1. Diabetes mellitus II - III First and second type of diabetes mellitus
Lecture from pathological physiology
© Oliver Rácz,
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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.
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3. Type 1 diabetes – geographic differences, hot spots and genetic background
Peak: years
In any age
Last years – very low age
INCIDENCE
= cases/ /y
Finnland: 41
USA 15
Germany 7
Greece: 5
Mexico, Japan, Cuba < 5
Sardinia 32 (hot spot)
HLA haplotypes and DM 1
DR3/DR
DR4/DR
DR3/DR
DR3/X
DR4/X
X/X
95% of DM 1 patients posses
DR3 or 4 but these haplotypes are common in population!
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4. Genes of MHC (HLA) system
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5. Groove for peptides on MHC glycoproteins
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6. Interaction between T lymphocyte, and antigen presenting cells
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7. 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 b 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
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8. 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 b 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
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9. 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.
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10. 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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11.
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12.
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13. INSULIN
glucose IR
GLUT4
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14. the engine is breaking down, full throttle!
INSULIN
glucose
the engine is breaking down, full throttle! IR
GLUT4
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15. „disorder of secretion and disturbance of function“
performance of B cells
burden - obesity
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16. 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
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17. Different performance
Different burden
Different performance
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18. HETEROGENITY OF T2DM? HROZBA PRE ŠTUDENTOV: T2DMA, T2DMB......T2DMG
OR?
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19. COMPONENT ANALYSIS !
McCarthy 2017
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20.
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21.
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22. 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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23.
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24.
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25.
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26.
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27.
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28. TYPE 2 DIABETES IS THE TIP OF THE ICEBERG
5 % TYPE 2 DIABETES MELLITUS
often undiagnosed
usual diagnosed too late Þ
microvascular complications present
atherosclerosis accelerated
12 % IMPAIRED GLUCOSE TOLERANCE*
cca 25 % INSULIN HYPERSECRETION
(INSULIN RESISTANCE, METABOLIC SYNDROME)
impaired sympathetic regulation ?
obesity, hypertension, impaired lipid status
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29. TYPE 2 DIABETES IS THE TIP OF THE ICEBERG
8 % TYPE 2 DIABETES MELLITUS
15 % IMPAIRED GLUCOSE TOLERANCE*
cca 25 % INSULIN HYPERSECRETION
WHY ???
Nondiagnosed
Late diagnosed
Obesity
Aging of the whole population
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30. CVD & DM 2 PREVENTION, 21st CENTURY
NUTRITION
energy ß composition , micronutrients Ý
SMOKING & ALCOHOL ß
HUNTING & GATHERING Ý (PHYSICAL ACTIVITY)
HEALTH AWARENESS Ý
weight control
blood lipids, glucose
blood pressure
inherited and acquired health risks
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55% S, 30% F, 15% P