Symptoms of Diabetes

Symptoms of diabetes mellitus are manifested in two ways. This is due to acute or chronic insulin deficiency, which in turn can be absolute or relative. An acute insulin deficiency causes a state of decompensation of carbohydrate and other metabolic species, accompanied by clinically significant hyperglycemia, glucosuria, polyuria, polydipsia, hyperphagic weight loss, ketoacidosis, up to diabetic coma. Chronic insulin deficiency against a background of subcompensated and periodically compensated diabetes mellitus is accompanied by clinical manifestations characterized as "late diabetic syndrome" (diabetic retino-, neuro- and nephropathy), which is based on diabetic microangiopathy and metabolic disorders typical of chronic course of the disease .

The mechanism of development of clinical manifestations of acute insulin insufficiency includes disorders of carbohydrate, protein and fat metabolism, which cause hyperglycemia, hyperamino- cidemia, hyperlipidemia and ketoacidosis. Deficiency of insulin stimulates gluconeogenesis and glycogenolysis, and also suppresses glycogenesis in the liver. Consuming carbohydrates (glucose) to a lesser extent than in healthy, metabolized in the liver and insulin-dependent tissues. Stimulation of glucagonogenesis by glucagon (with insulin deficiency) leads to the use of amino acids (alanine) for the synthesis of glucose in the liver. The source of amino acids is the tissue protein that undergoes disintegration. Since the alanine amino acid is used in the process of gluconeogenesis, the content of branched chain amino acids (valine, leucine, isoleucine) increases, the utilization of which by muscle tissue for protein synthesis also decreases. Thus, patients develop hyperglycemia and aminocidemia. The increased consumption of tissue protein and amino acids is accompanied by a negative nitrogen balance and is one of the reasons for weight loss of patients, and significant hyperglycemia is caused by glucosuria and polyuria (as a consequence of osmotic diuresis). Loss of fluid in the urine, which can reach 3-6 l / day, causes intracellular dehydration and polydipsia. When the intravascular volume decreases, blood pressure decreases and the hematocrit number increases. In conditions of insulin deficiency, the main energy substrates of muscle tissue are free fatty acids, which are formed in adipose tissue as a result of enhanced lipolysis - hydrolysis of triglycerides (TG). Its stimulation as a result of activation of hormone-sensitive lipase causes an increased intake of blood sugar and glycerin into the bloodstream and liver. The first, oxidized in the liver, serve as a source of ketone bodies (beta-oxymosilic and acetoacetic acids, acetone) that accumulate in the blood (partially utilized by muscles and CNS cells), promoting ketoacidosis, reducing pH and tissue hypoxia. Partially FFA in the liver is used for the synthesis of TG, which causes fatty liver infiltration, and also enter the blood, which explains the often observed in patients with hyperglyceridemia and increased FFA (hyperlipidemia).

Progression and growth of ketoacidosis increase tissue dehydration, hypovolemia, hemoconcentration with a tendency to develop a syndrome of disseminated intravascular coagulation, worsening of blood supply, hypoxia and edema of the cerebral cortex, to the development of diabetic coma. A sharp decrease in renal blood flow can cause necrosis of the renal tubules and irreversible anuria.

The features of diabetes mellitus, as well as its clinical manifestations, largely depend on its type.

Diabetes type I, as a rule, is manifested by severe clinical symptoms, reflecting the characteristic insulin deficiency in the body. The onset of the disease is characterized by significant metabolic disorders that cause clinical manifestations of decompensation of diabetes mellitus (polydipsia, polyuria, weight loss, ketoacidosis) developing within a few months or days. Often the disease is first manifested by diabetic coma or severe acidosis. After the treatment, including in most cases, insulin therapy, and diabetes compensation, there is an improvement in the course of the disease. Thus, even after a diabetic coma has passed, the daily need for insulin gradually decreases, sometimes until its complete elimination. An increase in glucose tolerance leading to the possibility of abolishing insulin therapy after the elimination of severe metabolic disorders characteristic of the initial period of the disease is observed in many patients. The literature describes quite frequent cases of temporary recovery of such patients. However, a few months later, and sometimes 2-3 years later, the disease resumed (especially against the background of a viral infection), and insulin therapy became necessary throughout life. This long-noted pattern in the foreign literature has been called the "honeymoon of a diabetic", when there is a remission of the disease and no need for insulin therapy. Its duration depends on two factors: the degree of damage to the beta cells of the pancreas and its ability to regenerate. Depending on the prevalence of one of these factors, the disease can immediately assume the nature of clinical diabetes or a remission will occur. The duration of remission is further influenced by external factors such as the frequency and severity of concomitant viral infections. We observed patients who had a duration of remission of 2-3 years on the background of the absence of viral and intercurrent infections. In this case, not only the glycemic profile, but also the glucose tolerance test (GTT) in patients did not present abnormalities. It should be noted that in a number of studies the cases of spontaneous remission of diabetes were regarded as a result of the therapeutic effect of sulfanilamide hypoglycemic drugs or biguanides, while other authors attributed this effect to diet therapy.

After the emergence of persistent clinical diabetes, the disease is characterized by a small need for insulin, which increases for 1 -2 years and remains stable. The clinical course in the future depends on the residual secretion of insulin, which within the limits of subnormal values of the C-peptide can vary significantly. With a very low residual secretion of endogenous insulin, a labile course of diabetes with a tendency to hypoglycemia and ketoacidosis is observed, due to the large dependence of metabolic processes on insulin administered, the nature of nutrition, stress and other situations. Higher residual secretion of insulin provides a more stable course of diabetes and a smaller need for exogenous insulin (in the absence of insulin resistance).

Sometimes type I diabetes mellitus is combined with autoimmune endocrine and non-endocrine diseases, which is one of the manifestations of autoimmune polyendocrine syndrome. Since autoimmune polyendocrine syndrome can include the defeat of the adrenal cortex, with a decrease in blood pressure, it is necessary to clarify their functional state for taking adequate measures.

As the duration of the disease increases (after 10-20 years), clinical manifestations of late diabetic syndrome appear in the form of retino- and nephropathy, which progress more slowly with good compensation for diabetes mellitus. The main cause of death is renal failure and is much less common - complications of atherosclerosis.

In terms of severity, type I diabetes is divided into medium and heavy forms. The average degree of severity is characterized by the need for replacement insulin therapy (regardless of dose) in uncomplicated diabetes mellitus or the presence of retinopathy stage I, stage II, stage I nephropathy, peripheral neuropathy without severe pain syndrome and trophic ulcers. To a severe degree, insulin-deficient diabetes, combined with retinopathy of stage II and III, or nephropathy of stage II and III, peripheral neuropathy with severe pain or trophic ulcers, neurodystrophic blindness, difficult to treat, encephalopathy, severe manifestations of vegetative neuropathy, a tendency to ketoacidosis, repeated comatose condition, labile course of the disease. If there are listed manifestations of microangiopathy, the need for insulin and the level of glycemia are not taken into account.

