DIABETES MELLITUS DR HEYAM AWAD FRCPATH DEFINITION DM

DIABETES MELLITUS DR HEYAM AWAD FRCPATH

DEFINITION • DM IS A GROUP OF METABOLIC DISORDERS CHARACTERIZED BY HYPERGLYCEMIA. • HYPERGLYCEMIA CAUSED BY… DEFECTS IN INSULIN SECRETION , INSULIN ACTION OR BOTH. • RESULTS IN DAMAGE IN MANY ORGANS.

DM IS THE LEADING CAUSE OF : • END STAGE RENAL DISEASE. • ADULT ONSET BLINDNESS. • NON TRAUMATIC LOWER EXTREMITY AMPUTATION.

CLASSIFICATION • TYPE 1 DM…ABSOLUTE INSULIN DEFICIENCY DUE TO BETA CELL DESTRUCTION. 10% OF CASES. • TYPE 2 DM… RELATIVE INSULIN DEFICIENCY. . DUE TO PERIPHERAL RESISTANCE TO INSULIN ALONG WITH INADEQUATE COMPENSATORY RESPONSE. • MINORITY OF CASES…SECONDARY CAUSES.

SECONDARY CAUSES • GENETIC DEFECTS IN BETA CELL FUNCTION OR INSULIN ACTION. • EXOCRINE PANCREATIC DEFECTS: CHRONIC PANCREATITIS, PANCREATECTOMY, NEOPLASIA…. • ENDOCRINOPATHIES: ACROMEGALY, CUSHING SYNDROME, HYPERTHYROIDISM. • INFECTIONS: CMV, CONGENITAL RUBELLA, COXSACKIEVIUS B INFECTION. • DRUGS: STEOIDS, THYROID HORMONE. • GESTATIONAL DIABETES.

GLUCOSE HOMEOSTASIS REGULATED BY THREE MECHANISMA… • GLUCOSE PRODUCTION IN LIVER • GLUCOSE UPTAKE BY PERIPHERAL TISSUE. • ACTION OF INSULIN AND GLUCAGON.

• INSULIN INCREASES GLUCOSE TRANSPOT INTO STRIATED MUSCLE AND ADIPOCYTES. • IN MUSCLE …. GLUCOSE IS STORED AS GLYCOGEN OR OXIDISED TO GENERATE ATP. • IN ADIPOCYTES GLUCOSE IS STORED AS LIPID. • ALSO. . INSULIN HAS ANABOLIC EFFECT: INCREASED SYNTHESIS AND DECREASED DEGRADATION OF GLYCOGEN, LIPID AND PROTEIN

• INSULIN REDUCES GLUCOSE PRODUCTION BY LIVER. • THE MOST IMPORTANT STIMULUS OF INSULIN IS GLUCOSE.

TYPE 1 DM • AUTOIMMUNE DISEASE. • ISLET DESTRUCTION. • CLINICAL DISEASE WHEN 90% OF ISLET CELLS DESTROYED. • DEVELOPS IN CHILDHOOD, MANIFEST AT PUBERTY, PROGRESS WITH AGE. • NEED EXOGENOUS INSULIN.

TYPE 2 DM • GENETIC AND ENVIRONMENTAL FACTORS. • TWO METABOLIC DEFECTS: * INSULIN RESISTANCE. * BETA CELL DYSFUNCTION.

INSULIN RESISTANCE • FAILURE OF TARGET TISSUES TO RESPOND TO INSULIN. • ASSOCIATED WITH OBESITY. • RISK OF DM INCREASES WITH INCREAING BMI.

BETA CELL DYSFUNCTION • INABILITY OF BETA CELLS TO ADAPT THEMSELVES TO THE DEMANDS OF PERIPHERAL INSULIN RESISTANCE.

MORPHOLOGICAL CHANGES IN DIABETIC PANCREAS • REDUCTION IN NUMBER AND SIZE OF THE ISLETS. • LEUKOCYTIC INFILTRATION OF THE ISLETS. • AMYLOID REPLACEMENT OF ISLETS. • FIBROSIS.

COMPLICATIONS OF DM • ALL BODY ORGANS AND TISSUES CAN BE AFFECTED. • MAINLY… ARTERIES, KIDNEY, RETINA, NERVES.

VASCULAR DISEASE MACROVASCULAR DISEASE: • ACCELERATED ATHEROSCLROSIS AFFECTING AORTA AND LARGE AND MEDIUM SIZED ARTERIES. • MI IS THE MOST COMMON CAUSE OF DEATH IN DM. • GANGRENE OF THE LOWER LEGS DUE TO ADVANSED VASCULAR DISEASE.

VASCULAR DISEASE • HYALINE ARTERIOLOSCLEROSIS IN SMALL BLOOD VESSELES.

DIABETIC NEPHROPATHY • RENAL FAILURE IS THE SECOND MOST COMMON CAUSE OF DEATH IN DIABETICS. • THREE LESIONS CAN BE SEEN: GLUMERULAR LESIONS, RENAL VASCULAR LESIONS AND PYELONEPHRITIS.

OCULAR COMPLICATIONS • RETINOPATHY. • CATARCT. • GLAUCOMA. • RETINOPTHY IS THE MOST COMMON PATTERN

DIABETIC NEUROPATHY • PERIPHERAL SYMMETRIC NEUROPATHY OF LOWER EXTREMITIES. • AUTONOMIC NEUROPATHY… DISTURBANCES IN BOWEL AND BLADDER FUNCTION. • CAUSED BY: MICROANGIOPATHY OR DIRECT AXONAL DAMAGE