Diabetes Mellitus - Information Overview

Diabetes mellitus is a syndrome of chronic hyperglycemia that develops as a result of genetic and exogenous factors. The disease is caused by impaired insulin secretion and varying degrees of peripheral insulin resistance, leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia, polyphagia, and polyuria.

Further complications include angiopathy, peripheral neuropathy, and susceptibility to infection. Diagnosis is based on glucose levels. Treatment includes diet, exercise, and glucose-lowering medications, including insulin and oral antihyperglycemic agents. Prognosis varies, depending on the degree of glucose control.

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Epidemiology

The prevalence of the disease among the population of various countries and ethnic groups is 1-3%. The incidence of diabetes in children and adolescents ranges from 0.1 to 0.3%. Taking into account undiagnosed forms, its prevalence in some countries reaches more than 6%.

Currently, more than 120 million people worldwide have diabetes. Every year, the number of newly diagnosed cases is 6-10% of the total number of patients, which leads to its doubling every 10-15 years. In economically developed countries, diabetes has become not only a medical but also a social problem.

The incidence of the disease largely depends on age. The number of patients with diabetes under 15 years of age is 5% of the entire population of patients with diabetes. Patients over 40 years of age make up about 80%, and over 65 years of age - 40% of the entire contingent of patients.

The influence of gender has little effect on the frequency of juvenile diabetes, and with increasing age, a predominance of sick women is observed in European countries, the USA, and Africa. In Japan, India, and Malaysia, diabetes mellitus occurs somewhat more often in men, and in Mexico and among American Indians, it is equally common in both sexes. Obesity, hyperlipidemia, hyperinsulinemia, and arterial hypertension have a significant effect on the prevalence of diabetes in adults. The combination of several risk factors significantly (28.9 times) increases the likelihood of developing clinical diabetes.

National and geographic factors also influence the prevalence of the disease. Thus, in some countries of Southeast Asia, Oceania, North Africa, and among the Eskimos, diabetes is much less common than among the population of Europe and the USA.

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Causes diabetes mellitus

The first indications of the hereditary nature of diabetes date back to the 17th century. The first hypothesis about the hereditary nature of the disease was formulated by Wegeli (1896). However, intensive study of the hereditary nature of diabetes mellitus began only in the 20-30s of our century, and by the 60s it was proven that the main etiological factor of this disease is genetic. Evidence of its hereditary determinacy consisted in the prevalence of familial forms over the prevalence of diabetes mellitus in the population and the prevalence of concordance among monozygotic twins compared to dizygotic ones.

In 1974, J. Nerup et al., AG Gudworth and J. C. Woodrow discovered an association of the B-locus of leukocyte histocompatibility antigens with type I diabetes mellitus - insulin-dependent (IDD) and its absence in patients with non-insulin-dependent diabetes mellitus type II. The authors' data indicated that the prevalence of HLA antigen B8 was 49% in patients with type I diabetes and 31% in healthy individuals, and HLA B15 was 21% and 10%, respectively. Further studies confirmed these data and established the prevalence of other HLA antigens related to the D-, DR- and DQ-loci in patients with type I diabetes. Thus, in patients with IDD, H1A antigens - Dw3, DRw3, Dw4, DRw4 - were detected with a higher frequency compared to the control group of healthy individuals. The presence of haplotypes B8 or B15 in the examined individuals increased the risk of diabetes by 2-3 times, B8 and B15 simultaneously - approximately 10 times. The presence of haplotypes Dw3/DRw3 increased the relative risk by 3.7 times, Dw4/DRw4 - by 4.9, and Dw3/DRw4 - by 9.4 times.

Studies of monozygotic twins depending on the type of diabetes mellitus have shown that the frequency of concordance in type II diabetes is significantly higher (48 of 55) than among twins with type I (80 of 147). The results of subsequent observations indicate that the concordance of monozygotic twins with type II diabetes reaches 100% (with increasing age), and with type I - 10-50%. The percentage of concordance among twins with IDD is significantly higher than among dizygotic twins or sibs, which confirms the genetic genesis of the disease. However, a fairly high percentage of discordance is a strong argument in favor of other factors.

The results of the study revealed genetic heterogeneity of diabetes mellitus and a marker of type 1 diabetes. However, the issue of the genetic marker (HLA antigens) cannot yet be considered fully resolved, since it should be detected in 90-100% of patients predisposed to diabetes and absent in healthy individuals. The difficulties in interpreting "diabetogenic" HLA phenotypes lie in the fact that, along with HLA antigens of loci B and D, often found in type 1 diabetes, HLA antigens were found that have a protective effect, preventing the development of diabetes. Thus, HLA B7 was detected in only 13% of patients with type 1 diabetes, and in 27% of healthy individuals. The relative risk of developing diabetes in HLA B7 carriers was 14.5 times lower compared to individuals who do not have HLA B7. Other HLA antigens also have a protective effect - A3, DW2 and DRw2. Ongoing studies of the relationship between HLA antigens and diabetes mellitus have shown that HLA A2, B18 and Cw3 are found more frequently in patients with type I diabetes than in the general population.

All of the above creates great difficulties in predicting the relative risk of diabetes mellitus development in various variants of the HLA phenotype, including both diabetogenic and protective variants of HLA antigen loci. Leukocyte histocompatibility antigens determine the individual immunological response of the body to various antigens and are not directly related to carbohydrate metabolism.

The HLA antigen profile in each individual is controlled by a complex of genes located on the short arm of chromosome 6, as well as a rare type of properdin (BfF-1), found in 23% of patients with type 1 diabetes, compared with 2% in the general population. The HLA phenotype in diabetes is thought to be a genetic determinant of the sensitivity of pancreatic beta cells to viral or other antigens and reflects the nature of the body's immunological response.

In the process of studying the features of HLA phenotypes in patients with type I diabetes, its genetic heterogeneity was discovered. Thus, in HLA B8 carriers, a connection with Dw3 was often revealed, which correlated with concordance in monozygotic twins. It was characterized by "the absence of antibodies to exogenous insulin, an increase in the frequency of microangiopathies, a combination with other autoimmune diseases, the presence of antibodies to pancreatic islet cells and a reduced frequency of occurrence of the B7 antigen. HLA B15 is often combined with Cw3. At the same time, the presence of antibodies to exogenous insulin, the usual frequency of microangiopathies, the absence of concomitant autoimmune diseases, the normal frequency of occurrence of HLA B7 and the detection of antigens in both concordant and discordant monozygotic twins for diabetes are noted.

The main factors that provoke the development of type I diabetes in cases of genetic predisposition to it are viral infections.