The clinical course of type II diabetes mellitus (insulin-independent) is characterized by its gradual onset, without manifestations of decompensation. Patients are more likely to consult a dermatologist, gynecologist, neuropathologist about fungal diseases, furunculosis, epidermophytosis, itching in the vagina, pain in the legs, periodontitis, visual impairment. When examining such patients, they detect diabetes mellitus. It is often the first time to diagnose diabetes during myocardial infarction or stroke. Sometimes the disease makes its debut with a hyperosmolar coma. Due to the inconspicuous start of the disease in most patients [it is very difficult to determine its duration. This probably explains the relatively rapid (in 5-8 years) appearance of clinical signs of retinopathy or detection of it even during the primary diagnosis of diabetes mellitus. The course of type II diabetes is stable, with no tendency to ketoacidosis and hypoglycemic conditions when using only a diet or in combination with sugar-lowering oral medications. Since this type of diabetes usually develops in patients older than 40 years, there is a frequent combination with atherosclerosis, which is prone to rapid progression due to the presence of risk factors in the form of hyperinsulinemia and hypertension. Complications of atherosclerosis are most often the cause of death in this category of patients with diabetes mellitus. Diabetic nephropathy develops much less frequently than in patients with type I diabetes.

Diabetes mellitus type II in severity divided into 3 forms: mild, moderate and severe. The mild form is characterized by the possibility of diabetes compensation only by diet. Probably its combination with stage I retinopathy, stage I nephropathy, transient neuropathy. For diabetes of medium severity, the disease is compensated with sugar-reducing oral preparations. Perhaps a combination with retinopathy I and II stages, nephropathy of the first stage, transient neuropathy. In severe form, the disease is compensated for by sugar reduction drugs or by periodic administration of insulin. At this stage, retinopathy of stage III, nephropathy of stage II and III, severe manifestations of peripheral or vegetative neuropathy, encephalopathy are noted. Sometimes a severe form of diabetes is diagnosed in patients compensated by diet, in the presence of the above manifestations of microangiopathy and neuropathy.

Diabetic neuropathy is a characteristic clinical manifestation of diabetes mellitus; is observed in 12-70% of patients. Its frequency among patients significantly increases after 5 years or more of the existence of diabetes regardless of its type. However, the correlation of neuropathy with the duration of diabetes is not absolute, therefore, there is an opinion that the nature of compensation for diabetes mellitus affects the frequency of neuropathy, regardless of the degree of its severity and duration. The absence in the literature of clear data on the prevalence of diabetic neuropathy is largely due to insufficient information on its subclinical manifestations. Diabetic neuropathy includes several clinical syndromes: radiculopathy, mononeuropathy, polyneuropathy, amyotrophy, vegetative (autonomic) neuropathy and encephalopathy.

Radiculopathy is a rather rare form of somatic peripheral neuropathy, which is characterized by sharp shooting pains within one dermatome. This pathology is based on the demyelination of axial cylinders in the posterior roots and spinal cord columns, which is accompanied by a violation of deep muscular sensitivity, the disappearance of tendon reflexes, ataxia and instability in the Romberg pose. In some cases, the clinical picture of radiculopathy can be combined with the unevenness of the pupils, which is regarded as a diabetic pseudotubes. Diabetic radiculopathy must be differentiated from osteochondrosis and deforming spondylosis of the spine.

Mononeuropathy is the result of the defeat of individual peripheral nerves, including craniocerebral nerves. Spontaneous pain, paresis, sensitivity disorders, decrease and loss of tendon reflexes in the affected nerve zone are characteristic. The pathological process can damage the nerve trunks of III, V, VI-VIII pairs of cranial nerves. Much more often than others, III and VI couples suffer: approximately 1% of patients with diabetes mellitus have paralysis of extraocular muscles, which is combined with pain in the upper part of the head, diplopia and ptosis. The defeat of the trigeminal nerve (V pair) is manifested by attacks of intense pain in one half of the face. The pathology of the facial nerve (VII pair) is characterized by a one-sided paresis of the facial muscles, and the VIII pair is characterized by a decrease in hearing. Mononeuropathy is detected both against the background of long-standing diabetes mellitus, and impaired glucose tolerance.

Polyneuropathy is the most common form of somatic peripheral diabetic neuropathy, which is characterized by distal, symmetrical and mostly sensitive disorders. The latter are observed in the form of a "syndrome of socks and gloves," and much earlier and heavier this pathology manifests itself on the legs. Characteristic decrease in vibration, tactile, pain and temperature sensitivity, decrease and loss of Achilles and knee reflexes. The defeat of the upper extremities is less common and correlates with the duration of diabetes mellitus. Subjective sensations in the form of paresthesia and intense nocturnal pain can precede the appearance of objective signs of neurologic disorders. The pronounced pain syndrome and hyperalgesia, amplifying at night, cause insomnia, depression, loss of appetite, and in severe cases - a significant decrease in body weight. In 1974, M. Ellenberg described "diabetic polyneuropathic cachexia." This syndrome develops mainly in elderly men and is combined with intense pain with anorexia and weight loss, reaching 60% of the total body weight. Correlations with the degree of severity and type of diabetes are not noted. A similar case of the disease in an elderly woman with type II diabetes is published in Russian literature. Distal polyneuropathy often causes trophic disorders in the form of hyperhidrosis or anhidrosis, thinning of the skin, hair loss and much less frequent trophic ulcers, mainly on the feet (neurotrophic ulcers). Their characteristic feature is the safety of arterial blood flow in the vessels of the lower limbs. Clinical manifestations of diabetic somatic distal neuropathy usually undergo reverse development under the influence of treatment in the period from several months to 1 year.

Neuroarthropathy is a rather rare complication of sufficient polyneuropathy and is characterized by progressive destruction of one or more foot joints ("diabetic foot"). This syndrome was first described in 1868 by the French neuropathologist Charcot in a patient with tertiary syphilis. This complication is observed in many conditions, but most often in patients with diabetes mellitus. The prevalence of neuropathy is approximately 1 case for 680-1000 patients. Significantly, the syndrome of the "diabetic foot" develops against the background of long-term (more than 15 years) existing diabetes mellitus and mainly in the elderly. In 60% of patients, tarsus and tarsometry are observed, 30% are metatarsus and 10% are ankle. In most cases, the process is one-sided and only 20% of patients have a two-way process. Appear puffiness, hyperemia of the area of the corresponding joints, deformation of the foot, ankle joint, trophic ulcers of the soles in the absence of practically pain syndrome. The detection of the clinical picture of the disease is often preceded 4-6 weeks by trauma, stretching of the tendons, the formation of calluses with subsequent ulceration, and in case of defeat of the ankle joint - a fracture of the lower third of the shin. X-ray reveals massive bone destruction with sequestration and bone resorption, gross violation of articular surfaces and periarticular hypertrophic changes in soft tissues, subchondral sclerosis, osteophyte formation, intraarticular fractures. Often expressed x-ray destructive process is not accompanied by clinical symptoms. In the pathogenesis of neuroartropathy in elderly people, in addition to polyneuropathy, the ischemia factor is involved, due to the damage of the vessels of microcirculation and trunk. Attachment of infection can be accompanied by phlegmon and osteomyelitis.

