Download Definition of diabetes mellitus

Symptoms of diabetes mellitus
• Basic
–
–
–
–
Thirst
Polyuria
Weight loss
Fatigue
• If you do not begin
insulin therapy
immediately
–
–
–
–
–
–
–
• Other
–
–
–
–
Muscle cramps
Obstipation
Blurred vision
Fungal and bacterial
infections
nausea, vomitus
abdominal pain
dehydration
Kussmaul breathing
(deep, acetone smell)
ketones in blood,
urine, acidosis
COMA DIABETICUM
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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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Symptoms of diabetes mellitus
NOTHING
Gestational diabetes mellitus
Screening!
Harmful both for baby and mother
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Symptoms of diabetes mellitus
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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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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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Two types of diabetes
Bornstein & Lawrence, 1951
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
+++ +++
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?
?
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 ?
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impaired glucose tolerance
and impaired fasting glucose
are RISK FACTORS
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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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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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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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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
• 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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Genes of MHC (HLA) system
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Groove for peptides on MHC
glycoproteins
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Interaction between T lymphocyte, and
antigen presenting cells
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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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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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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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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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INSULIN
glucose
IR
GLUT4
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INSULIN
glucose
IR
GLUT4
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„disorder of secretion and disturbance of
function“
performance of B cells
burden - obesity
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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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Different burden
Different performance
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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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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
30
25
20
15
10
5
0
cca 25 % INSULIN HYPERSECRETION
(INSULIN RESISTANCE, METABOLIC
SYNDROME)
impaired sympathetic regulation ?
obesity, hypertension, impaired lipid status
atherosclerosis accelerated
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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
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30
25
20
15
10
5
0
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CVD & DM 2 PREVENTION, 21st
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
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55% S, 30% F, 15% P37