Type II diabetes mellitus is also based on genetic predisposition, which is confirmed by 100% concordance of monozygotic twins. However, its genetic marker has not yet been discovered, although there is data on the localization of type II diabetes genes in chromosome 11. The main provoking factor in this case is obesity.

The nature of inheritance of diabetes mellitus types I and II is not entirely clear. The issue of polygenic inheritance is discussed, where genetic factors (polygeny) and exogenous (exogeny) are interconnected and participate in the manifestation of the disease. Certain environmental factors (disease implementers) must join the genetic ones so that polygenically determined traits or predisposition to the disease are realized.

More definite conclusions about the inheritance pathways of diabetes mellitus type I can be made after studying the nature of HLA phenotypes in relatives of probands (in a large number of pedigrees). Taking into account the available data obtained on the basis of identifying clinical forms of diabetes, it is possible to conclude about the recessive inheritance pathway through a generation in the presence of two or more mutant genes with incomplete penetrance.

The results of systematic family examinations are in the best agreement with the multifactorial determinacy of type II diabetes mellitus. The values characterizing the frequency of the disease among the parents of probands and sibs are significantly lower than those expected for the recessive or dominant inheritance pathways. Type II diabetes is characterized by the detection of the disease from generation to generation, which is typical for the dominant inheritance pathway. However, the frequency of clinical and latent forms of the disease is significantly lower (even in children of two diabetic parents) than in the monogenic autosomal dominant inheritance pathway. This once again confirms the hypothesis of a multifactorial inheritance system. Genetic heterogeneity of diabetes has been found in animals with spontaneous diabetes. Thus, several types of impaired glucose tolerance with different modes of inheritance have been described in house mice. Goldstein and Motulsky (1975) propose a table of the actual risk of developing the disease, calculated on the basis of statistical processing on a computer of various literary sources containing information on the frequency of occurrence of diabetes in relatives of diabetic probands.

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Absolute risk for developing clinical diabetes

Subjects	Relatives with diabetes				Absolute risk, %
	Parents		Siblings
	One	Both	One	More than one
Child	+	-	-	-	5
»	-	+	-	-	10-15
»	+	-	+	-	10
Sibs	-	-	+	-	5
»	»	»	»	»	20
»	-	-	-	+	10

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Risk factors

Type 1 diabetes mellitus correlates with various viral diseases, seasonal factors and partly age, since the peak incidence in children occurs at 10-12 years of age.

A common risk factor, especially when type II diabetes is inherited, is the genetic factor.

There is evidence that excessive intake of cyanide from food (in the form of cassava), as well as a lack of protein in it, can contribute to the development of a special type of diabetes in tropical countries.

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Pathogenesis

Impaired glucose regulation (impaired glucose tolerance or impaired fasting glucose) is an intermediate, possibly transient, condition between normal glucose metabolism and diabetes mellitus that often develops with age, is a significant risk factor for diabetes mellitus, and may be present many years before the onset of diabetes mellitus. It is also associated with an increased risk of cardiovascular disease, but typical diabetic microvascular complications usually do not develop.

By now, not only the genetic but also the pathophysiological heterogeneity of diabetes mellitus has been fully proven. According to the classification of the disease proposed by the WHO Expert Committee (1981), two main pathogenetic forms of the disease are distinguished: diabetes type I (insulin-dependent) and diabetes type II (insulin-independent). The pathophysiological, clinical and genetic differences between the specified types of diabetes are presented in Table 8.

Characteristics of Types I and II Diabetes Mellitus

Indicators	Type1	Type II
Age at which the disease occurs	Children, youth	Senior, middle
Familial forms of the disease	Not often	Often
The influence of seasonal factors on the detection of the disease	Autumn-winter period	No
Phenotype	Skinny	Obesity
Haplotypes (HLA)	B8, B15, Dw3, Dw4, DRw3, DRw4	No connection found
The onset of the disease	Fast	Slow
Symptoms of the disease	Heavy	Weak or absent
Urine	Sugar and acetone	Sugar
Ketoacidosis	Prone to	Resistant
Serum insulin (IRI)	Low or absent	Normal or elevated
Anti-islet cell antibodies	Present	None
Treatment (basic)	Insulin	Diet
Concordance of monozygotic twins, %	50	100

In addition to other signs, significant differences are also observed in the degree of concordance (mutual morbidity) of identical twins. Of course, the 50% concordance rate in monozygotic twins in groups of patients with type 1 diabetes mellitus is significantly higher than among dizygotic twins or sibs, which indicates that the genetic factor plays a significant role in the pathogenesis of the disease. Discordance in this group of twins, which is 50%, also indicates a large role of other factors (in addition to genetic ones), for example, viral diseases. It is assumed that the HLA system is a genetic determinant that determines the sensitivity of pancreatic beta cells to viral antigens, or reflects the degree of expression of antiviral immunity.

Thus, type 1 diabetes is caused by the presence of mutant diabetic genes in chromosome 6 related to the HLA system, which determines the individual, genetically determined response of the body to various antigens. Mutant genes are apparently associated with the HLAD segment. In addition to diabetogenic HLA haplotypes, protective leukocyte antigens have also been found, for example, HLA B7 and A3, DR2, which can prevent the development of diabetes, despite the presence of mutant genes. The risk of developing diabetes is significantly higher in patients with two HLA - B8 and B15, than in those with one of them.

Despite the fact that type I diabetes is characterized by association with HLA antigens and certain clinical and pathophysiological parameters, it is heterogeneous. Depending on the pathogenetic features, type I diabetes is divided into two subtypes: 1a and Ib. Subtype 1a is associated with a defect in antiviral immunity, so the pathogenetic factor is a viral infection that causes destruction of beta cells of the pancreatic islets. Smallpox viruses, Coxsackie B, and adenovirus are believed to have tropism for the islet tissue of the pancreas. Destruction of the islets after a viral infection is confirmed by specific changes in the pancreas in the form of "insulitis", expressed in infiltration by lymphocytes and plasma cells. When "viral" diabetes occurs, circulating autoantibodies to the islet tissue are found in the blood. As a rule, the antibodies disappear after 1-3 years.

Diabetes 1b accounts for 1-2% of all patients with diabetes. This subtype of diabetes is considered as a manifestation of an autoimmune disease, which is confirmed by the frequent combination of diabetes type 1b with other autoimmune endocrine and non-endocrine diseases: primary chronic hypocorticism, hypogonadism, autoimmune thyroiditis, toxic goiter, hypoparathyroidism, vitiligo, pernicious anemia, alopecia areata, rheumatoid arthritis. In addition, autoantibodies circulating in the islet tissue are detected before clinical diabetes is detected and are present in the blood of patients during almost the entire period of the disease. The pathogenesis of type 1b diabetes is associated with a partial genetically determined defect in the immune surveillance system, i.e. with the inferiority of suppressor T-lymphocytes, which normally prevent the development of phorbid clones of T-lymphocytes directed against the tissue proteins of the body itself.

