1. diasoce2.ppt1 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 –(deep, acetone smell) –ketones in blood, –urine, acidosis COMA DIABETICUM

2. diasoce2.ppt2 Symptoms of diabetes mellitus NOTHING Type 2 for long time (months, years) Hypertension Myocardial infarction, stroke with very bad prognosis Microangiopathic complications (amputation)

3. diasoce2.ppt3 Symptoms of diabetes mellitus NOTHING Gestational diabetes mellitus Screening! Harmful both for baby and mother

4. diasoce2.ppt4 Symptoms of diabetes mellitus

5. diasoce2.ppt5 Diagnostic criteria of DM Symptoms of DM and 1 abnormal blood glucose* value –fasting  7,0 mmol/l –2h after 75 g glucose or casual  11,1 No symptoms present –two abnormal BG values on 2 days (as above) Not a perfect algorhythm –Uncertainity of BG assays !!! *Only on laboratory analyzers, from venous plasma; uncertainity  0,5 mmol/l

6. diasoce2.ppt6 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.

7. diasoce2.ppt7 Two types of diabetes AGE SEX 32 m 52 f 9f9f 28 m 42 m 35 f 47 f 53 f 46 f 57 m WEIGHT46562541547969758583 G/ blood23,921,222,514,917,716,221,217,3 12,9 G/ urine+++ ketones++++ +++neg insulin000000,260,290,020,240,20 Bornstein & Lawrence, 1951 ????

8. diasoce2.ppt8 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

9. diasoce2.ppt9 Classification of diabetic syndromes  Type 1 diabetes mellitus (10 % ?)  Type 2 diabetes mellitus (90 %? )  Other types of diabetes mellitus (rare?, long list)  Gestational diabetes mellitus (temporary dg.) LADA = late autoimmune diabetes of adults Slow type 1, not very rare, transition between type 1 and 2? Type 1 and 2 are only endpoints of a scale?

10. diasoce2.ppt10 Classification of diabetic syndromes  Type 1 diabetes mellitus (10 % ?)  Type 2 diabetes mellitus (90 %? )  Other types of diabetes mellitus (rare?, long list)  Gestational diabetes mellitus (temporary dg.) MODY = maturity onset diabetes of the young Monogenic forms of diabetes (1 – 7, mostly AD heredity) Previously classified as T1DM OR T2DM Not very rare  1,5 – 2 % of patients Good lessons for genes of T2DM And also MITOCHODRIAL DIABETES TRANSIENT NEONATAL DIABETES

11. diasoce2.ppt11 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.

12. diasoce2.ppt12 Type 1 diabetes – geographic differences, hot spots and genetic background Peak: 10-25 years In any age Last years – very low age INCIDENCE = cases/100 000/y Finnland:41 USA15 Germany 7 Greece: 5 Mexico, Japan, Cuba < 5 Sardinia 32 (hot spot) HLA haplotypes and DM 1 DR3/DR3 5.0 DR4/DR4 6.8 DR3/DR4 14.3 DR3/X 0.7 DR4/X 1.0 X/X 0.04 95% of DM 1 patients posses DR3 or 4 but these haplotypes are common in population!

13. diasoce2.ppt13 Genes of MHC (HLA) system

14. diasoce2.ppt14 Groove for peptides on MHC glycoproteins

15. diasoce2.ppt15 Interaction between T lymphocyte, and antigen presenting cells

16. diasoce2.ppt16 Etiology of type 1 diabetes The genetic background is related to the immune system (HLA glycoproteins are parts of antigen presenting cells*)  (Susceptibility to autoimmune destruction of  cells) External trigger – viral infections, cow milk protein  (Islet cell antibodies, Insulin autoantibodies, antiGAD present already before the manifestation) Long process, when the number of cells is < 5-10 % acute manifestation of symptoms in some days – weeks  Without insulin death in coma

17. diasoce2.ppt17 Etiology of type 1 diabetes The genetic background is related to the immune system (HLA glycoproteins are parts of antigen presenting cells*)  (Susceptibility to autoimmune destruction of  cells) External trigger – viral infections, cow milk protein  The role of other genes  The actual constellation of immune system – nonderstructive or destructive insulitis  (Islet cell antibodies, Insulin autoantibodies, antiGAD present already before the manifestation) Long process, when the number of cells is < 5-10 % acute manifestation of symptoms in some days – weeks  Without insulin death in coma

18. diasoce2.ppt18 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.

19. diasoce2.ppt19 Etiology of type 2 diabetes mellitus Heterogenous group of patients (heterogenous disease !) Mostly obese adults, family background Long period without complains, no ketosis Often hypertension, CHD At the beginning hyperinsulinemic (insulin resistant), later the secretion of insulin decreases – T2DM is a progressive disease Diabetes is only the end of the story!

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22. diasoce2.ppt22 GLUT4 IR INSULIN glucose

23. diasoce2.ppt23 GLUT4 IR INSULIN glucose

24. diasoce2.ppt24 „disorder of secretion and disturbance of function“ performance of B cells burden - obesity

25. diasoce2.ppt25 Secretion disorder is the first Genes regulating the intrauterine development of Langerhans islets Lessons from an extreme rare condition transient neonatal diabetes Small babies and DM2

26. diasoce2.ppt26 Different performance Different burden

27. diasoce2.ppt27 Everything is more complicated Increase of BG – secretion of insulin No insulin (T1DM) Disturbed function of signal pathway (T2DM) But our diet does not contain glucose! ENTEROINSULAR AXIS! – INCRETINS Glucagon like protein I and its decreased activity in T2DM?

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35. diasoce2.ppt35 TYPE 2 DIABETES IS THE TIP OF THE ICEBERG 5 % TYPE 2 DIABETES MELLITUS often undiagnosed usual diagnosed too late  microvascular complications present atherosclerosis accelerated 12 % IMPAIRED GLUCOSE TOLERANCE* atherosclerosis accelerated cca 25 % INSULIN HYPERSECRETION (INSULIN RESISTANCE, METABOLIC SYNDROME) impaired sympathetic regulation ? obesity, hypertension, impaired lipid status atherosclerosis accelerated

36. diasoce2.ppt36 TYPE 2 DIABETES IS THE TIP OF THE ICEBERG 5 % TYPE 2 DIABETES MELLITUS 12 % IMPAIRED GLUCOSE TOLERANCE* cca 25 % INSULIN HYPERSECRETION WHY ??? Nondiagnosed Late diagnosed Obesity Aging of the whole population

37. diasoce2.ppt37 CVD & DM 2 PREVENTION, 21 st CENTURY  NUTRITION  energy  composition, micronutrients   SMOKING & ALCOHOL   HUNTING & GATHERING  (PHYSICAL ACTIVITY)  HEALTH AWARENESS   weight control  blood lipids, glucose  blood pressure  inherited and acquired health risks 55% S, 30% F, 15% P