Causes and pathogenesis of diabetic neuropathy

Causes and pathogenesis of diabetic neuropathy

The pathogenesis of diabetic neuropathy is not fully understood. The main initial pathogenetic factor of diabetic neuropathy is chronic hyperglycemia, which ultimately leads to changes in the structure and function of nerve cells. Probably, the most important role is played by microangiopathy (changes in vasa nervorum with impaired blood supply to nerve fibers) and metabolic disorders, which include:

• activation of the polyol shunt (fructose metabolism disorder) - an alternative pathway of glucose metabolism, as a result of which it is converted into sorbitol under the action of aldose reductase, then into fructose, the accumulation of sorbitol and fructose leads to hyperosmolarity of the intercellular space and swelling of the nervous tissue;
• reduction of the synthesis of components of the membranes of nerve cells, leading to disruption of the conduction of nerve impulses. In this regard, the use of cyanocobalamin, which is involved in the synthesis of the myelin sheath of the nerve, reduces pain associated with damage to the peripheral nervous system, and stimulates nucleic acid metabolism through the activation of folic acid, seems to be effective in diabetic neuropathy;
• non-enzymatic and enzymatic glycosylation of structural proteins of the nerve column (myelin and tubulin), leading to demyelination and disruption of nerve impulse conduction; glycosylation of proteins of the capillary basement membrane causes its thickening and disruption of metabolic processes in nerve fibers. In this regard, the use of cyanocobalamin, which is involved in the synthesis of the myelin sheath of the nerve, reduces pain associated with damage to the peripheral nervous system, stimulating nucleic acid metabolism through the activation of folic acid, seems effective in diabetic neuropathy;
• increased oxidative stress and suppression of the antioxidant system with subsequent accumulation of free radicals (direct cytotoxic effect). To suppress this process, thioctic acid is used - a coenzyme in the oxidative decarboxylation of alpha-keto acids;
• autoimmune processes (according to some data, antibodies to insulin suppress the nerve growth factor, which leads to atrophy of nerve fibers).

Epidemiology of diabetic neuropathy

The frequency of various forms of neuropathy among patients with diabetes reaches 65-80%. Diabetic neuropathy develops at any age, but clinical manifestations are more common in people over 50 years of age. It affects patients with diabetes mellitus types 1 and 2 with almost equal frequency. The most common form of damage to the peripheral nervous system is diabetic diffuse peripheral polyneuropathy (about 80%). The second most common is autonomic diabetic neuropathy (found in 15% of patients with diabetes at the time of diagnosis and in 50% - 20 years after the onset of the disease). Most often, the autonomic innervation of the cardiovascular system is affected.

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Classification of diabetic neuropathy

Diffuse neuropathy includes:

Distal symmetrical neuropathy:

• with predominant damage to sensory nerves (sensory form of diabetic neuropathy);
• with predominant damage to the motor nerves (motor form of diabetic neuropathy), with combined damage to the sensory and motor nerves (sensorimotor form of diabetic neuropathy);

Autonomic neuropathy:

• Gastrointestinal tract: gastric atony, diabetic enteropathy (night and postprandial diarrhea),
• cardiovascular system: non-myocardial infarction, orthostatic hypotension, heart rhythm disturbances;
• bladder;
• reproductive system: erectile dysfunction, retrograde ejaculation;
• other organs and systems: impaired pupillary reflex, impaired sweating, absence of symptoms of hypoglycemia.

Focal neuropathy includes:

• cranial nerve neuropathy;
• mononeuropathy (upper or lower limbs);
• multiple mononeuropathy;
• polyradiculopathy,
• plexopathy;
• tunnel syndromes (in the strict sense, they are not neuropathies, since they are caused by compression of a possibly unchanged nerve).

The following stages of diabetic polyneuropathy are distinguished:

• stage 0 - no manifestations of neuropathy;
• stage 1 (subclinical) - changes in the peripheral nervous system, detected by special quantitative neurological tests, while there are no clinical manifestations of neuropathy;
• stage 2 - the stage of clinical manifestations, when, along with altered neurological tests, there are signs and symptoms of neuropathy;
• stage 3 - characterized by severe impairment of nerve function, leading to severe complications, including the development of diabetic foot syndrome

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