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

Clinical manifestations of neuro-arthropathic and ischemic foot

Neuro-arthropathic	Ischemic foot
Good pulsation of blood vessels Normal foot tissues Corns in areas of compression Reduction or absence of the Achilles reflex The trend towards a "hammer-like" foot The "falling foot" (steppe) Charco's Warp Pain-free sores Heyroarthropathy (Greek cheir - hand)	Absence of pulsation Atrophy of soft tissues Thin, dry skin Normal Achilles reflex Redness of the feet Blanching of feet when they are lying down Painful ulcers

Another manifestation of neuro-arthropathy is diabetic heyropathy (neuroartropathy), whose prevalence is 15-20% in patients with a duration of type 1 diabetes 10-20 years. The first sign of the syndrome is a change in the skin of the hands. It becomes dry, waxy, compacted and thickened. Then it becomes difficult and it becomes impossible to unbend the little finger, and then the other fingers due to joint damage. Neuro-arthropathy usually precedes the appearance of chronic complications of diabetes mellitus (retinopathy, nephropathy). The risk of these complications in the presence of neuro-arthropathy increases 4-8 times.

Amiotrophy is a rare form of diabetic neuropathy. The syndrome is characterized by weakness and atrophy of the muscles of the pelvic girdle, pain in the muscles, a decrease and loss of knee reflexes, a violation of sensitivity in the area of the femoral nerves, and single fasciculations. The process begins asymmetrically, and then it becomes bilateral and occurs more often in elderly men with mild diabetes. Electromyography reveals the primary pathology of muscles and nerve damage. Muscle biopsy can detect the atrophy of individual muscle fibers, the safety of transverse striation, the absence of inflammatory and necrotic changes, the accumulation of nuclei under the sarcolemma. A similar pattern of muscle biopsy is observed with alcoholic myopathy. Diabetic amyotrophy should be differentiated from polymyositis, amyotrophic lateral sclerosis, thyrotoxic myopathy and other myopathies. The prognosis of diabetic amyotrophy is favorable: usually 1-2 years or earlier, recovery occurs.

The vegetative nervous system regulates the activity of smooth muscles, endocrine glands, heart and vessels. Violation of parasympathetic and sympathetic innervation is the basis for changes in the function of internal organs and the cardiovascular system. Clinical manifestations of autonomic neuropathy are observed in 30-70% of cases, depending on the surveyed contingent of patients with diabetes mellitus. Gastrointestinal pathology includes impaired function of the esophagus, stomach, duodenum and intestines. The violation of the function of the esophagus is expressed in a decrease in its peristalsis, in the expansion and decrease in the tone of the lower sphincter. Clinically, patients develop dysphagia, heartburn and occasionally ulceration of the esophagus. Diabetic gastropathy is observed in patients with a long duration of the disease and is manifested by vomiting food eaten the day before. X-ray reveals a decrease and paresis of peristalsis, an expansion of the stomach, a slowdown in its emptying. In 25% of patients, there is an increase and decrease in the tone of the duodenum and its bulb. The secretion and acidity of the gastric juice are reduced. In biopsies of the stomach, there are signs of diabetic microangiopathy, which are combined with the presence of diabetic retino- and neuropathy. Diabetic enteropathy is manifested by increased peristalsis of the small intestine and periodically arising diarrhea, more often at night (the frequency of defecation reaches 20-30 times a day). Diabetic diarrhea is usually not accompanied by weight loss. Correlation with the type of diabetes and the degree of its severity is not observed. In the biopsy specimens of the small intestine mucosa inflammatory and other changes were not revealed. The diagnosis is complicated in connection with the need for differentiation from enteritis of various etiology, suction disturbance syndromes, etc.

Neuropathy (atony) of the bladder is characterized by a decrease in its contractility in the form of retardation of urination, its reduction to 1-2 times a day, the presence of residual urine in the bladder, which contributes to its infection. Differential diagnosis includes prostatic hypertrophy, the presence of tumors in the abdominal cavity, ascites, multiple sclerosis.

Impotence is a frequent sign of autonomic neuropathy and may be the only manifestation of it observed in 40-50% of patients with diabetes mellitus. It can be temporary, for example, in case of decompensation of diabetes mellitus, but later becomes permanent. There is a decrease in libido, inadequate response, weakening of orgasm. Infertility in a man with diabetes mellitus can be associated with retrograde ejaculation, when the weakness of the sphincter of the bladder leads to a pellet in his sperm. In patients with diabetes mellitus with impotence there are no violations of the gonadotropic function of the pituitary gland, the testosterone content in the plasma is normal.

The pathology of sweating in the initial stages of diabetes is expressed in its amplification. With an increase in the duration of the disease, its decrease is observed, down to the anhidrosis of the lower extremities. At the same time, many sweating increases in the upper parts of the trunk (head, neck, chest), especially at night, which simulates hypoglycemia. In the study of skin temperature, there is a violation of oral-caudal and proximal-regular patterns and reactions to heat and cold. A kind of vegetative neuropathy is taste sweating, which is characterized by profuse sweating in the face, neck, upper chest area after a few seconds after taking some food products (cheese, marinade, vinegar, alcohol). It occurs infrequently. Local increase in sweating is due to impaired function of the upper cervical sympathetic ganglion.

Diabetic autonomic cardiac neuropathy (DVKN) is characterized by orthostatic hypotension, constant tachycardia, weak therapeutic effect on it, a fixed heart rhythm, hypersensitivity to catecholamines, painless myocardial infarction, and sometimes - sudden death of the patient. Postural (orthostatic) hypotension is the brightest sign of autonomic neuropathy. It manifests itself in the appearance of dizziness in patients with standing, general weakness, darkening in the eyes or impaired vision. This symptom complex is often regarded as a hypoglycemic condition, but in combination with a postural drop in blood pressure its origin is beyond doubt. In 1945, A. Rundles first linked postural hypotension with neuropathy in diabetes. Manifestations of postural hypotension may be intensified after taking antihypertensive drugs, diuretics, tricyclic antidepressants, phenothiazine drugs, vasodilators, and nitroglycerin. The introduction of insulin can also aggravate postural hypotension, reducing venous return or damaging the permeability of the capillary endothelium with a decrease in plasma volume, while the development of heart failure or nephrotic syndrome reduces hypotension. It is believed that its occurrence is due to dulling of the plasma renin reaction on the rise due to deterioration of the sympathetic innervation of the juxtaglomerular apparatus, as well as to lower basal and stimulated (standing) levels of plasma noradrenaline or a baroreceptor defect.