The differences between 1a- and 1b _- subtypes of diabetes are confirmed by the prevalence of HLA B15, DR4 in 1a-subtype and HLA B8, DR3 in 1b-subtype. Thus, subtype 1a of diabetes is caused by a violation of the body's immune response to some exogenous antigens (viral), and subtype Ib is an organ-specific autoimmune disease.

Type II diabetes (insulin-independent) is characterized by a high concentration of familial forms of the disease, significant influence on its manifestation of environmental factors, the main one being obesity. Since this type of diabetes is combined with hyperinsulinemia, the patients have predominantly lipogenesis processes that contribute to obesity. Thus, on the one hand, it is a risk factor, and on the other - one of the early manifestations of diabetes. The insulin-independent type of diabetes is also pathogenetically heterogeneous. For example, the clinical syndrome of chronic hyperglycemia, hyperinsulinemia and obesity can be observed with excessive secretion of cortisol ( Itsenko-Cushing's disease ), growth hormone (acromegaly), glucagon (glucagonoma), excess production of antibodies to endogenous insulin, with some types of hyperlipidemia, etc. Clinical manifestations of type II diabetes are expressed in chronic hyperglycemia, which responds well to treatment with a diet that promotes weight loss. Usually, ketoacidosis and diabetic coma are not observed in patients. Since type II diabetes occurs in people over 40 years old, the general condition of patients and their ability to work often depend on concomitant diseases: hypertension and complications of atherosclerosis, which occur in patients with diabetes several times more often than in the general population of the corresponding age group. The proportion of patients with type II diabetes is approximately 80-90%).

Some of the most severe manifestations of diabetes mellitus, regardless of its type, are diabetic microangiopathy and neuropathy. Metabolic disorders, mainly hyperglycemia, characteristic of diabetes mellitus, play a significant role in their pathogenesis. The determining processes developing in patients and underlying the pathogenesis of microangiopathy are glycosylation of body proteins, disruption of cellular function in insulin-independent tissues, changes in the rheological properties of blood and hemodynamics. In the 70s of our century, it was discovered that in patients with decompensated diabetes, the content of glucosylated hemoglobin increases compared to healthy people. Glucose, by a non-enzymatic process, reacts with the N-terminal amino group of the B-chain of the hemoglobin A molecule to form ketoamine. This complex is found in erythrocytes for 2-3 months (the lifespan of an erythrocyte) in the form of small fractions of hemoglobin A _1c or A _1abc. At present, the possibility of glucose addition with the formation of ketoamine and to the A-chain of the hemoglobin molecule has been proven. A similar process of increased glucose inclusion in blood serum proteins (with the formation of fructosamine), cell membranes, low-density lipoproteins, peripheral nerve proteins, collagen, elastin and lens has been found in most patients with diabetes mellitus and experimental diabetic animals. Changes in basement membrane proteins, their increased content in endothelial cells, aortic collagen and the basement membrane of the renal glomeruli can not only disrupt cell function, but also contribute to the formation of antibodies to altered vascular wall proteins (immune complexes), which can participate in the pathogenesis of diabetic microangiopathy.

In the pathogenesis of the disorder of the cellular function of insulin-independent tissues, increased stimulation (against the background of hyperglycemia) of the enzymatic polyol pathway of glucose metabolism plays a role. Glucose in proportion to its concentration in the blood enters the cells of insulin-independent tissues, where it, without being phosphorylated, is converted under the influence of the enzyme aldose reductase into a cyclic alcohol - sorbitol. The latter, with the help of another enzyme, sorbitol dehydrogenase, is converted into fructose, which is utilized without the participation of insulin. The formation of intracellular sorbitol occurs in the cells of the nervous system, pericytes of the retina, pancreas, kidneys, lens, and vascular walls containing aldose reductase. The accumulation of excess sorbitol in cells increases osmotic pressure, causing cellular edema, and creates conditions for dysfunction of cells of various organs and tissues, contributing to microcirculation disorders.

Hyperglycemia can disrupt metabolism in the nervous tissue in various ways: by decreasing sodium-dependent absorption of myoinositol and/or increasing the polyol pathway of glucose oxidation (the content of myoinositol in the nervous tissue decreases) or by disrupting phosphoinositide metabolism and sodium-potassium-ATPase activity. Due to the expansion of tubulin glycosylation, the microtubular function of axons and the transport of myoinositol, its intracellular binding, can be disrupted. These phenomena contribute to a decrease in nerve conduction, axonal transport, cellular water balance and cause structural changes in the nervous tissue. The clinical variability of diabetic neuropathy, independent of the severity and duration of diabetes, allows us to think about the possible influence of such pathogenetic factors as genetic and external (nerve compression, alcohol, etc.).

In the pathogenesis of diabetic microangiopathy, in addition to the previously mentioned factors, a role may also be played by a violation of hemostasis. In patients with diabetes mellitus, an increase in platelet aggregation is observed with an increase in the production of thromboxane A ₂, an increase in the metabolism of arachidonic acid in platelets and a decrease in their half-life, a violation of the synthesis of prostacyclin in endothelial cells, a decrease in fibrinolytic activity and an increase in the von Willebrand factor, which can contribute to the formation of microthrombi in vessels. In addition, an increase in blood viscosity, a slowdown in blood flow in the retinal capillaries, as well as tissue hypoxia and a decrease in the release of oxygen from hemoglobin A1, as evidenced by a decrease in 2,3-diphosphoglycerate in erythrocytes, may participate in the pathogenesis of the disease.

In addition to the above-mentioned iatogenetic factors, hemodynamic shifts in the form of microcirculation disorders may also play a role in the pathogenesis of diabetic microangiopathy and nephropathy. It is noted that in the initial stage of diabetes, capillary blood flow increases in many organs and tissues (kidney, retina, skin, muscle and adipose tissue). This, for example, is accompanied by an increase in glomerular filtration in the kidneys with an increase in the transglomerular pressure gradient. It was suggested that this process may cause protein entry through the capillary membrane, its accumulation in the mesangium with subsequent proliferation of the mesangium and lead to intercapillary glomerulosclerosis. Clinically, patients develop transient and then permanent proteinuria. The authors believe that this hypothesis is confirmed by the development of glomerulosclerosis in experimental diabetic animals after partial nephrectomy. T. N. Hostetter et al. proposed the following scheme of the sequence of development of kidney damage: hyperglycemia - increased renal blood flow - increased transglomerular hydrostatic pressure (with subsequent deposition of protein in the vascular wall and basement membrane) - protein filtration (albuminuria) - thickening of the mesangium - glomerulosclerosis - compensatory increase in filtration in the remaining glomeruli - renal failure.

