GLUCOSE METABOLISM Blood glucose * Normal blood glucose: 3,3 - 5,6 mmol/l * Hyperglycaemia: > 5,6 mmol/l 45,7 - 7,0: impaired fasting glucose 4> 7,0: diabetes mellitus * Hypoglycaemie: < 3,3 mmol/l Hypoglycaemia - symptoms * Autonomic symptoms (< 3.0 mmol/l) 4 counterregulation hormone secretion Adrenalin 4Sweating, tremor, sensation of hunger * CNS symptoms (< 2.2 mmol/l) 4Inadequate supply of the brain with glucose 4Impaired cognitive function, unconsciousness Causes of fasting hypoglycaemia * Drugs 4Insulin, oral hypoglycemic drugs * With c-peptide level 4Insulinoma * With normal c-peptide level 4Lack of insulin antagonists Cortisol, growth hormone, glucagone, thyroxin 4Lack of precursors of glucose Uraemia, sepsis, hepatic coma, kachexia, glycogenosis ˇ Dumping syndrome 42-4 hours after food intake 4Gastrectomy (Billroth II) * Inherent diseases 4Hereditary fructose intolerance 4Galactosemia Causes of postprandial hypoglycaemia ˇ Fasting > 5.6 mmol/l) * Postprandial > 11.0 mmol/l * Asymptomatic 45.7 - 11.0 (approx.) * Symptomatic 4> 11 mmol/l - glycosuria Hyperglycaemia - symptoms Hyperglycaemia - couses * Diabetes mellitus type 1 4Autoimmune - destruction of -cells in pancreas 4Idiopathic * Diabetes mellitus type 2 (insulino-resistance) 495% of diabetics * Diabetes mellitus in pregnancy * Other types of diabetes * Border-live glucose disorders 4Impaired glucose tolerance 4Impaired fasting glucose Other types of diabetes * Pancreas diseases 4 Pancreatitis, pancreatectomy * Liver disease 4 Chronic hepatitis, cirrhosis * Hereditary hemochromatosis * Endocrine diseases (hypersecretion of insulin antagonists) 4 Acromegaly (growth hormone) 4 Cushing sy. (glucocorticoides) Chronic glucocorticoide therapy 4 Hyperthyreoidism 4 Glucagonoma (glucagon) Diagnostic DM * Glycaemia - only 1 laboratory analysis 4Fasting glycaemia > 7,0 mmol/l 4Postprandial glycaemia > 11,0 mmol/l 4+ typical symptoms Polyuria, thirst, weight loss * Glycaemia - at least 2 laboratory analysis 4The same, but without clinical symptoms * Glucose tolerance test Glucose tolerance test (GTT) * When to do it ? 4Fasting glycaemia 5.7 - 7.0 mmol/l * When not to do it ? 4Fasting glycaemia > 7.0 mmol/l * How to do it ? 475 gr. of glucose p. o. 4Glycaemia: before, after 2 hours Glucose tolerance test (GTT) * IGT 4Fasting gl. 5.7 - 7.0 mmol/l 42 hours 7.0 - 11.0 mmol/l * DM 4Fasting gl. > 7.0 mmol/l 42 hours > 11.0 mmol/l * IFG 4Fasting gl. 5.7 - 7.0 mmol/l 42 hours 7.0 mmol/l Metabolic disorders in DM Insulin * Anabolic hormone 4Secretion mainly after meal * Metabolism of 4Glucose 4Lipids 4Proteins 4Minerals 4Water Insulin and glucose * Uptake of G in the liver * Synthesis or degradation of glycogen * Gluconeogenese * Uptake of G into cells 4Muscle cells, adipocytes DM and glucose * Lack of insulin or insulinoresistance * Hyperglycaemia 4 gluconeogenesis 4 synthesis of glycogen 4 degradation of glycogen 4 liver uptake of G from the portal blood 4 uptake of G by muscle and adipose cells Insulin and lipids * Insulin lipoprotein lipase activity 4Vascular endothelium * Insulin deficiency or insulinoresistance 4 activity of LPL 4Triglycerides are not split off from VLDL 4Hypertriglyceridemia occurs Insulin and lipids * Insulin activity of hormone sensitive lipase (HSL) 4HSL - in the adipocytes (tissue lipase) * Insulin deficiency 4 activity of HSL 4Splitting off triglycerides, fatty acids are released in to the circulation 4Liver: ketone production Ketoacidosis, ketonuria Insulin and proteins * Insulin stimulates 4Transport of aminoacids to the cells 4Synthesis of proteins * Insulin deficiency 4Catabolism of the proteins is induced 4Aminoacids are released and transported to the liver Glucoplastic aminoacids glucose, enhanced hyperglycemia Ketoplastic aminoacids ketoacids, enhanced ketoacidosis Insulin and water * Osmotic diuresis results in massive water losses * Other water loss 4Hyperventilation 4Vomiting * The results of water loss 4Hypovolemia, hypotension 4Hypoperfusion of kidney Insulin and mineral metabolism * K and insulin deficiency 4K is released from the cells 4Hyperkalemia 4K in urine 4K deficit may be up to 5-10 mmol/kg body weight * Na 4Osmotic diuresis = massive Na loss * Osmolality 4 (water loss, hyperglycaemia) Laboratory tests in diabetic patients Laboratory tests in diabetic patients * Glykosuria 4Only for ,,self monitoring" 4No significant for treatment nor for diagnosis * Ketonuria (ketone bodies in the urine) 4Sign of diabetes decompensation 4Self monitoring Laboratory tests in diabetic patients * HbA1c - Glycated hemoglobin 4The ,,average blood glucose concentration" during the preceding 6-8 weeks 4< 4.5 % * C-peptide 4Indicator of the insulin secretion DM type 1 x DM type 2 Hyperinsulinaemia, insulinoresistance 0.7 - 2.0 g/l ˇ Microalbuminuria 4Albumin excretion in the urine 4An early indicator of diabetic microangiopathy, especially diabetic nephropathy 430 - 300 mg/24 hours 42 x a year * Blood lipids 4Cholesterol, triglycerides 4Risk of diabetic macroangiopathy, CHD Laboratory tests in diabetic patients