Diabetes mellitus Definition of DM Fasting glycaemia in venous blood  7 mmol/l • Frequency in general population 5 % • Czech population: 10 %! • 90 % = DM type 2 Diabetes mellitus Diabetesmellitus Primary DM type 1 DM type 2 Pregnancy DM MODY LADA Secondary DM type 1 • IDDM (insulin dependent DM) • without any production of insulin • Fast progression, ketoacidosis • Children, adolescents (7-10 % from all diabetics) • genetic predisposition (defective expression of HLA antigens + T lymphocyte reaction) • Inflammation, viral infections • Antibodies – Beta cells (ICA – Islet Cells Ab) – Insulin (IAA - Inzulin AutoAb) • Ther.: insulin. DM type 2 • Adults, old people • Partial production of insulin • inzulin resistance (defective transport of signal inside the target cell) • Ther.: PAD + insulin Pregnancy DM, MODY, LADA Pregnancy DM (effect of placental hormones) MODY (Maturity Onset Diabetes of the Young) • Young people • Inherited (causal genes are known) • Defective secretion of insulin from beta cells LADA (Late Autoimmune Diabetes of Adult) • DM of adults with auto-antibodies (ICA, IAA) Secondary DM • Afer pancreatectomy (i.e. due to cancer) • Chronical pancreatitis = destruction of functional tissue • Very unstable type of DM (destroyed also cells producing glucagon) • Therapy with insulin • Exocrine pancreatic insufficiency as well Prediabetes Glycaemia • fasting: 5,6 - 6,9 mmol/l (IFG) • After 2 hrs: 7,8 - 11,0 mmol/l (IGT) Making the diagnose of DM Glycaemia – one sample Glycaemia – two samples Oral glucose tolerance test Glycaemia – taken once • Fasting glycaemia  7,0 mmol/l • Post-prandial glycaemia  11,0 mmol/l • + typical clinical symptoms (polyuria, polydypsia, losing weight) Making the diagnose of DM Glycaemia – one sample Glycaemia – two samples Oral glucose tolerance test Glycaemia – two blood samples Taken repeatedly during time • Fasting glycaemia  7,0 mmol/l • Post-prandial glycaemia  11,0 mmol/l • Clinical symptoms don´t have to be present to make diagnosis Making the diagnose of DM Glycaemia – one sample Glycaemia – two samples Oral glucose tolerance test OGTT Indication • Fasting glycaemia up to 6.9 mmol/l Contraindication • Fasting glycaemia  7 mmol/l • Acute disease • till 6 weeks after surgery • Fever • Menstruation How to prepare the patient • 3 days prior the test ordinary intake of sacharides • Avoid of any physical exercise • 24 hrs prior the test don´t drink any alcohol beverages (including beer) • 10-14 hrs. prior the test avoid smoking • 10-14 hrs. be fasting before starting OGTT • Drink only pure water OGTT • Venous blood sample („fasting“ sample) • Drink standard amount of sweetened liquid (75 g of glucose in 250 ml of water) • Relax for 2 hrs. • During the test don´t eat, drink, smoke • 2nd blood sample after 2 hrs. OGTT Evaluation (non-pregnant, men) Glucose Interpretation (mmol/l) Without DM Pre -DM Diabetes mellitus Fasting < 5,6 5,6 - 6,9 IFG ≥ 7,0 in 2 hrs < 7,8 7,8 - 11,0 IGT ≥ 11,1 OGTT – pregnant • DM in pregnancy → fetal and maternal complications • Perform between 24th – 28th week of pregnancy • Same preanalytical conditions • Same dosis of glucose • Blood samples: 0 – 1 – 2 hrs. • Worse tolerance Evaluation (pregnant) Without DM in pregnancy Fasting glucose < 5,1 mmol/l Pregnancy DM Fasting glucose ≥ 5,1 mmol/l Pregnancy DM Glucose after 1 hour ≥ 10,0 mmol/l Pregnancy DM Glucose after 2 hrs. ≥ 8,5 mmol/l Presence of glucose in urine is not important in diagnostic process. DM under control Fasting glycaemia • Measured by M.D. • Patients by themselves („self monitoring“) Post-prandial glycaemia (in 2 hrs after food) Glycemic profile Continuous measuring of blood sugar Glycosuria • Glycosuria is present if the blood sugar exceeds approx. 10 mmol/l for 15 mins. Highly individual • Only self monitoring, not for making diagnose Ketonuria • Is not recommended for making the diagnose Non – enzymatic glycation of proteins Glucose is binding to proteins without presence of enzymes. 2 phases of reaction: • reversible (Schiff base) • irreversible (Amadori product) AGEs = advanced glycation endproducts - lead to vessel damage Glycated hemoglobin (HbA1c) Globin = protein contained in erythrocytes, 3 derivates • HbA1a • HbA1b • HbA1c = stable fraction • Average glycaemia during last 8-12 weeks • Lifetime of ery: 100-140 days (average: 120 ± 10 days) Results Results in mmol/mol • < 42 physiological ranges • 43 - 53 +- compensated DM • > 53 poorly compensated DM Tests for secretion of insulin • Insulin • C-peptide Insulin like a marker • Non - stable • It is impossible to distinguish endogenous insulin and insulin applied artificially • Passing through liver – quick destruction C-peptide (connecting peptide) • -cells of pancreas produce proinsulin • C peptide is not contained in exogenous insuline (medication) • Only own production of insulin C-peptid Marker of endogenous insulin secretion • Normal ranges: 1,1 - 4,4 g/l Acute complications of DM Hyperglycaemia Ketoacidosis Diabetic coma Hyperglycaemia • Rises up the blood osmolarity • Water is going from ICF to ECF • Exceeded renal „treshold“ for glucose = osmotic diuresis → dehydration, feeling thirsty • When treating serious hyperglycaemia with MAc, the kalemia has to be controlled regularly! (relation between potassium and pH!) • Substitution of hypokalemia, lot of infusions Ketoacidosis • DM type 1 • Normal situation: insulin inhibits lipolysis • Pathological situation: insulin is missing ↓ → hyperglycaemia + lipolysis → production of ketoacids → decreasing of pH → MAc, Kusmaull´s breathing Ketoacids Drunk or diabetic? Keto-substances smells similarly to alcohol (mainly aceton) Diabetic coma During hyperglycaemia (deficit of insulin→ MAc) • Due to hyperosmolarity of ECF, the water moves from nerve tissue to ECF • Treating of serious hyperglycaemia has to be very slow. If the glycaemia is decreased too quickly, then the brain edema can occur. During hypoglycaemia (too much of insulin applied or food intake was missed/forgotten) Late complications of DM • Macroangiopathy (atherosclerosis) – Lipids (apolipoproteins) • Mikroangiopathy – Nephropathy – Neuropathy – Retinopathy Mechanism of vessel injury: glycation of proteins Albuminuria = low concentration of albumin in urine • Physiological: < 30 mg/day • Diagnosic strips: > 150 mg/l • MAU: 30-300 mg/day • early indicator of diabetic nephropathy • should be taken every 6 months Results of albuminuria (MAU) Normal excretion microalbuminuria Proteinuria Collection of urine during 24 hrs < 30 mg/day 30 - 299 mg/day ≥ 300 mg/day Timed sample < 20 g/min 20 - 200 g/min > 200 g/min Random sample** (ACR) < 2,5 (M) < 3,5 (F) g/mol creat. 2,5 - 30 3,5 - 30 g/mol creat. 30 g/mol kreat. ** second morning urine. ACR = Albumin/Creatinin Ratio