Diabetic microangiopathy and histocompatibility antigens (HLA). In 20-40% of patients with 40-year duration of type 1 diabetes mellitus, diabetic retinopathy is absent, which allows us to assume a significant role in the development of microangiopathy not only metabolic disorders, but also a genetic factor. As a result of studying the association of HLA antigens and the presence or absence of diabetic proliferative retinopathy or nephropathy, conflicting data were obtained. Most studies did not note a relationship between neuropathy and the nature of the detected HLA antigens. Taking into account the detected heterogeneity of type 1 diabetes mellitus, it is believed that the HLA phenotype DR3-B8 is characterized by the predominance of constantly circulating antibodies to pancreatic islets, increased formation of circulating immune complexes, a weak immune response to heterologous insulin and mild manifestations of retinopathy. Another form of type 1 diabetes with the HLA B15-Cw3-DR4 phenotype is not associated with autoimmune diseases or persistent circulating antibodies to islet cells and occurs at an earlier age, often accompanied by proliferative retinopathy. An analysis of published studies that examined the possible association of HLA antigens with diabetic retinopathy in more than 1000 patients with type 1 diabetes showed that an increased risk of developing proliferative retinopathy is observed in patients with the HLA B15-DR4 phenotype, while the HLA B18 phenotype plays a protective role in relation to the risk of severe retinopathy. This is explained by a longer secretion of endogenous insulin (by C-peptide) in patients with HLA B18 and B7 phenotypes, as well as a frequent association with the Bf allele of properdin, which is localized in the short arm of chromosome 6 and may be related to retinopathy.

Pathological anatomy

Changes in the islet apparatus of the pancreas undergo a peculiar evolution depending on the duration of diabetes mellitus. As the duration of the disease increases, patients with type I diabetes experience a decrease in the number and degeneration of B cells with an unchanged or even increasing content of A and D cells. This process is a consequence of islet infiltration with lymphocytes, i.e. a process called insulitis and related to primary or secondary (against the background of viral infections) autoimmune damage to the pancreas. Insulin-deficiency diabetes is also characterized by diffuse fibrosis of the islet apparatus (in about 25% of cases), especially often in the combination of diabetes with other autoimmune diseases. In most cases, type I diabetes mellitus is characterized by islet hyalinosis and the accumulation of hyaline masses between cells and around blood vessels. In the early stages of the disease, foci of B-cell regeneration are observed, which completely disappear with increasing duration of the disease. In a significant number of cases, residual insulin secretion is observed, due to partial preservation of B-cells. Type II diabetes is characterized by a slight decrease in the number of B-cells. In the microcirculation vessels, thickening of the basement membrane is detected due to the accumulation of PAS-positive material, represented by glycoproteins.

The retinal vessels undergo various changes depending on the stage of retinopathy: from the appearance of microaneurysms, microthromboses, hemorrhages and the occurrence of yellow exudates to the formation of new vessels (neovascularization), fibrosis and retinal detachment after hemorrhage into the vitreous body with subsequent formation of fibrous tissue.

In diabetic peripheral neuropathy, segmental demyelination, degeneration of axons and connecting nerves are observed. Large vacuoles, giant neurons with degeneration, and swelling of dendrites are found in the sympathetic ganglia. In the sympathetic and parasympathetic neurons, thickening, fragmentation, and hyperargentophilia are observed.

The most characteristic of diabetes mellitus is diabetic nephropathy - nodular glomerulosclerosis and tubular nephrosis. Other diseases, such as diffuse and exudative glomerulosclerosis, arteriosclerosis, pyelonephritis and necrotic papillitis, are not specific to diabetes mellitus, but are combined with it much more often than with other diseases.

Nodular glomerulosclerosis (intercapillary glomerulosclerosis, Kimmelstiel-Wilson syndrome) is characterized by accumulation of PAS-positive material in the mesangium in the form of nodules along the periphery of the branches of glomerular capillary loops and thickening of the capillary basement membrane. This type of glomerulosclerosis is specific to diabetes mellitus and correlates with its duration. Diffuse glomerulosclerosis is characterized by thickening of the capillary basement membrane of all parts of the glomeruli, a decrease in the lumen of the capillaries and their occlusion. It is believed that diffuse glomerulosclerosis may precede nodular. Examination of kidney biopsies in patients with diabetes mellitus, as a rule, allows us to detect a combination of changes characteristic of both nodular and diffuse lesions.

Exudative glomerulosclerosis is expressed by the accumulation of homogeneous eosinophilic material resembling fibrinoid between the endothelium and the basement membrane of Bowman's capsule in the form of lipohyaline calyces. This material contains triglycerides, cholesterol, and PAS-positive polysaccharides.

Typical for tubular nephrosis is the accumulation of glycogen-containing vacuoles in epithelial cells, mainly in the proximal tubules, and the deposition of PAS-positive material in their cytoplasmic membranes. The degree of expression of these changes correlates with hyperglycemia and does not correspond to the nature of the tubular dysfunction.

Nephrosclerosis is the result of atherosclerotic and arteriolosclerotic lesions of small arteries and arterioles of the kidneys and is detected, according to autopsy data, in 55-80% of cases against the background of diabetes mellitus. Hyalinosis is observed in the efferent and afferent arterioles of the juxtaglomerular apparatus. The nature of the pathological process does not differ from the corresponding changes in other organs.

Necrotic papillitis is a relatively rare acute form of pyelonephritis characterized by ischemic necrosis of the renal papillae and venous thrombosis against the background of a rapidly progressing infection. Patients develop fever, hematuria, renal colic, and transient azotemia. Remnants of renal papillae are often found in the urine due to their destruction. Necrotic papillitis develops significantly more often in patients with diabetes mellitus.

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Symptoms diabetes mellitus

The most common symptoms of diabetes mellitus are: osmotic diuresis caused by glucosuria, leading to frequent urination, polyuria, polydipsia, which can progress to the development of orthostatic hypotension and dehydration. Severe dehydration causes weakness, fatigue, and changes in mental status. Diabetes mellitus has symptoms that can appear and disappear with fluctuations in glucose levels. Polyphagia may accompany the symptoms of diabetes, but is usually not the main complaint of patients. Hyperglycemia can also cause weight loss, nausea, vomiting, visual impairment, and a predisposition to bacterial or fungal infections.

