Diabetes mellitus Acute and chronic complications

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.

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.) And where is LADA and MODY ? impaired glucose tolerance and impaired fasting glucose are RISK FACTORS

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

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...

Symptoms of diabetes mellitus 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 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

Diagnostic criteria of DM symptoms of DM casual glucose concentration > 11 mmol/l fasting glycaemia > 7 mmol/l glycaemia 2h after 75 g of 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

Acute complications of DM

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

Hypoglycemia

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,  -hydroxybutyrate)  metabolic acidosis  diabetic coma

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

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

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

Chronic microvascular complications of DM

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

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

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 protein and lipid exsudates, oedema of macula Other complications cataracta glaucoma disorders of refrakction and motility

Diabetic retinopathy

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

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

Diabetic foot ulcer, infection, gangrene... amputation

Diabetic foot Risk factors

prevention

Chronic macrovascular complications of DM

Atherosclerosis...one of the previous seminars...