Diabetes mellitus Acute and chronic complications

1. Diabetes mellitusAcute and chronic complications

2. Definition of diabetes mellitus Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.

3. Classification of diabetic syndromes • Type 1 diabetes mellitus (10 %) autoimmune and idiopathic • IDDM, juvenile diabetes • Type 2 diabetes mellitus (90 %) • NIDDM, adult type • Other types of diabetes mellitus (rare, long list) • Gestational diabetes mellitus (temporary dg.) impaired glucose tolerance and impaired fasting glucose are RISK FACTORS And where is LADA and MODY ?

4. LADA latent autoimmune diabetes of adulthood • late-onset autoimmune diabetes of adulthood • slow onset type 1 diabetes, or • type 1.5 (type one-and-a-half) diabetes • slow-onset Type 1 autoimmune diabetes in adults • age more than 35 years • MODY maturity onset diabetes of the young • several hereditary forms of DM caused by autosomal dominant mutations of genes (MODY 1 – 9) • early manifestation • positive familiar history • various types, most commonly acts like a very mild version of • type 1 DM

5. Other types of DM • genetic mutations • diseases of exocrine pancreas (chronic pancreatitis) • excessive secretion of insulin-antagonistic hormones • induction of DM by drugs or chemicals (alloxan, streptozotocine) • ... • Gestational DM • DM during pregnancy - resembles type 2 diabetes • about 2%–5% of all pregnancies, may improve or disappear after delivery • about 20%–50% of affected women develop type 2 diabetes later in life • untreated gestational diabetes - damage the health of the fetus - macrosomia, congenital cardiac and central nervous system anomalies, skeletal muscle malformations, respiratory infant syndrome...

6. Basic Thirst Polyuria Weight loss Fatigue Other Muscle cramps Obstipation Blurred vision Fungal and bacterial infections If you do not begin insulin therapy immediately nausea, vomitus abdominal pain dehydration Kussmaul breathing acetone smell of breath ketones in blood, urine, acidosis COMA DIABETICUM Symptoms of diabetes mellitus

8. Symptoms of DM NOTHING Type 2 for long time (months, years) Hypertension Myocardial infarction, stroke with very bad prognosis Microangiopathic complications (amputation) Gestational diabetes mellitus Screening! Harmful both for baby and mother

9. Diagnostic criteria of DM • symptoms of DM • casual glucose concentration > 11 mmol/l • fasting glycaemia > 7 mmol/l • glycaemia 2h after 75 gof glucose > 11 mmol/l • symptoms of DM and 1 abnormal blood glucose • two abnormal BG values on 2 days • fasting glycemia 5,6 – 6,99 = impaired fasting glycaemia, pre-diabetes • glycaemia in oGTT after 2 hod 7,8 – 11,0 = impaired glucose tolerance

10. Acute complications of DM

11. Diabetic hypoglycaemia • glycaemia lower than 3,5 mmol/l Cause • higher dose of insulin or PAD (sulfonylurea) • inadequate food intake Symptoms • vegetative – sweating, palpitations, anxiety, shakiness, pallor • neuroglycopenic – confusion, weakness, atypical behaviour, impaired concentration, sleepeness, double vision, incoordination, dificulty speaking • other – hunger, nauzea and vomiting, headache

12. Hypoglycemia

13. Diabetic ketoacidosis • acute complication predominantly of type 1 DM • inadequate or no therapy with insulin Mechanism • the absence of insulin  release of free fatty acids from adipose tissue  converted in the liver into ketone bodies (acetoacetate, acetone, b-hydroxybutyrate)  metabolic acidosis  diabetic coma

14. Diabetic ketoacidosis Symptoms • nausea, vomiting, abdominal pain • polyuria, polydipsia, hyperglycemia, dehydratation • hyperventilation (Kussmaul respiration) • tachycardia, hypotension • acetone smell of breath • MAC – pH, AG

15. Nonketotic hyperosmolar state • nonketotic hyperglycemic hypeosmolar coma • DM type 2 Mechanism • hyperglycemia  hyperosmolarity  polyuria  dehydratation • the presence of some insulin inhibits lipolysis – no ketoacidosis Symptoms • hyperglycemia, hyperosmolarity • dehydratation – hypotension • renal insuficiency, mental and neurologic signs, trombosis • coma, death

16. Lactate acidosis • diabetic pseudohypoxia  increased lactate concentration Symptoms • dyspnea • abdominal pain • MAC (lactate acidosis) • unconsciousness

17. Chronic microvascular complications of DM

18. The main mechanisms Microangiopathy • an angiopathy of small blood vessels • hyperglycemia  damage of endothelial cells, basement membrane grow thicker and weaker Polyol pathway • sorbitol-aldose reductase pathway • decrease of reduced NADPH and oxidized NAD+  diabetic pseudohypoxia

20. The main mechanisms Glycation • hyperglycemia  higher non-enzymatic glucation of proteins • Advanced Glycation End products (AGEs) are the result of a chain of chemical reactions after an initial glycation reaction Effect • aging and some age-related chronic diseases • in DM - increasing vascular permeability, inhibition of vascular dilation by interfering with NO, oxidising LDL... • they bind to receptors for AGE (RAGE on endothelial cells, smooth muscle cells, cells of immune system) - contribute to age- and diabetes-related chronic complications

21. Diabetic retinopathy • damage of the vessels of the retina • the most frequent cause of blindness in developed countries Mechanism • endothelium damage, thickening of basal membrane • changes of osmotic pressure, haemorrhage, microaneurysms, • deposition of proteinand lipid exsudates, • oedema of macula Other complications • cataracta • glaucoma • disorders of refrakction and motility

22. Diabetic retinopathy

23. Diabetic nefropathy • angiopathy of capillaries in the kidney glomeruli • ischemia Symptoms • microalbuminuria (30 – 300 mg albumin/day) • kidney failure • oedema

24. Diabetic neuropathy • angiopathy of vasa nervorum (small blood vessels that supply nerves) sensorimotor neuropathy • sensitivity disorders – pain, heat, cold, pressure vegetative neuropathy • changes in sweating • urogenital dysfunction • gastroparesis, nausea, diarhea, constipation • tachycardia, hypotonia diabetic foot

25. Diabetic foot • ulcer, • infection, • gangrene... • amputation

26. Diabetic footRisk factors

27. prevention

28. Chronic macrovascular complications of DM

29. Atherosclerosis • ...one of the previous seminars...