Type 1 diabetes mellitus typically presents with symptomatic hyperglycemia and sometimes diabetic ketoacidosis. Some patients experience a prolonged but transient phase of near-normal glucose levels (the "honeymoon period") following the acute onset of the disease due to partial restoration of insulin secretion.

Type 2 diabetes mellitus may present with symptomatic hyperglycemia, but more often the disease is asymptomatic, with the condition being detected only during routine testing. Some patients present with initial symptoms of diabetic complications, suggesting a long history of the disease before diagnosis. Some patients initially develop hyperosmolar coma, particularly during times of stress or with further impairment of glucose metabolism caused by medications such as glucocorticoids.

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Forms

Classification of diabetes mellitus and other categories of impaired glucose tolerance

A. Clinical classes

1. Diabetes mellitus:
   1. insulin dependent - type I;
   2. insulin-independent - type II:
      • in individuals with normal body weight;
      • with obesity.
2. Other types, including diabetes mellitus associated with certain conditions or syndromes:
   • pancreatic diseases;
   • diseases of hormonal etiology;
   • conditions caused by drugs or chemicals;
   • changes in insulin receptors;
   • certain genetic syndromes;
   • mixed states.
3. Malnutrition Diabetes (Tropical):
   • pancreatic;
   • pancreatogenic.
4. Impaired glucose tolerance (IGT):
   • in individuals with normal body weight;
   • with obesity;
   • impaired glucose tolerance due to other specific conditions and syndromes.
5. Gestational diabetes.

B. Credible risk classes (individuals with normal glucose tolerance but with a significantly increased risk of developing diabetes)

1. previous history of impaired glucose tolerance;
2. potential impairment of glucose tolerance.

In turn, this type of diabetes is divided into two subtypes: pancreatic and pancreatogenic. The pathogenesis of tropical variants of the disease differs significantly from all other types. It is based on nutritional deficiency in childhood.

Pancreatic diabetes is further subdivided into fibrocalculous and protein-deficient. The former is common in India and Indonesia, primarily among men (3:1) and is characterized by the absence of ketosis in the presence of type I diabetes. Calcifications and diffuse fibrosis of the gland without inflammation are found in the pancreatic ducts of patients. This type of disease is characterized by low secretion of insulin and glucagon and malabsorption syndrome. The course of diabetes is often complicated by severe peripheral somatic polyneuropathy. Disease compensation is achieved by insulin administration. The pathogenesis of this form is associated with excessive consumption of foods containing cyanides (cassava, sorghum, millet, beans) against the background of a deficiency of protein foods. The second variant of pancreatic diabetes is called protein-deficient (Jamaican). It is caused by a low protein and saturated fat diet, occurs between the ages of 20 and 35, and is characterized by absolute insulin deficiency, insulin resistance (insulin requirement is 2 U/kg), and lack of ketosis.

Pancreatogenic diabetes is caused by excess iron intake and its deposition in the pancreas, such as during treatment for thalassemia (frequent blood transfusions), drinking alcohol stored in iron containers (common among the Bantu people of South Africa), and other factors causing secondary haemachromatosis.

Summarizing the above, it should be emphasized once again that diabetes mellitus (by analogy with hypertension ) is a syndrome that is genetically, pathophysiologically and clinically heterogeneous. This fact requires a differential approach not only in the study of pathogenesis, but also in the analysis of clinical manifestations, the choice of treatment methods, the assessment of the ability of patients to work and the prevention of various types of diabetes.

There are 2 main types of diabetes mellitus (DM) - type 1 and type 2, which differ in a number of features. The characteristics of the age of onset of DM (juvenile or adult diabetes mellitus) and the type of treatment (insulin-dependent or insulin-independent diabetes mellitus) are not adequate, which is due to the overlap of age groups and treatment methods for both types of the disease.

Type 1 diabetes

Type 1 diabetes mellitus (previously called juvenile or insulin-dependent diabetes) is characterized by the absence of insulin production due to autoimmune destruction of pancreatic cells, probably caused by environmental factors against the background of a genetic predisposition. Type 1 diabetes mellitus most often develops in childhood or adolescence and until recently was the most common form diagnosed before age 30; however, it can also develop in adults (latent autoimmune diabetes of adults). Type 1 diabetes mellitus accounts for less than 10% of all cases of diabetes.

The pathogenesis of autoimmune destruction of pancreatic cells involves poorly understood interactions between predisposing genes, autoantigens, and environmental factors. Predisposing genes include genes belonging to the major histocompatibility complex (MHC), especially HLADR3, DQB1*0201 and HLADR4, DQB 1*0302, which are present in more than 90% of patients with type 1 diabetes. Predisposition genes are more common in some populations than in others, which explains the prevalence of type 1 diabetes in some ethnic groups (Scandinavians, Sardinians).

Autoantigens include glutamic acid decarboxylase and other cellular proteins. These proteins are thought to be released during normal cell turnover or when cells are damaged (e.g., by infection), activating an immune response via mediator cells, leading to cell destruction (insulitis). Glucagon-secreting alpha cells remain undamaged. Antibodies to autoantigens that are detected in the blood are probably a response to (not a cause of) cell destruction.

Several viruses (including Coxsackievirus, rubella, cytomegalovirus, Epstein-Barr, retroviruses) have been associated with the onset of type 1 diabetes mellitus. Viruses can directly infect and destroy cells, and they can also cause indirect cell destruction by unmasking autoantigens, activating autoreactive lymphocytes, mimicking molecular sequences of autoantigens that stimulate the immune response (molecular mimicry), or other mechanisms.

Diet may also be a factor. Infant feeding of dairy products (especially cow's milk and the milk protein casein), high nitrate levels in drinking water, and inadequate vitamin D intake have been associated with an increased risk of developing type 1 diabetes. Early (< 4 months) or late (> 7 months) exposure to plant protein and grains increases islet cell antibody production. The mechanisms by which these processes occur are not understood.

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Classification of type I diabetes mellitus

Criteria	Characteristic
Clinical manifestations	Juvenile type, occurs mainly in children and adolescents; insulin-dependent
Etiological factors	Association with the HLA system, impaired immune response to viruses with tropism for beta cells
Pathogenesis	Beta cell destruction, lack of regeneration
	Type 1a	Type lb
Cause	Viruses	Impaired organ-specific immunity
Overall prevalence of diabetes, %	10	1
Insulin dependence	Available	Available
Floor	The ratio is equal	Women predominate
Age	Up to 30 years old	Any
Combination with autoimmune diseases	Not available	Frequent
Frequency of detection of antibodies to islet tissue	At the onset - 85%, after 1 year - 20%, as the duration of the disease increases - a tendency to disappear	At occurrence - unknown, after 1 year - 38%, antibody titer is constant
Antibody titer	1/250	1/250
Time of first detection of islet antibodies	Viral infection	Several years before diabetes developed

A clinical form of type II diabetes caused by the formation of autoantibodies to insulin receptors in the body (diabetes combined with acanthosis or lupus erythematosus) has been described. However, the pathogenesis of essential type II diabetes is still unclear. It was assumed that there was a pathology of insulin-dependent tissue receptors, which could explain the decrease in the biological effect of insulin with normal or increased levels in the blood. However, as a result of a detailed study of this problem in the 1970s, it was revealed that there were no significant quantitative changes in tissue receptors or transformations in the processes of their binding to insulin in patients with diabetes. At present, it is believed that the insufficient sugar-lowering effect of biologically active endogenous insulin in type II diabetes is apparently due to a genetic defect in the post-receptor apparatus of insulin-dependent tissues.

In 1985, on the recommendation of the WHO, in addition to the previously identified types of diabetes, another clinical form was included in the classification. It is caused by malnutrition, mainly in tropical countries in patients aged 10-50 years.

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Type 2 diabetes

Type 2 diabetes mellitus (previously called adult-onset or non-insulin-dependent diabetes) is characterized by insulin secretion that does not meet the needs of the patient. Insulin levels are often very high, especially early in the disease, but peripheral insulin resistance and increased hepatic glucose production make it insufficient to normalize glucose levels. The disease usually develops in adults and its incidence increases with age. Post-meal glucose levels are higher in older individuals than in younger individuals, especially after high-carbohydrate meals, and it takes longer for glucose levels to return to normal, partly because of increased accumulation of visceral/abdominal fat and decreased muscle mass.

Type 2 diabetes is increasingly observed in childhood due to the epidemic growth of childhood obesity: 40 to 50% of cases of newly diagnosed diabetes in children are now type 2. More than 90% of adult patients with diabetes have type 2 of the disease. There are clear genetic determinants, as evidenced by the widespread prevalence of the disease in ethnic groups (especially American Indians, Hispanics, Asians) and in relatives of patients with diabetes. No genes have been identified that are responsible for the development of the most common forms of type 2 diabetes.

The pathogenesis is complex and not fully understood. Hyperglycemia develops when insulin secretion can no longer compensate for insulin resistance. Although insulin resistance is characteristic of patients with type 2 diabetes, there is also evidence of cellular dysfunction, including impaired phase 1 secretion in response to intravenous glucose stimulation, increased proinsulin secretion, and accumulation of islet amyloid polypeptide. In the presence of insulin resistance, such changes typically develop over years.

Obesity and weight gain are important determinants of insulin resistance in type 2 diabetes mellitus. They have some genetic predisposition, but also reflect diet, exercise, and lifestyle. Adipose tissue increases free fatty acid levels, which may impair insulin-stimulated glucose transport and muscle glycogen synthase activity. Adipose tissue also functions as an endocrine organ, producing numerous factors (adipocytokines) that have beneficial (adiponectin) and unfavorable (tumor necrosis factor-a, IL6, leptin, resistin) effects on glucose metabolism.

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Diagnostics diabetes mellitus

Diabetes mellitus is indicated by typical symptoms and signs, and the diagnosis is confirmed by measuring glucose levels. The most effective measurements are after 8-12 hours of fasting [fasting glycemia (FG)] or 2 hours after taking a concentrated glucose solution [oral glucose tolerance test (OGTT)]. OTT is more sensitive for diagnosing diabetes mellitus and impaired glucose tolerance, but is also more expensive, less convenient, and less reproducible than OGTT. Therefore, it is less often used for routine purposes other than diagnosing gestational diabetes and for research.

In practice, diabetes mellitus or impaired fasting glucose are often diagnosed using random glucose or glycosylated hemoglobin (HbA1c) measurements. A random glucose level of more than 200 mg/dL (> 11.1 mmol/L) may be diagnostic, but the values may be affected by recent food intake, so repeat testing is necessary; repeat testing may not be necessary if symptoms of diabetes are present. HbA1c measurement reflects glucose levels over the previous 2-3 months. Values more than 6.5 mg/dL indicate abnormally high glucose levels. However, the assays and reference range are not standardized, so values may be falsely high or low. For these reasons, HbA1c is not yet considered as reliable as TBT or GL for diagnosing diabetes mellitus and should be used primarily for diabetes monitoring and control.

Urine glucose determination, a previously widely used method, is no longer used for diagnosis or monitoring because it is neither sensitive nor specific.

In those at high risk for type 1 diabetes (e.g., relatives or children of people with type 1 diabetes), testing for islet cell antibodies or glutamic acid decarboxylase antibodies, which precede the onset of clinical manifestations of the disease, may be performed. However, there are no proven preventive measures for the high-risk group, so such tests are usually used for research purposes.

Risk factors for type 2 diabetes mellitus include age greater than 45; overweight; sedentary lifestyle; family history of diabetes mellitus; history of impaired glucose regulation; gestational diabetes mellitus or birth of a child greater than 4.1 kg; history of hypertension or dyslipidemia; polycystic ovary syndrome; and black, Hispanic, or American Indian ethnicity. The risk of insulin resistance among overweight patients (body mass index 25 kg/m2) is increased by serum triglycerides 130 mg/dL (1.47 mmol/L); triglyceride/high-density lipoprotein ratio 3.0. Such patients should be screened for diabetes mellitus with fasting glucose levels at least every 3 years if normal and at least annually if impaired fasting glucose is detected.

All patients with type 1 diabetes should be screened for diabetic complications 5 years after diagnosis; for patients with type 2 diabetes, screening for complications begins at diagnosis. Patients' feet should be examined annually for abnormalities in pressure, vibration, pain, or temperature sense, which are consistent with peripheral neuropathy. Pressure sense is best assessed with a monofilament esthesiometer. The entire foot, and especially the skin under the metatarsal heads, should be examined for fissuring and signs of ischemia such as ulceration, gangrene, fungal nail infection, absent pulses, and hair loss. Ophthalmoscopic examination should be performed by an ophthalmologist; the interval for examinations is controversial but ranges from annually for patients with known retinopathy to every three years for patients without retinopathy on at least one examination. A urine smear or 24-hour urine test is indicated annually to detect proteinuria or microalbuminuria, and creatinine should be measured to assess renal function. Many consider electrocardiography to be important in cardiovascular risk assessment. Lipid profiles should be performed at least annually and more frequently if changes are detected.

