Diabetes 2023_BB - Tagged.pdf

Diabetes mellitus  Overview Definition Classification Pathogenesis Treatment Acute complications Chronic complications  Diabetes: definition ‘diabetes’ => to run through/ a siphon ‘mellitus’ => honey  variety of conditions diabetes mellitus:  different aetiologies...

Diabetes mellitus  Overview Definition Classification Pathogenesis Treatment Acute complications Chronic complications  Diabetes: definition ‘diabetes’ => to run through/ a siphon ‘mellitus’ => honey  variety of conditions diabetes mellitus:  different aetiologies sweet urine  Metabolic derangement due to: relative or absolute insulin deficiency  a class of disease  chronic hyperglycaemia  associated with disordered metabolism  major vascular complications  specific microvascular complications  Pancreas Islet of Langerhans Pancreatic Delta cell acini Insulin Alpha Red blood cell cells Beta cell Glucagon  Insulin Action Insulin binding to receptor of => 2nd messenger release to facilitate glucose entry into cell insulin  Stimulated Stimulated by PANCREAS by high blood low blood glucose glucose INSULIN GLUCAGON Antagonistic Lowers blood Raises blood glucose glucose Effects of LIVER Insulin & Glucagon FAT MUSCLE Diabetes:  Classification  Insulin-dependent DM or type I absolute need for insulin therapy  Non-insulin-dependent DM/Type II commonest form may progress to IDDM  Gestational diabetes  Malnutrition-related DM  MODY (maturity onset diabetes of the young) autosomal dominant inheritance, < 25 yrs old  Secondary to:  pancreatic disease (chronic/recurrent)  other endocrine disease (Cushing’s syndrome)  drugs (corticosteroids)  abnormalities of insulin/insulin receptor  genetic syndromes - cystic fibrosis  Pathogenesis & Treatment IDDM- type I  genetic predisposition  autoimune destruction of Beta cells  environmental factors: viruses/chemicals  insulin injections, diet NIDDM- type II  multifactorial inheritance  ?downregulation of insulin receptors/ reduced response to insulin  Dietary management  Worsened condition: oral hypoglycaemic agents i) sulfonylureas - stimulate insulin production ii) metformin - inhibition of liver glucose prodn  INSULIN-DEPENDENT : Type I Juvenile onset, < 20 years sudden, severe onset normal body weight energy => ketone bodies (acetoacetic acid/b-hydroxybutyric acid) => metabolic acidosis in blood  Hyperglycaemia  Glycosuria => fluid & electrolyte imbalances  Non-insulin-dependent: Type II Maturity onset, >30 years (10% of 65+ yrs) Gradual, subtle onset 80% = overweight >60% familial No HLA association No islet cell autoantibodies Islet lesions: tissue fibrosis, amyloid Normal/slightly reduced B cells Normal blood insulin  Insulin receptor NIDDM - Type II  Heterogeneous disorder  ? impaired insulin secretion  reduced tissue sensitivity to insulin Glucose Obesity Non-diabetic Hypertension Environmental factors   Insulin receptors intracellular inhibition of signalling Glucose Hyperglycemia NIDDM  Diabetic complications  severity and duration of hyperglycemia  level of glycaemic control => ACUTE/CHRONIC Protein Glycosylation glycation products => stable AGEs  inactivate protein  vascular BM thickening Polyol Pathway  increased glucose uptake  sorbital accumulation  Acute Complications  Hypoglycemia  30% IDDM patients  unconciousness  Shaking, sweating, rapid heartbeat  Hunger  Headache  Sudden moodiness  Behavior changes, confusion, lack of coordination  Acute Complications  Ketoacidosis  death in 2.5%  any age, common in young  precipitated by: infection or illness, omission of insulin  Hyperosmolar non-ketoacidotic coma  death in 15%  middle-age +, undiagnosed NIDDM  severe hyperglycaemia, dehydration, lethargy Symptoms of Diabetes  Other complications:  Reduced immune and poor healing response  hyperglycemia  reduces the function of immune cells  increases inflammation  bacterial and fungal infections e.g. respiratory infections  Bacterial & Fungal Infections Necrobiosis lipoidica diabeticorum:  mostly in women  severe necrobiosis  ulceration  Chronic complications Diabetic macrovascular disease:  Cardiovascular disease Diabetic retinopathy  Peripheral vascular disease  Diabetic Foot Cataract Diabetic microvascular disease Glomerulosclerosis Coronary Diabetic neuropathy atherosclerosis Necrotising Diabetic nephropathy papillitis Diabetic cardiomyopathy Autonomic dysfunction: Diabetic retinopathy diarrhoea Other common ocular Focal Occlusive complications: Cataracts demyelination atherosclerosis Foot: ulcers, gangrene  Major vascular disease Atherosclerotic lesions - blood vessel occlusion Cardiovascular disease: Coronary artery disease - angina/MI Vascular insufficiency: Brain – infarcts calcium atheroma Legs - ulcers, gangrene in toes/feet  Diabetic Foot ulceration Ischaemia gangrene  Diabetic Microvascular Disease  increased thickness of capillary BM  arteriolosclerosis  vascular occlusion/compromised blood flow defective healing in chronic ulcers major complications in Collagen kidney & retina Smooth muscle cell  nerve damage Endothelial cell Fibroblasts  Diabetic Nephropathy  renal failure occurs in 30-40% IDDM & few NIDDM  increases with severity & duration  Necrotising papillitis  Diabetic glomerulosclerosis Papillary necrosis: acute pyelonephritis 2o to urinary infection  Diabetic glomerulosclerosis (Kimmelstiel-Wilson disease)  end-stage renal disease; chronic renal failure  1/3 renal transplants  sclerosis of kidney glomeruli: BM changes renal hyperperfusion Glomerular lesion Non-diabetic Diabetes  NEG of BM  progressive accumulation of BM  increased mesangial cells  enlarged glomeruli  microangiopathy Proteinuria > 0.5g/day  Diabetic neuropathy  disease duration: 40% post 20 years Non-diabetic Diabetic  ed sensation  muscle weakness, atrophy, wastage Pathology thickened capillaries ischaemia glycosylated nerve proteins axonal degeneration loss of myelination  reduced conduction velocity 3rd cranial nerve palsy:  ptosis Autonomic function Common Ocular Complications Cataracts Diabetic retinopathy (DR)  retinal ischaemia: NORMAL DIABETIC Microaneurysms Endothelial cell : Pericyte Ratio 1:1 >1;1 endothelial cell Obliterated capillary pericyte network Microaneurysms + haemorrhage Pericyte loss microaneurysm Microaneurysms Narrowed lumen Retinal capillary + haemorrhage endothelial vacuolated, thickened BM + exudates cell Proliferative DR: sight-threatening Pericyte BM Loss of pericyte  Background Diabetic Retinopathy Scattered microaneurysms Ischaemic Dot haemorrhages Large blot haemorrhages  Serious Diabetic Retinopathy Background Peripheral Proliferative Cotton wool spots Venous changes: Hard exudates beading Haemorrhages vessel breakage End-stage Diabetic Retinopathy:  uncontrolled new vessel growth  fibrous tissue contraction  retinal traction  retinal detachment  visual loss DIABETES: