Diabetes Mellitus PDF

Diabetes Mellitus • Characterised by persistent hyperglycaemia • Normal values for blood glucose : 4.0-6.0 mmol/l • Values for blood glucose in excess of 50 mmol/l have been recorded for some patients ! • Huge financial burden for the NHS. 1 Diabetes Care Areas 2 WHO Diabetes Poster World Heal...

Diabetes Mellitus • Characterised by persistent hyperglycaemia • Normal values for blood glucose : 4.0-6.0 mmol/l • Values for blood glucose in excess of 50 mmol/l have been recorded for some patients ! • Huge financial burden for the NHS. 1 Diabetes Care Areas 2 WHO Diabetes Poster World Health Organisation Report published in 2016 Data collected in 2014. 3 Getting the academic level correct 4 Getting the academic level correct (2) 5 The Stats…. 6 The UK Picture Diagnosed Diabetes (2015) England Wales Scotland Northern Ireland Total 2.9 million 0.2 million 0.3 million 0.1 million 3.5 million BUT, it is estimated that there are 1.1 million undiagnosed individuals living with diabetes. So, there could be 7% of the UK population living with diabetes mellitus ! 7 Type 1 or Type 2 Diabetes Mellitus Adults Children • 10% Type 1 DM • 90% Type 2 DM • 9% of population with diabetes • 95% Type 1 DM • 2% Type 2 DM • 3% MODY (Maturity Onset Diabetes of the Young) • 56% Male / 44% Female • 2000 – first cases of Type II DM seen in children 8 Type 2 DM Prescribing in England 9 Diabetes and Insulin How is insulin involved in the regulation of the concentration of glucose in the blood ? 10 Blood Glucose Balance Glucose Homeostasis Normoglycaemia 11 Overview of glucose homeostasis 12 Glucose homeostasis following meals 13 CONTROL OF BLOOD GLUCOSE (negative feedback) Plasma glucose 4.5-5.2 mmol/l (fast) or <8mmol/l (random) Hypoglycaemia Low blood glucose • Glucagon release (α ) • Liver cells (hepatocytes) release glucose Higher blood glucose Hyperglycaemia High blood glucose • Insulin release (β) • Glucose enters cells Lower blood glucose 14 How does the beta cell know when to release insulin? (Stimulus-secretion coupling) Glucose enters β cell; phosphorylated; Glycolysis, pyruvate formed; ATP produced; K channel closes, K+ rises in cell; membrane depolarisation; calcium channel open; Calcium rises in cell; insulin granule exocytosis 15 Post lecture exercise – use the notes below to write a full paragraph to describe how elevated glucose concentrations cause the secretion of insulin Glucose enters β cell; phosphorylated; Glycolysis, pyruvate formed; ATP produced; K channel closes, K+ rises in cell; membrane depolarisation; calcium channel open; Calcium rises in cell; insulin granule exocytosis 16 What happens when insulin binds to it’s receptor? 17 Post lecture exercise – watch the recorded version of the lecture to write a paragraph describing how insulin increases the uptake of glucose into cells. 18 Why do individuals have diabetes ? Type 1 DM (IDDM) Type 2 DM (NIDDM) • Mainly due to autoimmune mediated destruction of pancreatic b-cells which results in absolute insulin deficiency. • Characterised by insulin resistance in the tissues . • Environmental or viral trigger • Weak family trait (concordance risk for identical twins = 40%), contracted at a young age (9-13 yrs) • Can only be treated by insulin administration (sub-cutaneously) or pancreas transplant • Associated with over nutrition, obesity, lack of exercise. • Metabolic syndrome • Strong family trait. • Environmental and genetic • Onset - > 40 years old 19 Treatment of Type 2 Diabetes mellitus Treatment: • Reduce calories, carbohydrate, lipids, exercise. • Sulphonylureas – β cells secrete more insulin • Bariatric surgery – weight loss surgery. Laparoscopic adjustable gastric banding (LAGB). • And others… pp 324-327 Ahmed Ahmed 2nd edition p 316-7, 324-327 20 Diagnosis of diabetes mellitus • Urine glucose test –>10mmol/l glucose, overspill. GLYCOSURIA Gaw 64; Ahmed p 311 • HbA1c – see later • Blood glucose • Fasting blood glucose (FBG) 4.5-5.2 mmol/l normal >7 mmol/l = diabetic (6.0 – 6.9 mmol/l = impaired fasting glycaemia) • Random blood glucose (RBG). <8 mmol/l normal; >11.1 mmol/l suggests diabetes mellitus. Must be checked with FBG. • Oral glucose tolerance test (OGTT) – next… 21 Oral glucose tolerance test (OGTT) 1. 2. Baseline FBG Oral 75g glucose in 300ml water in 5 mins. 3. Measure plasma glucose every 30 mins for 2 h (or just at 2h). Diagnostic of diabetes if 2 h [glucose] reading • > 11.1 mmol/l Impaired glucose tolerance • 7.8 – 11 mmol/l BUT – often not carried out correctly. WHO advocate FBG for diagnosis. 22 Patient Management Blood Glucose • Several techniques : (a) Spectrophotometrically (b) Dry Chemistry (multilayer film analyisis) (c) Glucose meter (modified O2 electrode) • Point of care and home monitoring now taking over from traditional laboratory analysis 23 Glycated Haemoglobin (HbA1c) Patient Management (cont.) • Normally only 5% HbA is glycated (HbA1c) • As the plasma glucose concentration rises, more HbA becomes glycated and the percentage present as HbA1c increases. • As the half life of a RBC is approx. 60 days, monitoring the HbA1c content provides us with a 1-2 month plasma glucose “history”. • Poorly controlled diabetes i.e. high HbA1c, leads to a range of complications including nephropathy and retinopathy. • Each laboratory has its own reference range. For example, at Hope Hospital : HbA1c < 6% Normal, < 7.5% Good control 7.5 – 8.9% Moderate control> 9% Poor control • Limitations: Other conditions also show HbA1c elevations e.g. opioid and alcohol abuse, iron deficiency anaemia 24 The new units for HbA1c = mmoles/mole 25 Long term effects of diabetes 26 Neuropathy Defective blood supply to neurons Axon degeneration Loss of sensation No removal from source of pain -repeated damage Diabetic trophic ulcers Ischaemia in feet – poor healing 27 Nephropathy Atherosclerosis – aorta and renal arteries nephron ischaemia Hyaline arteriolosclerosis thickening of glomerular capillary basement membrane • Glycation of proteins Expansion of the mesangial matrix Glomerular damage• Increase in permeability • Proteinuria – renal failure • microalbuminuria 28 Complications of Heart and Brain Retinopathy Hyaline arteriolosclerosis basement membrane thickening in retinal blood vessels •Retinal haemorrhage Cataracts Glucose attaches to lens proteins Cloudiness 30 Impact of diabetes on pathology services……… 31 Summary of tests All Patients with DM Oral glucose tolerance test/Fasting glucose HbA1c Hyperglycaemia Blood glucose Hypoglycaemia Ketones, Us & Es Type 1 DM Type 2 DM Nephropathy Us & Es Myocardial Troponin Creatinine Clearance Infarction FABP Microalbumin CK (Atherosclerosis) Myoglobin Total lipid profile (TGs, LDL, HDL) Neuropathy CRP (+ other acute phase proteins) PCT Retinopathy N/A Cerebrovascular Accident (Atherosclerosis) Total lipid profile (TGs, LDL, HDL) 32