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Treatment diabetes mellitus

Diabetes mellitus is treated based on glucose control to improve the patient's condition and prevent complications while minimizing hypoglycemic events. The goals of treatment are to maintain glucose levels of 80 to 120 mg/dL (4.4 to 6.7 mmol/L) during the day and 100 to 140 mg/dL (5.6 to 7.8 mmol/L when using home glucose monitoring) at night and to maintain HbA1c levels less than 7%. These goals may be modified for patients in whom strict glycemic control is inappropriate: the elderly, patients with a short life expectancy, patients who experience recurrent hypoglycemic episodes, especially those with hypoglycemia unawareness, and patients who cannot communicate hypoglycemic symptoms (eg, young children).

The key elements for all patients are education, dietary and exercise recommendations, and glucose monitoring. All patients with type 1 diabetes require insulin. Patients with type 2 diabetes with moderately elevated glucose levels should be treated with diet and exercise, followed by one oral hypoglycemic agent, a second oral agent if lifestyle modification is insufficient (combination therapy) if needed, and insulin if two or more agents fail to achieve recommended targets. Patients with type 2 diabetes with more significant glucose elevation are usually treated with lifestyle modification and oral hypoglycemic agents simultaneously. Patients with impaired glucose regulation should be counseled about the risk of developing diabetes and the importance of lifestyle modification to prevent diabetes. They should be monitored for the development of symptoms of diabetes or elevated glucose levels; optimal testing intervals have not been defined, but once or twice a year is reasonable.

Patient education about the causes of diabetes; diet therapy; physical activity; medications, self-monitoring with a glucometer; symptoms and signs of hypoglycemia, hyperglycemia, and diabetic complications is essential for optimizing treatment. Most patients with type 1 diabetes can be taught to calculate their own drug doses. Education should be supplemented at each doctor's visit and each hospitalization. Formal diabetes education programs, usually conducted by nurses trained in diabetology and nutritionists, are often very effective.

A tailored diet can help patients control glucose fluctuations and help patients with type 2 diabetes lose excess weight. In general, all patients with diabetes should eat a diet low in saturated fat and cholesterol, moderate in carbohydrates, and preferably high-fiber whole grains. Although protein and fat contribute to the caloric content of food (and thus cause weight gain or loss), only carbohydrates have a direct effect on glucose levels. A low-carbohydrate, high-fat diet improves glucose control in some patients, but its long-term safety is questionable. Patients with type 1 diabetes should use carbohydrate counting or the food equivalent substitution system to titrate their insulin dose. Counting the amount of carbohydrate in food is used to calculate the pre-meal insulin dose. In general, 1 unit of rapid-acting insulin is needed for every 15 g of carbohydrate in the meal. This approach requires detailed patient education and is most successful when supervised by a diabetes dietitian. Some experts recommend using the glycemic index to differentiate between slowly and rapidly digestible carbohydrates, although others believe the index has little benefit. Patients with type 2 diabetes should limit calories, eat regularly, increase fiber intake, and limit refined carbohydrates and saturated fats. Some experts also recommend limiting protein intake to less than 0.8 g/(kg/day) to prevent progression to early nephropathy. Dietitian consultations should complement the physician's care; the patient and the person preparing the food should be present.

Exercise should be characterized by a gradual increase in physical activity to the maximum level for the patient. Some experts believe that aerobic exercise is better than isometric exercise in reducing body weight and preventing the development of angiopathy, but resistance training can also improve glucose control, so all types of exercise are beneficial. Hypoglycemia during intense exercise may require carbohydrate intake during exercise, usually 5 to 15 g of sucrose or other simple sugars. Patients with known or suspected cardiovascular disease and diabetes mellitus are advised to undergo stress testing before starting exercise, and patients with diabetic complications such as neuropathy and retinopathy should reduce exercise levels.

Observation

Diabetes mellitus can be controlled by assessing glucose, HbA1c, and fructosamine levels. Self-monitoring of whole blood glucose using capillary blood from a finger, test strips, or a glucometer is the most important. Self-monitoring is used to adjust diet and to advise a therapist on adjusting doses and timing of medications. There are many different monitoring devices. Almost all of them require a test strip and a device for puncturing the skin and obtaining a sample; most come with control solutions that should be used periodically to confirm proper calibration. The choice of device usually depends on patient preference, parameters, and characteristics such as time to obtain a result (usually 5 to 30 s), display size (large displays are convenient for patients with poor vision), and the need for calibration. Glucometers that allow testing in less painful areas than the fingertips (palm, shoulder, abdomen, thigh) are also available. Newer devices can measure glucose transcutaneously, but their use is limited by skin irritation and misinterpretation; new technologies may soon make the results reliable.

Patients with poor glucose control, or when a new medication or dose of an existing medication is started, may be advised to self-monitor once (usually in the morning on an empty stomach) to 5 or more times daily, depending on the patient's needs and capabilities, and the complexity of the treatment regimen. For most patients with type 1 diabetes, testing at least 4 times daily is most effective.

HbA1c levels reflect glucose control over the previous 2-3 months and allow for monitoring between physician visits. HbA1c should be measured quarterly in patients with type 1 diabetes and at least annually in patients with type 2 diabetes whose glucose levels are reasonably stable (more often when control is questionable). Home testing kits are useful for patients who can strictly follow instructions. The control suggested by HbA1c values sometimes differs from the determined daily glucose values due to falsely elevated or normal values. False increases may occur with renal failure (urea interferes with the test), low red blood cell turnover (in iron, folate, B12 deficiency anemia), high doses of aspirin, and high blood alcohol concentrations. Falsely normal results are observed with increased red blood cell turnover, particularly in hemolytic anemias, hemoglobinopathies (eg, HbS, HbC) or during treatment of deficiency anemias.

Fructosamine, which is primarily glycosylated albumin but also other glycosylated proteins, reflects glucose control over the preceding 1–2 weeks. Fructosamine monitoring may be used in intensive treatment of diabetes mellitus and in patients with hemoglobin abnormalities or high red cell turnover (causing false HbA1c results), but is more commonly used in research settings.

Glucosuria monitoring is a relative indicator of hyperglycemia and can be used only when blood glucose control is impossible. Conversely, self-monitoring of urinary ketone bodies is recommended for patients with type 1 diabetes mellitus who experience symptoms of ketoacidosis such as nausea or vomiting, abdominal pain, fever, cold or flu-like symptoms, excessively prolonged hyperglycemia (250 to 300 mg/dL) during self-monitoring of glucose levels.

Prevention

There is no treatment to prevent diabetes mellitus and its progression. In some patients, azathioprine, glucocorticoids, cyclosporine can induce remission of type 1 diabetes mellitus, probably by suppressing autoimmune destruction of β cells. However, toxicity and the need for lifelong treatment limit their use. In some patients, short-term treatment with anti-POP monoclonal antibodies reduces insulin requirements for at least 1 year in recent-onset disease by suppressing the autoimmune T cell response.

