Diasoce2.ppt1 Symptoms of diabetes mellitus Basic –Thirst –Polyuria –Weight loss –Fatigue...
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Transcript of Diasoce2.ppt1 Symptoms of diabetes mellitus Basic –Thirst –Polyuria –Weight loss –Fatigue...
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diasoce2.ppt 1
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
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diasoce2.ppt 2
Symptoms of diabetes mellitus
NOTHING
Type 2 for long time (months, years)
Hypertension
Myocardial infarction, stroke with very bad prognosis
Microangiopathic complications (amputation)
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diasoce2.ppt 3
Symptoms of diabetes mellitus
NOTHING
Gestational diabetes mellitus
Screening!
Harmful both for baby and mother
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diasoce2.ppt 4
Symptoms of diabetes mellitus
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diasoce2.ppt 5
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
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diasoce2.ppt 6
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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diasoce2.ppt 7
Two types of diabetes
AGE
SEX
32
m
52
f
9
f
28
m
42
m
35
f
47
f
53
f
46
f
57
m
WEIGHT 46 56 25 41 54 79 69 75 85 83
G/ blood 23,9 21,2 22,5 14,9 17,7 16,2 21,2 17,3 17,3 12,9
G/ urine +++ +++ +++ +++ +++ +++ +++ +++ +++ +++
ketones +++ + +++ + ++ neg neg neg neg neg
insulin 0 0 0 0 0 0,26 0,29 0,02 0,24 0,20
Bornstein & Lawrence, 1951
??
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diasoce2.ppt 8
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 toleranceand impaired fasting glucoseare RISK FACTORS
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diasoce2.ppt 9
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?
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diasoce2.ppt 10
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
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diasoce2.ppt 11
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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diasoce2.ppt 12
Type 1 diabetes – geographic differences, Type 1 diabetes – geographic differences, hot spots and genetic backgroundhot spots and genetic background
Peak: 10-25 yearsIn any ageLast years – very low ageINCIDENCE = cases/100 000/y• Finnland: 41• USA 15• 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!
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diasoce2.ppt 13
Genes of MHC (HLA) system
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diasoce2.ppt 14
Groove for peptides on MHCglycoproteins
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diasoce2.ppt 15
Interaction between T lymphocyte, and antigen presenting cells
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diasoce2.ppt 16
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
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diasoce2.ppt 17
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 proteinThe role of other genesThe 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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diasoce2.ppt 18
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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diasoce2.ppt 19
Etiology of type 2 diabetes mellitusEtiology 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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diasoce2.ppt 20
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diasoce2.ppt 21
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diasoce2.ppt 22
GLUT4
IR
INSULIN
glucose
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diasoce2.ppt 23
GLUT4
IR
INSULIN
glucose
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diasoce2.ppt 24
„disorder of secretion and disturbance of function“
performance of B cells
burden - obesity
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diasoce2.ppt 25
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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diasoce2.ppt 26
Different performance
Different burden
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diasoce2.ppt 27
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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diasoce2.ppt 28
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diasoce2.ppt 29
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diasoce2.ppt 30
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diasoce2.ppt 31
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diasoce2.ppt 32
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diasoce2.ppt 33
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diasoce2.ppt 34
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diasoce2.ppt 35
TYPE 2 DIABETES IS THETYPE 2 DIABETES IS THETIP OF THE ICEBERGTIP OF THE ICEBERG
05
101520253055 % TYPE 2 DIABETES MELLITUS % TYPE 2 DIABETES MELLITUS
often undiagnosedoften undiagnosedusual diagnosed too late usual diagnosed too late microvascular complications presentmicrovascular complications presentatherosclerosis acceleratedatherosclerosis accelerated
12 % IMPAIRED GLUCOSE TOLERANCE12 % IMPAIRED GLUCOSE TOLERANCE**atherosclerosis acceleratedatherosclerosis accelerated
cca 25 % INSULIN HYPERSECRETIONcca 25 % INSULIN HYPERSECRETION(INSULIN RESISTANCE, (INSULIN RESISTANCE, METABOLIC METABOLIC SYNDROME)SYNDROME)
impaired sympathetic regulation ?impaired sympathetic regulation ?obesity, hypertension, impaired lipid statusobesity, hypertension, impaired lipid statusatherosclerosis acceleratedatherosclerosis accelerated
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diasoce2.ppt 36
TYPE 2 DIABETES IS THETYPE 2 DIABETES IS THETIP OF THE ICEBERGTIP OF THE ICEBERG
05
101520253055 % TYPE 2 DIABETES MELLITUS % TYPE 2 DIABETES MELLITUS
12 % IMPAIRED GLUCOSE TOLERANCE12 % IMPAIRED GLUCOSE TOLERANCE**cca 25 % INSULIN HYPERSECRETIONcca 25 % INSULIN HYPERSECRETION
WHY ???WHY ???NondiagnosedNondiagnosedLate diagnosedLate diagnosedObesityObesityAging of the whole populationAging of the whole population
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diasoce2.ppt 37
CVD & DM 2 PREVENTION, 2CVD & DM 2 PREVENTION, 211stst CENTURYCENTURY
NUTRITION energycomposition , micronutrients
SMOKING & ALCOHOL HUNTING & GATHERING (PHYSICAL ACTIVITY)HEALTH AWARENESS
weight control blood lipids, glucose blood pressure inherited and acquired health risks
55% S, 55% S, 30% F30% F, 15% P, 15% P