Complications of diabetes mellitus
Objectives
At the end of this PDF Notes, student will be able to
• List the complications associated with DM
• Describe the pathophysiology involved in the
development of diabetic complications
• Describe Oral Glucose Tolerance Test
Clinical features of Diabetes mellitus
Type I DM
• Low plasma insulin levels
• Poly uria
• Polyphagia
• Polydipsia
• Ketoacidosis
• Hypoglycemic episodes
Type II DM
• Polyuria
• Polydipsia
• Unexplained weakness
• Plasma insulin normal to high
• Hyperosmolar non-ketotic coma
Pathophysiological basis of common signs and
symptoms due to uncontrolled hyperglycaemia in diabetes mellitus
Complication of DM – Pathogenesis
• Consequence of hyperglycemia
• Effects all most all the tissue
• Complications can either be acute or chronic
• 2 possible mechanism involved in development of complications
– Non-enzymatic protein glycosylation
– Polyol pathway mechanism
Non-enzymatic protein glycosylation
• Free amino group binds reversible to glucose
• Non enzymatic mechanism
• E.g. Hb with glucose (glycated Hb)
• Accumulates on collagen
• Irreversible advanced glycosylation end products (AGE)
• AGEs bind to receptors
• Biological & chemical changes
Polyol pathway mechanism
• Intracellular accumulation of sorbitol & fructose
• Entry of water inside cell
• Cellular swelling & damage
• Deficiency of myo inositol
• Harmful to retina
Acute metabolic complications
Diabetic ketoacidosis
• Complication of type I DM
• Due to shortage of insulin along with glucagon excess
• Failure to take insulin
• Lipolysis of adipose tissue
• Free fatty acids formed taken up by liver
• Converted ultimately to ketone bodies
• Excreted in urine
Hype osmolar non-ketotic coma
• Complication of Type II DM
• Due to sustained hyperglycemic diuresis
• Loss of glucose in urine
• Difficult to substitute the fluids lost of diuresis
• High viscosity of blood
• Bleeding complications
• Results in death
Hypoglycemic episodes
• Complication of type I & II DM
• Results from excess administration of insulin or oral hypoglycemic drugs
• May lead to permanent brain damage
• Worsening of diabetic control
Late systemic complications
• Atherosclerosis
• Diabetic microangiopathy
• Diabetic nephropathy
• Diabetic neuropathy
• Diabetic retinopathy
• Infections
Oral Glucose Tolerance Test (OGTT)
• Oral GTT is performed principally for patients with borderline fasting plasma glucose value (i.e. between 100-140 mg/dl)
• High carbohydrate diet for at least 3 days prior to the test
• overnight fast on the day of the test
• fasting blood sugar sample is first drawn
• 75 gm of glucose dissolved in 300 ml of water is given
• Blood and urine specimen are collected at half-hourly intervals for at least 2 hours
• Normal cut off value for fasting blood glucose level -100 mg/dl.
• Fasting blood glucose value in range of 100- 125 mg/dl – impaired fasting glucose tolerance (IGT)
• Fasting value of plasma glucose higher than 126 mg/dl
• 2-hour value after 75 gm oral glucose
• Higher than 200 mg/dl – diabetics
Summary
• Persistent hyperglycemia is associated with diabetic complications
• Non-enzymatic glycation and polyol pathway mechanism are the two main mechanisms involved in the development of complications of DM
• Acute metabolic complication and late systemic complication are major complications of DM
• Oral GTT is performed principally for patients with borderline fasting plasma glucose value (i.e. between 100-140 mg/dl)
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