Diabetic late complications

 Fluorescein
  angiogram. This
  shows abnormalities
  in the capillaries of
  the retina in the
Normal Retina
Diabetic Retinopathy

            Cotton wool spots
Proliferative Retinitis:
             Retinal detachment
             Laser cauterization
       Diabetic late complications
   Background
    showing red
    ‘dots and blots’
    aneurysms and
    and exudates.
       Diabetic late complications

    Proliferative
    retinopathy. Note
    the abnormal
    capillaries and
       Diabetic late complications
    Maculopathy in an
    NIDDM patient.
   Note the
    characteristic ring
    of leaked material
    (exudates) around
    the macula region.
       Diabetic late complications
   All forms of
    increase in
    frequency in
    diabetic patients as
    the duration of
    diabetes increases.
              Treatment of DR
   Glycemic control
   Control of blood pressure
   Control of blood lipid
   Drug therapy
    1. Aldose reductase inhibitor
    2. Pentoxifylline
    3. Platelets inhibitors
   Laser therapy
   Vitrectomy surgery
       Kidney Disease in Diabetes Patients

–   27,851 new cases of ESRD in diabetes patients in 1995
    » 40% of all new cases in the US
–   Nearly 99,000 diabetes patients required dialysis or kidney
    transplantation that year
–   Annual cost of ESRD:
    » $45,000 in diabetic patients ages 45-64
    »35% of type 1 develop this complication

                                             National Diabetes Fact Sheet. November 1, 1997:1-8.
                                       U.S. Renal Data System, USRDS 1997 Annual Data Report.
        Relationship Between Hyperglycemia
                  and Nephropathy

–   Diabetic nephropathy: persistent proteinuria
    (total excretion >500 mg/day), resulting in ESRD
    » 25% to 50% of diabetes cases
    » mortality from all causes in ESRD patients
      20X to 40X higher than in those without renal dysfunction
–   Preceded by microalbuminuria (protein excretion
    30–300 mg/day)
    » 20X higher risk of nephropathy than in normoalbuminuric
           O’Meara YM et al. In: Harrison’s Principles of Internal Medicine. 14th ed. 1998:1545-1553.
                                         Trevisan R, Viberti GC. In: Diabetes Mellitus. 1996:727-737.
    Pathological pattern of DN
 Diffuse form (more common) consist of
  widening GBM with generalized mesangial
 The nodular form (accumulation of periodic
  acid schiff positive material are deposit in
  the periphery of glomerular tufts (the
  Kimmelstiel-Wilson lesion)
           Staging of DN 1
 Stage 1
  a. increase in the GFR
  b. hyper functioning and hypertrophy
 Stage 2 occurs 2-3 y of the onset of DM
  characterized histologically by
  a. glomerular mesingial expansion
  b. glomerularsclerosis
  c. basement membrane thickenings
  c. without clinically apparent disease
               Staging of DM 2
   Stage 3 occurs 7-15 y after the onset of DM
    a. stage of incipient nephropathy
    b. increase in urinary albumin in the rang of
    c. it is the earliest lab evidence of DN
   Stage 4 is overt nephropathy characterized
    a. protienuria
    b. normal or decrease GFR
    c. intervention can slow but not reserve the
    progression to RF
    d. the decline in renal function can be expected to
    occur in rate appro I mml/per month
              Staging of DN 3
   Stag 5 occur in 20-40 y after the onset
    a. associate with a continuing decline in
    b. Increase in blood pressure
    c. between 50-75% progress to ESRD
    within 10-15 y
            Risk factors of DN
   Hyperglycemia
   Hypertension
   Microalbuminuria
   Duration of DM
   F.H OF hypertension,CVD,nephropathy
   Ethnicity
   Male gender
   Cigarette smoking
   Gene
Treatment to prevent progression
             to DN
 Glycemic control
 ACE inhibitor (microalbuminuria)
 Blood pressur control
 Smoking cessation
 Proteins restriction
 Lipid reduction
                           diabetic Neuropathy
– Slowly progressive disease preferentially affecting the
  long axons
– 30% to 40% of all diabetics are symptomatic
    » 60% have neuropathy (symptomatic or asymptomatic)
–   Peripheral symptoms:
    » numbness/tingling in the feet, cramps, sensitivity/
      insensitivity to touch, loss of balance/coordination
–   Autonomic symptoms:
    » urinary incontinence, loss of sexual response, gastric
      stasis, orthostatic hypotension
–   Exact etiology unknown
              Diabetic Neuropathy. July 1995 (updated 1996). NIDDK publication NIH 93-3185.
                                            Vinik AI et al. In: Diabetes Mellitus. 1996:737-751.
         Classification of DN
 Peripheral neuropathy
  a. distal symmetrical sensory loss
  b. motor neuropathy
  foot drop,wrist drop
  diabetic amyotrophy
 Cranial neuropathy
  cranial nerves affected 111,1V,V1,V11
          Classification of DN
   Autonomic neuropathy
    a. postural hypotension
    b. resting tachycardia
    c. loss of sweating
    d. gastrointestinal neuropathy
    gastroparesis,diabetic diarrhea
    e. urinary bladder atony
    f. erectile dysfunction
           Treatment of DN
 Simple analgesia
 Tricyclics antidepressants
 Anticonvulsants
 Other measure
  a. mexilitine
  b. gamma linolenic acid
  d. capsaicin
    Foot Ulcers and Amputations in Diabetes

–   >50% of lower limb amputations in the US
    » 67,000/yr (1993 -1995)
– Foot ulcers occur in 15% of diabetes patients over
a lifetime
– Cost of diabetes-related amputation: $27,000

                                National Diabetes Fact Sheet. November 1, 1997:1-8.
                       Reiber GE et al. In: Diabetes in America. 2nd ed. 1995:409-428.
       Risk of foot ulceration
 Male sex
 Increasing age
 Peripheral vascular disease
 Neuropathy
 Low socioeconomic status
 Limited joint mobility
 Poor education of patient
Treatment of diabetic foot ulcers
 Infection
  a. Surgical drainage
  b. appropriate antibiotic
 Vascular component
  a. consider revascularization
 Neuropathic ulcers
  a. protect foot from stress
                     Foot ulcer
   A foot ulcer in a
    diabetic patient, most
    probably due to nerve
    damage. Note the
    callus (hard skin)
    around the ulcer,
    indicating that the foot
    was subjected to
    excess pressure.
Diabetic Gangrene
Diabetic Gangrene – Amp.
              Heart Disease and Stroke in
                   Diabetes Patients

–   Evidence of CHD in 7.5%-20% of diabetes patients
    >45 years old in the US
    – 55% of deaths in diabetes patients are caused by
      cardiovascular disease
–   5-year average cost of surviving acute MI: >$51,000
–   Stroke occurs 2X- 4X more often in diabetes patients

                     Diabetes complications. In: Diabetes 1996 Vital Statistics. 1996:29-44.
                                    National Diabetes Fact Sheet. November 1, 1997:1-8.
                                          Wittels EH et al. Am J Cardiol. 1990;65:432-440.
Relationship Between Glycemic Control
and Coronary Heart Disease Events in
Type 2 Diabetes Patients (Ages 65 to 74)

3.5-yr Incidence (%)

                                                                                  HbA1c <7.0%
                                                                                  HbA1c 7.0%



                            <6                        6
                                 Duration of Diabetes (yr)

                                                       Kuusisto J et al. Diabetes. 1994;43:960-967.