Diabetes mellitus
Etiology and pathogenesis.
Diabetes mellitus (DM) is a syndrome of chronical hyperglycemia associated with
absolute (severe) or relative (mild) insulin deficiency, derangement of all kinds of
metabolism, development of micro- and macroangiopathy, neuropathy and
pathologic changes in different organs and tissues.
the incidence of DM In highly developed industrial countries is about 5-6%.
Therefore the risk of IHD and AMI increases in 2 times
Arterial hypertension – in three times
Kidney pathology – in 17 times
Extremities gangrene – in 20 times
Etiological classification of glycemic impairment (WHO, 1999)
I. DM type 1 (β-cells destruction)
II. DM type 2
III. Other specific types
a) β-cells genetic impairments
b) insulin action genetic impairment
c) pancreas exocrine mechanism diseases
d) endocrinopathy
e) DM cased with drugs and chemical agents
f) Infections
g) unusual forms of immune appropriated DM
h) other genetic syndromes, sometimes associated with DM
IV. Gestational DM.
DM type I Pathogenesis.
There exist 6 stages of DM type I development.
The first stage is called – genetic predisposition.
The following arguments prove genetic predisposition.
- DM type 1 risk development for relations of birth increases populative one
in 20 times;
- The sibs’ risk is 5-8%.
- Monozygotic twins’ concordance is less than 50%.
- 90% of patients deny that they have relatives suffering of DM type 1.
1
, - 95% of patients with DM have got an associating with HLA-A6.
Second stage is called autoimmune processes trigging (viruses, and other agents).
1. The viruses can influence on β-cells in different ways:
a) direct cytolytic action is caused by epidemic parothitis virus,
encephalomyelocarditis and Cocsaky viruses etc.
b) autoimmune process trigging (german measles, reovirus).
2. Chemical agents (alloxane, streptozotocyne, cyprogeptadine, salts of heavy
metals, nitrites and nitrates).
3. Stress.
4. Ultraviolet radiation.
Diet ingredients (gluten, soy-been, milk of caws, glucose, non-saturated fats,
antioxidants, tee, coffee.
Third stage is called autoimmune processes activation in β-cells (see fig.1).
β-CELLS DEATH MECHANISM
I. Necrosis.
ENVIRONMENTAL FACTORS INFLUENCE
(VIRUSES, DRUGS, NUTRITION)
β-cell with genetic
predisposition
Enhancing of free-radicals oxydation
Output of toxic free-radicals
Protein denaturation in β-cells (necrosis)
Input necrosis products by macrophages
(phagocytosis)
Output IL-1, γ-IF, FNT
Autoimmune processes activation
2
Etiology and pathogenesis.
Diabetes mellitus (DM) is a syndrome of chronical hyperglycemia associated with
absolute (severe) or relative (mild) insulin deficiency, derangement of all kinds of
metabolism, development of micro- and macroangiopathy, neuropathy and
pathologic changes in different organs and tissues.
the incidence of DM In highly developed industrial countries is about 5-6%.
Therefore the risk of IHD and AMI increases in 2 times
Arterial hypertension – in three times
Kidney pathology – in 17 times
Extremities gangrene – in 20 times
Etiological classification of glycemic impairment (WHO, 1999)
I. DM type 1 (β-cells destruction)
II. DM type 2
III. Other specific types
a) β-cells genetic impairments
b) insulin action genetic impairment
c) pancreas exocrine mechanism diseases
d) endocrinopathy
e) DM cased with drugs and chemical agents
f) Infections
g) unusual forms of immune appropriated DM
h) other genetic syndromes, sometimes associated with DM
IV. Gestational DM.
DM type I Pathogenesis.
There exist 6 stages of DM type I development.
The first stage is called – genetic predisposition.
The following arguments prove genetic predisposition.
- DM type 1 risk development for relations of birth increases populative one
in 20 times;
- The sibs’ risk is 5-8%.
- Monozygotic twins’ concordance is less than 50%.
- 90% of patients deny that they have relatives suffering of DM type 1.
1
, - 95% of patients with DM have got an associating with HLA-A6.
Second stage is called autoimmune processes trigging (viruses, and other agents).
1. The viruses can influence on β-cells in different ways:
a) direct cytolytic action is caused by epidemic parothitis virus,
encephalomyelocarditis and Cocsaky viruses etc.
b) autoimmune process trigging (german measles, reovirus).
2. Chemical agents (alloxane, streptozotocyne, cyprogeptadine, salts of heavy
metals, nitrites and nitrates).
3. Stress.
4. Ultraviolet radiation.
Diet ingredients (gluten, soy-been, milk of caws, glucose, non-saturated fats,
antioxidants, tee, coffee.
Third stage is called autoimmune processes activation in β-cells (see fig.1).
β-CELLS DEATH MECHANISM
I. Necrosis.
ENVIRONMENTAL FACTORS INFLUENCE
(VIRUSES, DRUGS, NUTRITION)
β-cell with genetic
predisposition
Enhancing of free-radicals oxydation
Output of toxic free-radicals
Protein denaturation in β-cells (necrosis)
Input necrosis products by macrophages
(phagocytosis)
Output IL-1, γ-IF, FNT
Autoimmune processes activation
2