Patients with diabetes mellitus complicated by DVKN, at rest, there is an increase in heart rate to 90-100, and sometimes up to 130 beats per minute. Persistent tachycardia, which is not amenable to therapeutic effects in diabetic patients, is due to parasympathetic insufficiency and can serve as a manifestation of the early stage of autonomic cardiac disorders. Vagal innervation of the heart is the reason for the loss of the ability of normal variation of the heart rhythm in diabetic cardiopathy and, as a rule, precedes the sympathetic denervation. Reducing the variation of cardiointervals at rest can serve as an indicator of the degree of functional disorders of the autonomic nervous system.

Total denervation of the heart is rare and characterized by a fixed frequent heart rate. Typical pain in the development of myocardial infarction is uncharacteristic for patients suffering from DVIC. In most cases, patients do not feel pain or are atypical at the time of it. It is assumed that the cause of painless heart attacks in these patients is damage to the visceral nerves that determine the pain sensitivity of the myocardium.

M. McPage and PJ Watkins reported 12 cases of sudden "cardiopulmonary arrest" in 8 young people suffering from diabetes with severe autonomic neuropathy. Clinico-anatomical data on myocardial infarction, cardiac arrhythmia or hypoglycemic state was not. In most cases, the cause of the attack was the inhalation of narcotic drugs with general anesthesia, the use of other drugs or bronchopneumonia (5 attacks occurred immediately after giving anesthesia). Thus, cardiorespiratory arrest is a specific sign of autonomic neuropathy and may be fatal.

Diabetic encephalopathy. Persistent changes in the central nervous system in young people are usually associated with acute metabolic disorders, and in old age are also determined by the severity of the atherosclerotic process in the vessels of the brain. The main clinical manifestations of diabetic encephalopathy are disorders of mental activity and organic cerebral symptoms. The most common memory loss in diabetic patients is memory. Particularly pronounced influence on the development of mnestic disorders is exerted by hypoglycemic conditions. Violations of mental activity can also be manifested by increased fatigue, irritability, apathy, crying, sleep disturbance. Severe mental disorders in diabetes mellitus are rare. Organic neurological symptoms can be manifested by diffuse microsymptomatics, which indicates a diffuse lesion of the brain, or a rough organic symptomatology indicating the presence of a lesion of the brain. The development of diabetic encephalopathy is determined by the development of degenerative changes in the neurons of the brain, especially during hypoglycemic conditions, and ischemic foci in it, associated with the presence of microangiopathy and atherosclerosis.

Skin pathology. For patients with diabetes, diabetic dermopathy, lipoid necrobiosis and diabetic xanthoma are more common, but none of them is absolutely specific for diabetes.

Dermopathy ("atrophic spots") is expressed in the appearance on the anterior surface of the shins of symmetrical reddish-brown papules with a diameter of 5-12 mm, which then turn into pigmented atrophic spots of the skin. Dermopathy is more often detected in men with a long duration of diabetes mellitus. The pathogenesis of dermopathy is associated with diabetic microangiopathy.

Lipoid necrobiosis is much more common in women and in 90% of cases it is located on one or both legs. In other cases, the place of defeat is the trunk, hands, face and head. The frequency of lipid necrobiosis is 0.1-0.3% in relation to all patients with diabetes. The disease is characterized by the appearance of skin areas of red-brown or yellow color ranging in size from 0.5 to 25 cm, often oval. The skin lesions are surrounded by the erythematous border of the dilated vessels. The deposition of lipids and carotene causes the yellow color of affected areas of the skin. Clinical signs of lipid necrobiosis may for several years outstrip the development of type I diabetes or be detected against its background. As a result of examination of 171 patients with lipoid necrobiosis, 90% of them had a relationship with diabetes mellitus: in some patients necrobiosis developed before diabetes or against it, the other part of patients had a hereditary predisposition to it. Histologically, the skin shows signs of obliterating endarteritis, diabetic microangiopathy, and secondary necrobiotic changes. The destruction of elastic fibers, the elements of the inflammatory reaction in the necrosis areas and the appearance of giant cells were observed electronically. One of the reasons for lipoid necrobiosis is an increased platelet aggregation under the influence of various stimuli, which, along with the proliferation of the endothelium, causes thrombosis of small vessels.

Diabetic xanthoma develops as a result of hyperlipidemia, and the main role is played by an increase in the content of chylomicrons and triglycerides in the blood. Yellowish plaques are localized mainly on the flexural surfaces of the extremities, chest, neck and face and consist of a cluster of histiocytes and triglycerides. In contrast to the xanth, observed with familial hypercholesterolemia, they are usually surrounded by the erythematous fringe. Elimination of hyperlipidemia leads to the disappearance of the diabetic xanthoma.

Diabetic bladder refers to rare skin lesions in diabetes mellitus. This pathology was first described in 1963 by RP Rocca and E. Regeuga. Bubbles appear suddenly, without redness, on the fingers and toes, and also on the foot. Their dimensions vary from a few millimeters to several centimeters. The bubble can increase for several days. Bubble fluid is transparent, sometimes hemorrhagic and always sterile. The diabetic bladder disappears independently (without autopsy) for 4-6 weeks. A more frequent occurrence of a diabetic bladder in patients with signs of diabetic neuropathy and a long duration of diabetes, as well as against diabetic ketoacidosis, was noted. Histological examination revealed intradermal, subepidermal, and subroginal localization of the bladder. The pathogenesis of the diabetic bladder is unknown. Differentiate it from pemphigus and impaired metabolism of porphyrin.

Ring-shaped granuloma Darya can occur in patients with diabetes mellitus ^{: the} elderly, more often in men. On the trunk and extremities appear rashes in the form of coin-like edemas of pink or reddish-yellowish color, prone to rapid peripheral growth, fusion and formation of rings and bizarre polycyclic figures fringed with a dense and elevated margin. The coloring of the central several zapadayuschey zone is not changed. Patients complain of a slight itch or burning sensation. The course of the disease is long, relapsing. Usually, rashes after 2-3 weeks disappear, and they are replaced by new ones. Histologically, there are edema, vasodilation, perivascular infiltrates from neutrophils, histiocytes, and lymphocytes. The pathogenesis of the disease is not established. Provoking factors may serve as allergic reactions to sulfanilamide and other drugs.

Vitiligo (depigmented symmetrical skin areas) is detected in patients with diabetes mellitus in 4.8% of cases compared with 0.7% of the total population, and in women it is 2 times more likely. Vitiligo is combined, as a rule, with type I diabetes mellitus, which confirms the autoimmune genesis of both diseases.

Much more often than in other diseases, diabetes mellitus is accompanied by furuncles and carbuncles, which usually occur against decompensation of the disease, but can also be a manifestation of latent diabetes or precede a violation of glucose tolerance. A greater propensity of diabetes patients to fungal diseases is expressed in the manifestations of epidermophytosis, which is found mainly in the interdigital intervals of the feet. More often than those with unbroken tolerance to glucose, itchy dermatoses, eczema, itching in the genital area are revealed. The pathogenesis of this skin pathology is associated with a violation of intracellular glucose metabolism and a decrease in resistance to infection.

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

Pathology of the organ of vision in diabetes mellitus

Various violations of the function of the organ of vision, up to blindness, occur in patients with diabetes mellitus 25 times more often than in the general population. Among patients with blindness, 7% are patients with diabetes mellitus. Disorders of the function of the organ of vision may be due to damage to the retina, iris, cornea: the lens, optic nerve, extraocular muscles, orbital tissue, etc.

Diabetic retinopathy is one of the main causes of impaired vision and blindness in patients. Various manifestations (against the backdrop of a 20-year duration of diabetes mellitus) are found in 60-80% of patients. Among patients with type I diabetes with a duration of disease more than 15 years, this complication is observed in 63-65%, of which proliferating retinopathy - in 18-20% and complete blindness - in 2%. In patients with type II diabetes, its symptoms develop with a shorter duration of diabetes. 7.5% of patients suffer from significant visual impairment, and half of them suffer complete blindness. The risk factor for the development and progression of diabetic retinopathy is the duration of diabetes mellitus, since there is a direct correlation between the incidence of this syndrome and the duration of type I diabetes. According to V. Klein et al., In a survey of 995 patients, it was found that the incidence of visual impairment increases from 17% in patients with a duration of diabetes not exceeding 5 years, to 97.5% with a duration of up to 10-15 years. According to other authors, the cases of retinopathy fluctuate up to 5% during the first 5 years of the disease, up to 80% - with a duration of diabetes more than 25 years.

In children, regardless of the duration of the disease and the degree of its compensation, retinopathy is detected much less frequently and only in the post-pubertal period. This fact allows us to assume the protective role of hormonal factors (STH, somatomedin "C"). The likelihood of edema of the optic nerve disc also increases with the duration of diabetes: up to 5 years - its absence and after 20 years - 21% of cases; on average, it is 9.5%. Diabetic retinopathy is characterized by the expansion of venules, the appearance of microaneurysms, exudates, hemorrhages and proliferative retinitis. Microanerusms of capillaries and, especially, venules are specific changes in the retina in diabetes mellitus. The mechanism of their formation is associated with tissue hypoxia, caused by metabolic disorders. Characteristic is the tendency to increase the number of microaneurysms in the pre-sacral area. Long-existing microaneurysms may disappear, due to their rupture (hemorrhage) or thrombosis and organization due to the deposition of proteins of hyaline-like material and lipids in them. Exudates in the form of white-yellow, waxy foci of turbidity are localized usually in the area of hemorrhages in various parts of the retina. Approximately 25% of patients with diabetic retinopathy experience changes in the form of proliferative retinitis. Usually they have against a background of microaneurism, hemorrhages in the retina and exudates, hemorrhages appear in the vitreous humor, which is accompanied by the formation of connective tissue-vascular proliferative cords that penetrate from the retina into the vitreous. Subsequent shrinkage of connective tissue causes retinal detachment and blindness. The process of the formation of new vessels goes also in the retina, with a tendency to damage the visual disc, which causes a decrease or total loss of vision. Proliferating retinitis has a direct correlation with the duration of diabetes mellitus. Its signs are usually found 15 years after the detection of diabetes in young patients and in 6-10 years - in adults. A significant frequency of this complication is observed with a long duration of the disease in patients who fell ill at a young age. In many patients, proliferative retinitis is combined with clinical manifestations of diabetic nephropathy.

According to the modern classification (according to E. Kohner and M. Porta), there are three stages of diabetic retinopathy. Stage I - non-proliferative retinopathy. It is characterized by the presence of microaneurysms, hemorrhages, retinal edema, exudative foci in the retina. II stage - pre-proliferative retinopathy. Characterized by the presence of venous anomalies (crispness, crimp, doubling and / or pronounced fluctuations in the caliber of vessels), a large number of hard and "cotton" exudates, intra-retinal microvascular anomalies, a number of major retinal hemorrhages. Stage III - proliferative retinopathy.

It is characterized by neovascularization of the optic nerve disk and / or other parts of the retina, hemorrhages in the vitreous with the formation of fibrous tissue in the area of preretinal hemorrhages. The cause of blindness in diabetics is vitreous hemorrhage, maculopathy, retinal detachment, glaucoma and cataract.

Diabetic retinopathy (including proliferative) is characterized by a wavy course with a tendency to spontaneous remissions and a periodic exacerbation of the process. Progression of retinopathy is facilitated by decompensation of diabetes mellitus, arterial hypertension, renal failure and largely pregnancy, as well as hypoglycemia. Diseases of the eyelids (blepharitis, cholazion, barley) are not specific for diabetes, but are often combined with it and characterized by persistent recurrent course, caused by a violation of tissue metabolism of glucose and a decrease in the immunobiological properties of the body.

Change in the vessels of the conjunctiva in diabetic patients is expressed in the presence of phlebopathy (lengthening and widening of the venular ends of the capillaries, microaneurysm) and sometimes exudates.

Changes in the cornea are expressed in epithelial punctate keratodystrophy, fibrous and uveal keratitis, recurrent corneal ulcers, which usually do not cause a significant decrease in vision. With insufficient compensation for diabetes mellitus, the deposition of glycogen-like material in the pigment epithelium of the posterior surface of the iris is sometimes observed, which causes degenerative changes and depigmentation of its corresponding sites. Against the background of proliferative retinopathy in 4-6% of patients there is rubidosis of the iris, expressed in the growth of newly formed vessels on its anterior surface and in the anterior chamber of the eye, which may be the first cause of hemorrhagic glaucoma.

