The causes and pathogenesis of diabetic neuropathy

The 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 a change in the structure and function of nerve cells. Probably, the most important role is played by microangiopathy (changes in vasa nervorum with disturbed blood supply of nerve fibers) and metabolic disorders, which include:

• Activation of the polyol shunt (impaired fructose metabolism) is an alternative way of glucose metabolism, as a result of which it is converted to sorbitol by aldose reductase, then into fructose, the accumulation of sorbitol and fructose leads to hyperosmolarity of the intercellular space and edema of the nerve tissue;
• a decrease in the synthesis of the components of nerve cell membranes, leading to a disruption of the nerve impulse. In this regard, effective in diabetic neuropathy is the use of cyanocobalamin involved in the synthesis of the myelin sheath of the nerve, which reduces pain sensations associated with damage to the peripheral nervous system that stimulates nucleic acid metabolism through the activation of folic acid;
• non-enzymatic and enzymatic glycosylation of structural proteins of the neural column (myelin and tubulin), leading to demyelination and disturbance of the nerve impulse; glycosylation of the proteins of the basement membrane of capillaries causes its thickening and disorder of metabolic processes in nerve fibers. In this regard, effective in diabetic neuropathy is the use of cyanocobalamin involved in the synthesis of the myelin sheath of the nerve, which reduces pain associated with damage to the peripheral nervous system that stimulates nucleic acid metabolism through the activation of folic acid;
• increased oxidative stress and suppression of the antioxidant system followed by the accumulation of free radicals (direct cytotoxic action). To suppress this process, tioctic acid, coenzyme, is used in the oxidative decarboxylation of alpha-keto acids;
• autoimmune processes (according to some data, antibodies to insulin depress 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 mellitus reaches 65-80%. Diabetic neuropathy develops at any age, but clinical manifestations are more common in people older than 50 years. Practically with the same frequency affects patients with type 1 and type 2 diabetes. The most common form of damage to the peripheral nervous system is diabetic diffuse peripheral polyneuropathy (about 80%). The second most frequent is autonomic diabetic neuropathy (found in 15% of patients with diabetes at the time of diagnosis and 50% in 20 years after the onset of the disease). Most often, vegetative innervation of the cardiovascular system suffers.

[1], [2], [3], [4], [5], [6], [7]

Classification of diabetic neuropathy

To diffuse neuropathy carry:

Distal symmetrical neuropathy:

• with a primary lesion of the sensory nerves (sensory form of diabetic neuropathy);
• with a predominant lesion of the motor nerves (motor form of diabetic neuropathy), with a combined lesion of the sensory and motor nerves (sensorimotor form of diabetic neuropathy);

Autonomic neuropathy:

• Gastrointestinal tract: atony of the stomach, diabetic enteropathy (night and postprandial diarrhea),
• cardiovascular system: no-myocardial infarction, orthostatic hypotension, heart rhythm disturbance;
• Bladder;
• reproductive system: erectile dysfunction, retrograde ejaculation;
• other organs and systems: impaired pupillary reflex, impaired sweating, no symptoms of hypoglycemia.

Focal neuropathy is:

• neuropathy of cranial nerves;
• mononeuropathy (upper or lower extremities);
• multiple mononeuropathy;
• polyradiculopathy,
• plexopathy;
• Tunnel syndromes (in the strict sense are not neuropathies, because they are caused by compression, perhaps, of an unchanged nerve).

Distinguish the following stages of diabetic polyneuropathy:

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

[8], [9], [10], [11], [12], [13],