Diabetes Mellitus Presentation PDF

Diabetes mellitus  Introduction Diabetes mellitus is defined as an abnormal metabolic state in which there is hyperglycemia due to absolute or relative lack of insulin.and or insulin resistance The actions of insulin are all anabolic. It promotes the uptake of glucose by cells and the...

Diabetes mellitus  Introduction Diabetes mellitus is defined as an abnormal metabolic state in which there is hyperglycemia due to absolute or relative lack of insulin.and or insulin resistance The actions of insulin are all anabolic. It promotes the uptake of glucose by cells and the formation of intracellular glycogen from glucose. It stimulates cells to utilize amino acids for protein synthesis rather than gluconeogenesis and it promotes the uptake of free fatty acids by adipose tissue. The con- sequences of insulin deficiency are therefore catabolic, that is, there is breakdown of tissue energy stores. Insulin is the only hormone with a hypoglycaemic.effect There are five hormones which tend to exert a hyperglycaemic effect; glucagon, glucocorticoids, growth hormone, adrenaline & noradrenaline. Thus the hyperglycaemic effects of these hormones cannot be counter - balanced if there is inadequate.insulin action The pathophysiology of DM Basic clinical features These follow two pathophysiological situations the plasma hyperglycaemia and the reduction of cellular energy (deficient of intracellular glucose) Hyperglycaemia (above renal threshold which is 180 mg\dl ) results in heavy glycosuria and this leads to an osmotic diuresis and polyuria. Then dehydration, hyperosmolarity and hypovolemia then thirst (polydipsia) Reduction in intracellular energy causes increase in gluconeogenesis and decrease in protein synthesis, so there will be loss of weight. There is also active lipolysis with the result of hyperlipidaemia  fatty liver & increased tendency of atherosclerosis.& angiopathy Acute complications In case of severe reduction of cellular energy, the liver starts to convert excess free fatty acids via acetyl CoA into ketone bodies (acetoacetate, acetone and 3- hydroxybutyrate). These ketone bodies metabolized as alternative sources for cellular energy except for brain tissue. They dissociate to release hydrogen ions, and severe metabolic acidosis may occur. The combination of severe ketosis + acidosis + hyperglycaemia + hyperosmolarity + dehydration and electrolyte disturbance (k+ is low intracellular), results into a state called diabetic ketoacidosis with a degree of cerebral function impairment. The maximum deterioration of this state.is the ketoacidotic coma An other coma (hyperosmolar nonketotic coma), results from massive dehydration and profound hyperglycaemia but without severe.energy reduction so no ketoacidosis Overdosage insulin therapy may cause another coma ( the hypoglycaemic coma). All these diabetic comas are dangerous acute.complications of DM  Classification of diabetes DM * Fully established (completely proved) DM Primary DM IDDM (type one) NIDDM (type two) Secondary DM * Not fully established (not completely proved) DM Gestational DM Borderline DM (glucose intolerance) Primary diabetes mellitus Primary diabetes accounts for about 99% of all cases of diabetes and it caused by two famous forms, type1 (IDDM)and type2 (NIDDM). each of them is defined clinically if the fasting plasma glucose level is greater than 7.8 mmol/l (140 mg/dl) or if the 2-hour postprandial plasma glucose is more than 11 mmol/l(200.mg/dl)  Type 1(IDDM) Type 2(NIDDM) Onset Onset over40years * under40years * * Obese patient Thin patient * * Affects 1 in 40 of Affects 1 in 400 of population population * Liable to * Liable to ketoacid hyperosmolar –otic coma nonketotic coma * Depend on insulin *Does not depend on for therapy insulin for therapy (oral β* hypoglycemic drugs) cells destroyed in * β cells are not pancreas destroyed in pancreas Type 1 Type 2 Absolute lack of * Relative lack or* insulin resistance to insulin * Islet amyloid * Islet amyloid absent * Islet auto- present *Islet cell antibody present auto-antibody absent * * Concordance rate Concordance rate for for monozygotic monozygotic twins twins 40% 100%  Secondary diabetes Sometimes diabetes occurs secondary to certain diseases that associated with hyper secretion of any of the hormones which tend to exert a hyper glycaemic effect. Thus Cushing's syndrome, Phaeochromocytoma, acromegaly glucagonoma of the pancreatic islet cells, and severe thyrotoxicosis may also end with DM. On the other hand the generalized destruction of pancreatic tissues by pancreatitis (acute or chronic), haemochromatosis and occasionally carcinoma may also lead to secondary diabetes. Sometimes the severe liver diseases may be the cause like hepatic cirrhosis and chronic active hepatitis. Some drugs may lead to DM like steroids, oral contraceptives and thiazide diuretics Gestational DM * Gestational diabetes is high blood sugar that develops during pregnancy and usually disappears after delivery. * It can occur at any stage of pregnancy, but is more common in the second half. * It can cause problems for mother and baby during and after birth. But the risk of these problems happening can be reduced if it's detected and well managed.  Prediabetes (Borderline Diabetes) Prediabetes is characterised by the presence of blood glucose levels that are higher than normal but not yet high enough to be classed as diabetes. Prediabetes may be referred to as impaired fasting glucose (IFT), (IFT) if you have higher than normal sugar levels after a period of fasting, or as impaired glucose tolerance (IGT), if you have higher than normal sugar levels following eating. Chronic complications Accelerated atheroma of large blood* vessels Myocardial infarction Cerebrovascular disease Ischaemic limbs *Endothelial cells and basal lamina damage of small vessels (angiopathy) Nephropathy (Diabetic glomerulosclerosis) that may  chronic renal failure Retinopathy that may  blindness *Neuropathy of peripheral nerves This may also be due to disease of small vessels which supply the nerves  abnormal sensations Impairment of neutrophils function +* Media of blood sugar Increase the susceptibility of bacterial infection e.g. boils, carbuncles & U.T.I *Gangrene of extremities Atheroma, diabetic microangiopathy, and increase susceptibility to infections all tend to promote occurrence of diabetic foot ulcer (diabetic septic foot) *Complications with pregnancy High incidence of preeclamptic toxae- mia (PET), large babies + difficult labor and neonatal.hypoglycaemia Laboratory diagnosis 1. Urine for glucose is +ve (helps in screening) It may be negative 2. Urine for ketone bodies may be +ve (important in ketoacidosis diagnsis). 3. Fasting (over night fasting) venous blood glucose more than 140mg/dl is diagnostic. 4. Post-prandial blood glucose (taken 2hrs after CHO meal 75 g) more than 200mg/dl is diagnostic. 5. Oral glucose tolerance test (OGTT); not indicated except in certain situations e.g. the borderline fasting, or post-prandial, blood glucose and gestational diabetes. 6. Random blood glucose not diagnostic unless it was more than 200mg/dl (indicated in emergency situations e.g. a comatose patient). 7. Glycated Hb (HbA1c) one of the Long term indices of diabetic control (last three months) ( normally < 6.5%)  The actions of the main antidiabetic oral drugs Metformin Decrease glucose absorption Reduce glucose synthesis in liver Increase insulin sensitivity and action Glibendamide Stimulate the secretion of insulin Reduce glucose release from liver Increase insulin sensitivity and action Gliclazide Stimulate the secretion of insulin