Cataract, distinguish metabolic (diabetic) and senile species. The first develops in poorly compensated insulin-dependent patients and is localized in the subcapsular layers of the lens. The second - in elderly people, both in diabetics and healthy people, but ripens much faster in the first, which explains the need for more frequent surgical interventions. The pathogenesis of diabetic cataract is associated with a hyperglycemia-induced conversion of glucose to sorbitol in the lens tissues. Excessive accumulation of them causes cellular edema, which directly or indirectly changes the metabolism of myonosite, which leads to the development of cataracts.

Glaucoma occurs in 5% of patients with diabetes mellitus compared with 2% healthy. Increase in intraocular pressure by more than 20 mm Hg. Art. Can damage the function of the optic nerve and cause visual impairment. Diabetes mellitus is often combined with various types of glaucoma (open-angle, convulsive and due to proliferative retinopathy). Typical for patients is an open-ended form, characterized by a difficult outflow of chamber moisture due to obliteration of the drainage apparatus of the eye. Changes in it (helmet canal) are similar to manifestations of diabetic microangiopathy.

Violation of the function of the oculomotor muscles (ophthalmoplegia) is caused by damage to the III, IV and VI pairs of cranial oculomotor nerves. The most characteristic signs are diplopia and ptosis, which are more common in patients with type I diabetes. In some cases, ptosis and diplopia may be the first manifestations of clinical diabetes. The cause of ophthalmoplegia is diabetic mononeuropathy.

Transient disturbance of visual acuity is observed in diabetic patients on the background of initial insulin treatment due to significant fluctuations in glycemia, and also as one of the signs preceding the development of cataracts. Uncompensated course of diabetes with significantly hyperglycemia is accompanied by increased refraction, due to an increase in the refractive capacity of the lens. Myopia usually develops before the onset of cataracts. The aforementioned changes in visual acuity can to a large extent be due to the accumulation of sorbitol and liquid in the lens. It is known that hyperglycemia enhances in the lens the conversion of glucose to sorbitol, which has a pronounced osmolarity that contributes to fluid retention. This in turn can cause changes in the shape of the lens and its refractive properties. Reduction of glycemia, especially against the background of insulin treatment, often contributes to the weakening of refraction. In the pathogenesis of these disorders it is possible to reduce the secretion of moisture in the anterior chamber, which helps to change the position of the lens.

The defeat of orbital tissues is rare and is caused by a bacterial or fungal infection. In this process, both orbital and periorbital tissues participate in the process. In patients, there appear proptosis of the eyeball, ophthalmoplegia (up to the central fixation of the eye), deterioration of vision, pain syndrome. A greater danger to life is the involvement of the cavernous sinus in the process. Treatment conservative - antibacterial and antifungal drugs.

Atrophy of the optic nerves is not a direct consequence of diabetes, but it is observed in patients with a long duration of the disease in the presence of diabetic proliferative retinopathy and glaucoma.

To diagnose the pathology of the organ of vision, it is necessary to determine its severity and margins, with the help of biomicroscopy of the anterior part of the eye to detect vascular changes in the conjunctiva, limbus, iris and degree of clouding of the lens. Direct ophthalmoscopy, fluorescent angiography allows you to assess the state of the retinal vessels. Patients with diabetes require repeated examinations by an ophthalmologist 1-2 times a year.

Heart failure in diabetes mellitus

Cardiovascular pathology is the main factor causing high lethality in patients with diabetes mellitus. The defeat of the heart in the disease can be due to diabetic microangiopathy, myocardial dystrophy, autonomic diabetic cardiac neuropathy, and coronary atherosclerosis. In addition, in patients with diabetes mellitus, bacterial endocarditis, myocardial abscesses on the background of sepsis, pericarditis in chronic renal insufficiency and hypokalemic myocarditis in ketoacidosis are significantly more frequent than in diabetic patients.

Specific diabetes mellitus for microvasculature vessels - diabetic microangiopathy - is found in the cardiac muscle. This process is histologically characterized by thickening of the basement membrane of the capillaries, venules and arterioles, proliferation of the endothelium, the appearance of aneurysms. In the pathogenesis of the thickening of the basal membrane, excessive deposition of PAS-positive substances, premature aging of pericytes, accumulation of collagen take part. Diabetic microangiopathy, found in the myocardium, contributes to the disruption of its functional activity.

Among patients with idiopathic microcardiopathy, the relative frequency of patients with diabetes mellitus is significantly increased. At the same time, small vessels are affected (with unchanged large coronary arteries), extravascular accumulation of collagen, triglycerides and cholesterol between myofibrils, which is not accompanied by hyperlipidemia. Clinically, myocardiopathy is characterized by a shortened period of left ventricular ejection, an elongation of the stress period, an increase in the diastolic volume. The changes inherent in myocardiopathy can contribute to the frequent occurrence of heart failure during an acute period of myocardial infarction and high lethality. The pathogenesis of diabetic myocardial dystrophy is caused by metabolic disorders that are absent in healthy individuals and well compensated diabetic patients. Absolute or relative deficiency of insulin disrupts the transport of glucose through the cell membrane, so most of the energy expenditure of the myocardium is compensated for by increased utilization of free fatty acids, which are formed with increased lipolysis (in conditions of insulin deficiency). Insufficient oxidation of FFA is accompanied by an increased accumulation of triglycerides. An increase in the tissue level of glucose-6-phosphate and fructose-6-phosphate causes the accumulation of glycogen and polysaccharides in the cardiac muscle. Compensation for diabetes contributes to the normalization of metabolic processes in the myocardium and to the improvement of its function.

Diabetic autonomic cardiac neuropathy is one of the clinical manifestations of diabetic vegetative neuropathy, which also includes the syndrome of gastropathy, enteropathy, atony of the bladder, impotence and sweating. DVCC is characterized by a number of specific signs, including a constant tachycardia, a fixed heart rhythm, orthostatic hypotension, hypersensitivity to catecholamines, painless myocardial infarction and "cardiopulmonary arrest" syndrome. It is caused by the defeat of the parasympathetic and sympathetic parts of the central nervous system. Initially, the parasympathetic innervation of the heart is disturbed, which manifests itself in the previously mentioned tachycardia to 90-100 beats / min, and in some cases up to 130 beats / min, which is not amenable to therapeutic effects. Weakening of the vagus function is also a cause of disturbance of the regulation of the heart rhythm, manifested in the absence of respiratory variation of heart intervals. The defeat of sensitive nerve fibers is also explained by relatively frequent myocardial infarctions in these patients with an atypical clinic characterized by the absence or weak manifestation of pain syndrome. With the increase in the duration of diabetes mellitus, the changes in sympathetic innervation of smooth muscle fibers of peripheral vessels are associated with parasympathetic disorders, which is manifested in the appearance of orthostatic hypotension in patients. In this case, patients feel dizzy, darkening in the eyes and flashing "flies". This condition passes by itself, or the patient is forced to accept the starting position. According to AR Olshan et al., Orthostatic hypotension in patients occurs due to a decrease in the sensitivity of baroreceptors. N. Oikawa et al. Believe that in response to rising, the level of plasma adrenaline decreases.

Another rather rare manifestation of a violation of parasympathetic failure is cardiopulmonary insufficiency, described by M. McPage and PJ Watkins in patients with type I diabetes mellitus and characterized by a sudden cessation of cardiac activity and respiration. Of the 8 patients described, 3 died during this condition. In most cases, the cause of death is the inhalation of a narcotic analgesic during anesthesia for surgical intervention. During autopsy, the cause of death was not established. The cardiopulmonary stop, according to the authors, has a primary pulmonary origin due to a decrease in the sensitivity of the respiratory center and hypoxia in patients with autonomic neuropathy, since the carotid bodies and chemoreceptors are innervated by glossopharyngeal and vagus nerves. As a result of hypoxia, hypotension occurs, cerebral blood flow decreases, and respiratory arrest of the central genesis occurs, as evidenced by the rapid response of patients to respiratory stimulants. Samples that detect violations of the parasympathetic system are based on a decrease in the variation of cardiointervals (decrease in respiratory arrhythmia) caused by previously described changes in nervous tissue. Most often for this purpose, tests are used with recording heart rate changes in normal and deep breathing, a modified Valsalva test, Ewing's test and some others. Violations of sympathetic innervation of the heart are detected with the help of an orthostatic test and other tests. All listed methods of diagnostics differ relative simplicity of execution, non-invasiveness and rather high informativeness. They can be recommended for use both in hospitals and in polyclinic conditions.

Atherosclerosis of the coronary arteries. The localization of coronary atherosclerosis in diabetic patients is the same as in patients without diabetes, and is manifested primarily by proximal coronary artery involvement. The only difference is the occurrence of coronary atherosclerosis in diabetic patients at a young age with a more severe manifestation. Apparently, with diabetes much less collateral, as the angiography data of the main coronary arteries in patients with coronarosclerosis in the presence and absence of diabetes are the same. In accordance with experimental studies, it is believed that endogenous or exogenous hyperinsulinemia plays a leading role in the rapid progression of atherosclerosis in diabetic patients: insulin, suppressing lipolysis, enhances the synthesis of cholesterol, phospholipids and triglycerides in the walls of blood vessels. Permeability of endothelial cells resistant to insulin changes under the influence of catecholamines (against the background of fluctuations in glycemia), which facilitates the contact of insulin with smooth muscle cells of artery walls, which stimulates the proliferation of these cells and the synthesis of connective tissue in the vascular wall. Lipoproteins are captured by smooth muscle cells and penetrate into the extracellular space, where they form atherosclerotic plaques. This hypothesis explains the threshold relationship between the level of glucose in the blood and atherosclerosis, as well as the fact that the risk factors equally affect the development of atherosclerosis in diabetics and in healthy people. It is known that type II of the disease is characterized by an increase in the basal level of insulin and an increase in the incidence of atherosclerosis and coronary heart disease (CHD). When comparing patients with diabetes mellitus and coronary artery disease with diabetic patients without it, an increase in the insulin response to oral glucose administration and a more pronounced increase in insulin secretion after an oral test with tolbutamide were found. At type II diabetes in combination with atherosclerosis, the ratio of insulin / glucose is increased. As a result of the study of patients with atherosclerosis of coronary, cerebral and peripheral arteries without diabetes, an increase in the insulin response to oral glucose loading was also observed. Obesity is accompanied by hyperinsulinemia, both in the absence and in the presence of diabetes. The risk of ischemic heart disease is much greater if there is obesity of the android type.

Myocardial infarction. In comparison with the prevalence of it in a population in patients with diabetes mellitus of similar age, it occurs 2 times more often. Coronary artery disease is the main cause of death in patients with type 2 diabetes. Mortality due to myocardial infarction is extremely high in such patients and reaches 38% in the first days after its occurrence, and 75% in the next 5 years. The clinical course of myocardial infarction in diabetics has the following features: the occurrence of extensive heart attacks, often observed thromboembolic complications of heart failure, the prevalence of recurrent myocardial infarction and an increased percentage of lethality in the acute period, and often an atypical infarction clinic with mild and absent pain syndrome. The frequency of this complication directly correlates with the duration of diabetes (especially in patients with type I), the age of patients, the presence of obesity, hypertension, hyperlipidemia and, to a lesser extent, the severity of diabetes and the nature of its treatment. In many cases, type II diabetes debuts with myocardial infarction.

The greatest difficulties in its diagnosis are atypical manifestations. About 42% of patients during myocardial infarction do not feel pain (compared with 6% of patients without diabetes) or it is atypical and mild. Signs of a heart attack in diabetic patients can be a sudden occurrence of general insufficiency, pulmonary edema, unmotivated nausea and vomiting, decompensation of diabetes mellitus with an increase in glycemia and ketoacidosis of an unknown genesis, disturbance of the heart rhythm. Studies of diabetic patients who died from myocardial infarction showed that 30% of them had previously suffered an undiagnosed infarction, while 6.5% had changes that indicated 2 or more painless heart attacks that had been carried out before. The data from the Framingham survey indicate that the infarction detected in a random ECG study was observed in 39% of diabetic patients and 22% of patients without it. The occurrence of painless myocardial infarctions in diabetes mellitus is now often associated with autonomic cardiac neuropathy and affection of sensitive fibers of the afferent nerves. This hypothesis was confirmed by the study of nerve fibers in patients who died during the painless infarction. In the control group of the deceased (patients with and without a pain heart attack, with or without diabetes), no similar changes were detected in autopsy.

In the acute period of myocardial infarction, basal hyperglycemia occurs in 65-100% of patients, which can be the result of the release of catecholamines and glucocorticoids in response to a stressful situation. The significant increase in the secretion of endogenous insulin observed in this case does not eliminate hyperglycemia, since the content of free fatty acids in the blood that suppress the biological effect of insulin increases. Violation of tolerance to carbohydrates in the acute period of myocardial infarction often has a transitory character, but almost always indicates a risk of developing diabetes. Subsequent examination (after 1-5 years) of patients with transient hyperglycemia occurring in the acute period of infarction indicates that 32-80% of them subsequently detected NTG or clinical diabetes.

Renal damage in diabetes

Diabetic nephropathy (Kimmelstil-Wilson syndrome, intercapillary glomerulosclerosis) is a manifestation of late diabetic syndrome. It is based on various processes, including nodular and diffuse glomerulosclerosis, thickening of the basement membrane of the capillaries of the renal glomeruli, arterio- and arteriolosclerosis, as well as tubular interstitial fibrosis.

This complication is one of the main causes of death among diabetic patients, increasing by 17 times in comparison with the general population. In about half of all cases, diabetic nephropathy develops in patients with diabetes mellitus before the age of 20 years. Its clinical manifestations are found after 12-20 years of illness. However, some changes in kidney function and anatomical disorders develop much earlier. So, even with the onset of diabetes mellitus, there is an increase in the size of the kidneys, the lumen of the tubules, and the glomerular filtration rate. After compensating for diabetes, the size of the kidneys is normalized, but the glomerular filtration rate remains elevated even after 2-5 years, when a thickening of the basal membrane of the glomerular capillaries is detected in the puncture biopsy, which indicates the initial (histological) stage of diabetic nephropathy. Clinically, there are no other changes in the 12-18 year period in patients, despite the progression of anatomical disorders.

The first symptom of diabetic nephropathy is transitory proteinuria, which occurs, as a rule, with physical exertion or orthostasis. Then it becomes constant at a normal or slightly reduced glomerular filtration rate. A significant increase in proteinuria, exceeding 3 g / day and sometimes reaching 3 g / L, is accompanied by a disproteinemia characterized by hypoalbuminemia, a decrease in IgG, hypergammaglobulinemia and an increase in alpha2-macroglobulins. At the same time, 40-50% of the free-radicals develop a nephrotic syndrome, hyperlipidemia appears according to type IV according to Fridriksen. After 2-3 years of the existence of permanent proteinuria, azotemia appears, the content of urea increases in the blood, creatinine decreases, glomerular filtration decreases.

Further progression of the disease leads after another 2-3 years to the development of a clinical syndrome of renal failure in half of patients, especially a rapid increase in the office is observed in patients with severe proteinuria in combination with nephrotic syndrome. With the development of renal failure, the glomerular filtration rate sharply decreases, the levels of residual nitrogen (more than 100 mg%) and creatinine (more than 10 mg%) increase, hypo- or normochromic anemia is revealed. At 80-90% of patients at this stage of the disease, blood pressure is significantly increased. The genesis of arterial hypertension is mainly due to sodium retention and hypervolemia. Heavy arterial hypertension can be combined with heart failure in the right ventricular type or complicated by pulmonary edema.

Renal failure is usually accompanied by hyperkalemia, which can reach 6 mmol / l or more, which is manifested by characteristic ECG changes. Its pathogenesis can be caused by extrarenal and renal mechanisms. The first include a decrease in the content of insulin, aldosterone, norepinephrine and hyperosmolarity, metabolic acidosis, beta-adrenoblockers. To the second - reduction of glomerular filtration, interstitial nephritis, giporeninemic hypoaldosteronism, inhibitors of prostaglandins (indomethacin) and aldactone.

The clinical course of diabetic nephropathy is complicated by infection of the urinary tract, chronic pyelonephritis, which contributes to the development of interstitial nephritis. Chronic pyelonephritis is often asymptomatic and manifests itself as a worsening of the clinical course of diabetic nephropathy or decompensation of diabetes mellitus. The latter (according to sectional data - 110%) is combined with necrotic papillitis, which can manifest itself in severe form (1%) with an increase in body temperature, macrogemuria, renal colic, and also in a latent form, often undiagnosed, since its only manifestation is microhematuria . In some patients with renal insufficiency, the course of diabetes mellitus changes, which is expressed in a decrease in the daily requirement for insulin, caused by a decrease in appetite of patients due to nausea and vomiting, and also due to a decrease in insulin degradation in the kidneys and an increase in the half-life of the patient.

The clinical course and manifestation of diabetic nephropathy in patients with types I and II types of diabetes have significant differences. In type II diabetes, nephropathy progresses much more slowly and is not the main cause of death.

The features of the clinical manifestation of diabetic nephropathy in various types of diabetes are apparently due to the varying degree of involvement in its pathogenesis of reversible or irreversible changes in the renal tissue.

Pathogenesis of diabetic nephropathy according to D'Elia.

Reversible changes

1. Increase glomerular filtration without increasing renal plasma flow.
2. Proteinuria with hyperglycemia, insulin deficiency, increasing with exercise and orthostasis.
3. Accumulation in mesangium of immunoglobulins, products of protein decay, mesangium hyperplasia.
4. Lowering the ability of the distal tubules to secrete hydrogen ions.

Irreversible changes

1. Increased synthesis of collagen in the basal membrane.
2. Hyaline sclerosis of arterioles with damage to the juxtaglomerular apparatus.
3. Atherosclerosis of the arteries with renal involvement.
4. Necrosis of the papillae.

According to the nature of the clinical course, diabetic nephropathy is divided into latent, clinically manifested, and terminal forms. The latter is characterized by uraemia. When subdividing nephropathy, the stage uses the Mogensen classification (1983), which is based on laboratory-clinical data.

1. The stage of hyperfunction occurs during the onset of diabetes mellitus and is characterized by hyperfiltration, hyperperfusion, renal hypertrophy and normoalbuminuria (<30 mg / day).
2. Stage of initial changes in the kidneys. It is characterized by thickening of the glomerular basement membrane, expansion of mesangium, hyperfiltration and normoalbuminuria (<30 mg / day). These changes occur when the duration of diabetes is more than 5 years.
3. The stage of initiating ND develops after 5 years or more. It is characterized by the appearance of microalbuminuria (from 30 to 300 mg / day), normal or elevated GFR.
4. The stage of marked ND occurs in 10-15 years of SD existence. Characteristic proteinuria (more than 0.5 g protein per day), arterial hypertension, decreased GFR. These signs are caused by sclerosis of 50-70% of the glomeruli.
5. Stage of chronic renal failure (uremia). In this case, GFR decreases (<10 ml / min). Changes in the kidneys correspond to total glomerulosclerosis, which develops with the duration of DM 15-20 years.

I-III stages of diabetic nephropathy are preclinical forms of the disease.

IV stage of diabetic nephropathy is characterized by the appearance of proteinuria, a decrease in the concentration ability of the kidneys, the presence of hypoisostenuria, edema, persistent hypoproteinemia, hyperlipidemia, increased blood pressure. In this case, the nitrogen excretory function is reduced.

V stage of diabetic nephropathy is a nephrosclerotic stage, expressed in chronic renal insufficiency of the third degree (edema, hypertension, hypoisostenuria, cylindruria, erythrocyturia, creatinemia, azotemia, urea increase in blood, uremia). Characteristic is the "improvement" in the course of diabetes mellitus: glucosuria, hyperglycemia, daily insulin requirements decrease, which is due to a decrease in the activity of the insulinase enzyme in the kidney, which cleaves insulin in the norm. Nephropathy (IV-V stage), as a rule, is combined with diabetic retinopathy II, III stages.