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Diabetes Why Diabetes? (Superficially) Hyperglycaemic Hormones • Glucagon Hyperglycaemic Hormones • Glucagon • Catecholamines – eg adrenalin • Glucocorticoid hormones – eg cortisol Hyperglycaemic Hormones • Glucagon • Catecholamines – eg adrenalin • Glucocorticoid hormones – eg cortisol • Human Growth Hormone (HgH) Hyperglycaemic Hormones • Glucagon • Catecholamines – eg adrenalin • Glucocorticoid hormones – eg cortisol • Human Growth Hormone (HgH) • Thyroid Hormones Hypoglycaemic Hormones Insulin Types • Type 1A • Type 1B • Type 2 – obese – non obese • Gestational Type 1A • autoimmune condition • strongly linked with HLA - DR3 and HLA DR4 • early onset • Risk – sibling 5% - 10% – offspring 2% - 5% Type 2 • • • • • • • impaired insulin secretion peripheral insulin resistance increased hepatic glucose production late onset associated with long term obesity Approximately 90% are overweight Risk – sibling or offspring 10% -15% Type 2 • Insulin levels can be high, normal or low • Less prone to ketoacidosis • Multiple metabolic imbalances influence insulin action • Adiponectin decreases • Metabolic syndrome Metabolic syndrome Three or more of the following: • Abdominal obesity – waist circumference >88cm in women or 102cm in men • Triglycerides ≥150mg/dL or(1.7mmol/L) • HDL <50mg/dL (1.3mmol/L) in women or <40mg/dL (1.0mmol/L) • Blood pressure >130/85 mm Hg • Fasting plasma glucose >100mg/dL (5.6mmol/L) Gestational • glucose intolerance usually in 3rd trimester • occurs in 2% of pregnancies • 60% develop diabetes mellitus within 15 years Clinical manifestations • Hyperglycaemia • Normal range – Adult 70 - 110 mg/dl or 3.9 - 5.8 mmol/L • And... Three polys • Polyuria • Polydipsia • Polyphagia Polyuria • Glucose not taken up by body cells is filtered at the kidneys • Transport system in kidney can’t reabsorb all • The rest appears in the urine • Osmotically attracts water Polydipsia • Polyuria • ECF volume decreases – BP, renin, angiotensin, aldosterone, ADH • ICF also reduces • Thirst centre in hypothalamus stimulates thirst Polyphagia • Cells use up stores of carbohydrates fats and proteins • Corresponding cellular starvation results in hunger • Not usually present in Type 2 Systemic effects • • • • • Loss of weight in Type 1 Recurrent blurred vision Fatigue Paresthesias Skin infections – Pruritis and vulvovaginitis – Balanitis Acute Complications • Diabetic ketoacidosis • Hyperosmotic hyperglycemic state • Insulin shock Diabetic Ketoacidosis • Body uses fats for energy • Produces ketone bodies which are acidic • “Fruity” breath and urine Acute Complications Diabetic Hyperosmotic Insulin shock ketoacidosis hyperglycemic state Onset 1 - 24 hrs 24 hrs - 2 weeks Sudden Skin Dry, flushed Dry Moist, pale Fever Frequent Hyperthermia Mouth Dry Dry May be hypothermic Drooling Acute Complications Thirst BP Pulse DKA HHS IS Intense Extreme Absent Low Low Normal Weak, rapid Weak, rapid Normal Eyeballs Soft Normal Vomiting Common Rare Other Kussmaul’s +ve Babinski Chronic complications • • • • • Peripheral neuropathy Nephropathy Retinopathy Vascular complications Infections Peripheral Neuropathy • impaired blood supply to nerves • segmental demyelinization process • leading physiologic cause of impotence – 30% - 60% of all diabetics Peripheral Neuropathy • Gastromotility disorders are common – – – – – – Constipation Diarrhea Fecal incontinence Nausea and vomiting Dyspepsia Gastroparesis Nephropathy • basement membrane of glomerulus altered • diabetes is most common cause of renal failure Retinopathy • leading cause of acquired blindness • non proliferative form micro aneurysms – retinal oedema and haemorrhage • proliferative – fragile neovascularisation – scar tissue and adhesions form between retina and vitreous Vascular Complications • macro- and micro-circulation • increased heart disease • peripheral vascular insufficiency – ulceration – infection – gangrene Infections • • • • • Diabetic foot ulcers Osteomyelitis UTIs candidal infections of skin and mucous TB Diagnostics • Fasting plasma glucose – Normal <100mg/dL (5.6mmol/L) • Oral Glucose Tolerance Test – important screening test for diabetes – follow response to amount of concentrated glucose usually at 0.5, 1, 1.5, 2 & 3 hours – normal person is normal in 3 hours Diagnostics • Capillary blood glucose monitoring • Glycated haemoglobin testing – Provides index of blood glucose over previous 6 to 12 weeks – A1C levels <6% are normal.