Diabetes mellitus

Diabetes mellitus is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, metabolism resulting from defects of insulin secretion, insulin action, or a combination of both. There are two types of diabetes mellitus: insulin dependent diabetes mellitus (IDDM) called type I diabetes and non-insulin dependent diabetes mellitus (INDDM) called type 2 diabetes.

Etiological classification of glycemia disorders

Type 1 (β-cell destruction, usually leading to absolute insulin deficiency)

• Autoimmune

• Idiopatic

Type 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance)

Other specific type

- Genetic defects of β-cell function;

- Genetic defect in insulin action;

- Diseases of the exocrine pancreas: pancreatitis, trauma/pancreatectomy, neoplasia, cystic fibrosis.

Endocrinophaties: Cushing's syndrome, acromegaly, phaeochromocytoma, hyperthyroidism

Drug or chemical-induced: cortisone, anti-depressant drugs, beta-blockers, thiazide, infections: cytomegalovirus.

Uncommon forms of immune-mediated diabetes.

Other genetic syndromes sometimes associated with diabetes: Down's syndrome, Friederich's ataxia, Klinefelter`s syndrome, Wolfram's syndrome.

Gestational diabetes.

Classification according to clinical feature

Severity of diabetes:

- mild (I degree), - moderate (II degree),

• severe (III degree).

Compensation state:

• compensated,

• subcompensated,

• decompensated.

Complications:

- ketoacidotic coma, hyperosmolar coma, lactacidotic coma, hypoglycemic coma;

• microangiopathy - retinopary, nephropaty;

• macroangiopathy,

• neuropathy.

The type I diabetes, it is due to a lack of endogenous pancreatic insulin production, whereas in type 2 diabetes, the rising blood glucose results from a combination of genetic predisposition, unhealthy diet, physical inactivity, and increasing weight with a central distribution resulting in complex pathophysiological processes.

Etiology and pathogenesis of insulin dependent diabetes mellitus

The precise cause is still unknown in both main types of diabetes, nevertheless the etiology is considered as interaction of environmental factors with a genetic susceptibility. The pattern of these factors differs in IDDM and NIDDM.

Insulin dependent diabetes mellitus has polygenic genetic predisposition. Recently the role of genetic factor has finally proved as principal reason on development diabetes mellitus. Over 50 % of the heritability is contributed by the HLA class II genes which determines immune responsiveness and located in 6 chromosome being the marker of the predisposition to the autoimmune damage pancreatic islet insulin-secreting cells, witch becomes insulin-auto-antibodies. Selective destruction of beta cells occurs. In clinical expression of the disease an important role have environmental factors. Viral infections can induce diabetes by two pathogenic mechanisms: destruction of the pancreatic beta cells by direct cytolysis result from possessing tropism to the Langergans' islet (German measles, Coxsackie B4 virus, virus of hepatitis B, epidemic parotitis and cytomegalovirus); induction of an autoimmune destructive process results from infections.

In modern diabetology the following stage of pathogenesis are offered:

The I stage is genetic predisposition, by presence of certain antigens of`HLA-system, and also genes 10 and 11 chromosomes.

The II stage is initiation of autoimmune process in beta-cells under influencing of pancreotroping viruses, cytostaties and other unknown factors.

The III stage is the stage of active immune processes with formation of antibodies to beta-cells, to insulin and by development of autoimmune insulitis.

The IV stage is progressive declining of secretion of insulin, by the stimulated glucose (I phase of secretion of insulin).

The V stage is clinical overt diabetes. This stage develops, in case of destruction and death of 85 90 % beta-cells.

The VI stage is complete destruction of beta-cells, complete absence of secretion of insulin and C-peptide.

Type I diabetes characterized by deficiency of insulin due to destructive lesions of pancreatic beta-cells; usually progresses to the stage of absolute insulin deficiency. Typically, it occurs in young subjects with acute onset with typical symptoms of diabetes together with weight loss and propensity to ketosis, but type 1 diabetes may occur at any age, sometimes with slow progression. People, who have antibodies to pancreatic beta-cells such as glutamic-acid-decarboxylase (GAD), arc likely lo develop either typical acute-onset or slow-progressive insulin-dependent diabetes. Today antibodies to pancreatic β-cells are considered as a marker of type 1 diabetes, although such antibodies are not detectable in all patients.