Type 2 diabetes can be prevented by lifestyle changes. Weight loss of 7% of baseline body weight combined with moderate physical activity (e.g. walking 30 minutes a day) can reduce the risk of developing diabetes in people at high risk by more than 50%. Metformin also reduces the risk of diabetes in patients with impaired glucose regulation. Moderate alcohol consumption (5-6 drinks per week), treatment with ACE inhibitors, angiotensin II receptor blockers, statins, metformin and acarbose may also have a preventive effect, but require further study before recommending preventive use.

Diabetes mellitus and its risk of complications can be reduced by strict glucose control, namely HbA1c level < 7.0%, control of hypertension and lipid levels.

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Forecast

An expert opinion on the working capacity of patients with diabetes mellitus and a correct assessment of their clinical and work prognosis are based on a combination of medical, social and psychological factors, the combination of which determines the practice of medical and work examination. Medical factors include the type of diabetes, the degree of severity (the presence and nature of complications) and concomitant diseases; social factors include the patient's main profession, the nature and conditions of work, the ability to adhere to a diet, work experience, level of education, living conditions, bad habits; psychological factors include an attitude towards work, relationships at work, the attitude towards the patient in the family, the ability to independently find a job in accordance with the state of health, etc.

The formulation of the clinical expert diagnosis should reflect the main clinical manifestations of the disease. The following formulations can serve as an example.

• Diabetes mellitus type I (insulin-dependent), severe form, labile course; retinopathy stage II, nephropathy stage IV, neuropathy (moderate distal polyneuropathy).
• Moderate diabetes mellitus type II (non-insulin-dependent); stage I retinopathy, neuropathy (mild distal polyneuropathy).

The ability to work of patients with diabetes mellitus types I and II is affected by the severity of the disease, the type of hypoglycemic therapy, and dysfunctions of the visual organ, kidneys, and nervous system caused by microangiopathies.

Indications for referral to the VTEK

The following indications are considered sufficient for referral to the VTEK:

• severe form of diabetes mellitus, both insulin-dependent and insulin-independent, characterized by manifestations of microangiopathy with significant impairment of the functions of the visual organ, kidneys, nervous system, or labile course (frequent hypoglycemic conditions and ketoacidosis);
• the presence of negative factors at work (significant physical or neuropsychic stress; work associated with driving transport, at height, near a conveyor; contact with vascular poisons, vibration, noise);
• the impossibility of finding employment without reducing qualifications or reducing the volume of production activities.

Patients are referred to the VTEK after an inpatient examination in the therapeutic or specialized departments of hospitals, in the endocrinology offices of dispensaries, having with them a detailed extract from the medical history and completed form No. 88.

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Criteria for determining the state of working capacity

Disability group I is established for patients with severe diabetes mellitus in the presence of pronounced manifestations of microangiopathy with significant impairment of functions: retinopathy stage III (blindness in both eyes), neuropathy in the form of significantly pronounced movement disorders (sharp paresis), ataxia, sensory, vegetative disorders, as well as diabetic encephalopathy and organic changes in the psyche; nephropathy stage V, with a tendency to hypoglycemic, diabetic coma. Such patients require constant care.

Disability group II is defined for patients with severe diabetes mellitus, occurring with pronounced manifestations of microangiopathy and less pronounced functional disorders: retinopathy stage II, neuropathy in the form of pronounced movement disorders (pronounced paresis), ataxia, sensory disorders, as well as persistent organic changes in the psyche, nephropathy stage IV. Such patients do not require constant care. In some cases, group II is prescribed to patients with severe diabetes mellitus with moderate or even initial manifestations of microangiopathy in the visual organ (retinopathy 0, I, II stages), nervous system (in the form of moderately expressed motor, sensory, vegetative disorders), when the severe form is caused by a labile course (truly labile or a treatment defect - inadequate insulin dose) with chaotic alternation of hypo- and hyperglycemic comas or ketoacidosis, for the period of correction of insulin therapy and appropriate long-term observation.

Disability group III is defined for patients with moderate type I diabetes mellitus in the presence of moderate or even initial manifestations of microangiopathy in the visual organ (retinopathy stage I), nervous system (neuropathy in the form of moderately expressed motor sensory, vegetative disorders and organic changes in the psyche), kidneys (nephropathy stages I-III) even without their clinical manifestations, provided that there are contraindicated factors in the patient's work in the main profession (work related to driving transport, staying near moving mechanisms, with electrical appliances, etc.), and rational employment entails a decrease in qualifications or a significant decrease in the volume of production activity. At the same time, for young people, disability group III is established for the period of retraining, acquisition of a new profession; for persons refusing rehabilitation measures (over 46 years of age), disability group III is established with a recommendation for rational employment, transfer to another job.

In severe type I diabetes mellitus with a labile course without a tendency to frequent comas, persons engaged in intellectual work (doctor, engineer, accountant) who have a positive attitude towards work, with initial or even moderate manifestations of microangiopathy in the absence of contraindicated factors in their work, in some cases, a disability group III can be determined with a recommendation to reduce the amount of work and create conditions for the correct treatment regimen.

Patients with mild to moderate diabetes mellitus types I and II in the absence of functional disorders of any organs, systems and contraindicated factors in work are recognized as able-bodied. Some restrictions in work (exemption from night shifts, business trips, additional loads) can be provided by the VKK of medical and preventive institutions. The most common reasons for the discrepancy between the expert decisions of the VTEK and the consultative and expert opinions of the CIETIN are inaccurate diagnostics due to incomplete examination of patients in medical and preventive institutions; underestimation of pathomorphological and functional disorders; underestimation of the nature of the work performed and working conditions. The listed diagnostic and expert errors often lead to incorrect professional orientation of patients, to recommendations for contraindicated types and conditions of work.

In relation to young patients with diabetes mellitus, vocational guidance should be provided starting from school. Group III disabled persons have access to professions of mental work associated with moderate neuropsychic stress, as well as professions of physical labor with light or moderate stress.

Disabled persons of group I can perform work in specially created conditions (special workshops, special sections), at enterprises where they worked before becoming disabled, taking into account their professional skills, or at home.

The employment of patients with diabetes mellitus in accordance with the medical and physiological classification of work by severity should be carried out taking into account medical, social and psychological factors, as well as the ability of patients to adhere to a dietary regimen and take hypoglycemic drugs.

Modern diagnostics, adequate diabetes therapy, dispensary observation, rational employment maintain the ability of patients to work, prevent possible complications and contribute to the prevention of disability and the retention of personnel in production. It should be borne in mind that the range of available jobs for patients with type II diabetes is much wider than for patients with type I diabetes.

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