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DIABETIS MELLITUS

INTRODUCTION: Diabetes mellitus is a common disease in man. A predisposition to the disease is probably inherited as an autosomal recessive trait. About 25% of relatives of diabetics show abnormal glucose tolerance curves as compared to 1% in the general population. Definition: A chronic disease due primarily to a disorder of carbohydrate metabolism, cause of which is deficiency or diminished effectiveness of insulin, resulting in hyperglycemia and glycosuria. Secondary changes may occur in the metabolism of protein, fats, water and electrolytes and in tissues/ organs sometimes with grave consequences.

STAGES OF DIABETES MELLITUS


American diabetics association has divided into Four stages. The four stages and findings are shown ahead in tubular form.

CLINICAL TYPES AMD CAUSES


These are two main groups: (a) Primary (Idiopathic): Constitute major group. Exact cause is not Known; metabolic defect is insufficient insulin which may be absolute or relative.
(b)

Secondary: Constitute minor group. Where it can be secondary to some disease process.

Primary (Idiopathic) Two clinical types: Juvenile- onset diabetes: Now called as Type-I(Insulin dependent)- IDDM. Maturity onset diabetes: Type-II NIDDM- (Non Insulin Dependent).
(a)

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS


Large amounts of glucose may be excreted in urine (may be 90 to 100 G / day in case some cases.) Loss of solute produces osmotic diuresis thus large volume of urine (polyuria). Loss of fluid leads to thirst and polydypsia. Ployphagia : eats more frequently. More fond of sweets. The above symptoms may persist for many months in maturity- onset type- I, further symptoms develop treatment is not started. Tissues including muscles received liberal supply of glucose but cannot use glucose due to absolute or relative deficiency of insulin or transport defect to cells. This causes weakness and tiredness. As glucose cannot be used for fuel, fat is mobilized leading to increase FFA in blood and liver. Increased acetyl COA is diverted for cholesterol synthesis- Hypercholesterolemia and atherosclerosis Xanthomas may develop. Increased ketone bodies leads to acidosis, which leads to hyperventilation (air hunger). If ketosis is serve acetone will be breathed out, giving chateracteristic fruity smell in breath (due to acetone). Along with above, there may be excessive breakdown of tissues proteins. Delaminated amino acids are catabolized to provide energy which accounts for loss of weight Due to ketosis develops anorexia nausea, and vomiting. Continued loss of water and electrolytes increases

Dehydration. Keto acidosis produces increasing drowsiness, leading to diabetic coma in untreated cases.

metabolic changes in diabetes mellitus 1. Hyperglycaemia : occurs as a result of:


Decreased and impaired transpoat and uptake of glucose anto muscles and adipose tissues. Repression of key glycolytic enzymes like glucokinase,phosphofructiokinase and pyruvate kinase takes place. Derepression of key gluconeogenic enzymes like pyruvate craboxxylase, phosphoenol pyruvate carboxykinase, fructose bi-phosphatase and glucose6-phosphatase occur, promoting gluconeogenesis in liver. This fuether contributes to hypergly caemia. Elevated amino acid lenel in tha blood particularly alanine provides fuel for gluconeognesos in Liver. 2. Amino Acids Level: Tranasport and uptake of amino acids in peripheral tissues is also depressed causing an elevated circulating level of amino acids, particularly alanine. Glucocorticoid activity predominate having catabolic action on peripheral tissue proteins, releasing more amino acids in blood. Amino acids breakdown in liver results in increased production of urea N. 3.Protein synthyesis: protein synthesis is decreased in all tissues due to: Decreased production of ATP Absolute or relative deficiency of Insulin. 4. Fat metabolism Decreased extra mitochondrial de novo synthesis of FA and also TG synthesis due to

decrease in acetyl COA form carbohydrates, ATP, NADPH and glycerol-(p) in all tissues. Stored lipids are hydrolyzed by increased Lipolysis liberating free fatty acids (FFA). Increased FFA interferes at several steps of carbohydrates phosphorylation in muscles, further contributing to hyperglycemia.

5. Effect on Glycogen synthesis : Glycogen synthesis is depressed as a result of : Decreased glycogen synthesis activity due to deficiency of Insulin. By activation of phosphorylase production glycogenolysis through the action of epinephrine and or glucagons (antagonistic) hormones. By increased ADP: ATP Ratio.