Diabetes mellitus

Diabetes mellitus is a multisystem chronic disease in which all types of metabolism are disturbed.It is characterized by impaired secretion or action of insulin, accumulation of glucose in the blood (hyperglycemia), urine (glucosuria) and development of complications.

Endocrinologists with many years of experience in the field of endocrinology work in the modern clinic.Doctors will be able to correctly determine the degree of compensation of diabetes mellitus, identify existing complications and prescribe or adjust a treatment program.

How does glucose metabolism normally occur?

Glucose is the main source of energy in the body.It enters the body with food, mainly carbohydrates, or is synthesized through a series of metabolic reactions from fats and proteins.Excess glucose accumulates in the liver and muscles in the form of glycogen and is used when needed.

All tissues in the human body are divided into insulin-dependent (muscles, adipose tissue, cardiomyocytes) and insulin-independent (brain, red blood cells, cornea, liver, kidneys).In order for glucose to pass into the cell of insulin-dependent tissue and be used in cellular metabolism, insulin is required.It is produced in the β-cells of the pancreas.Insulin acts as a key that opens the lock for glucose to enter the cell.Insulin-independent tissues obtain glucose by simple diffusion, passively.

When everything in the body works properly, the process of glucose entering the insulin-dependent tissues proceeds dynamically and no problems arise.When the production of insulin is disturbed (for example, when the pancreas is damaged) or the mechanism of its action on the cell is disturbed (the cellular "lock" is broken), glucose begins to accumulate in the body and cellular starvation develops in the cells.

Below we will look at what happens when glucose builds up in the body and the different types of diabetes.

Classification

Experts distinguish several main types of diabetes.We will focus on the four most common:

• Type I (old name: insulin-dependent);
• Type II (old name: insulin-independent);
• gestational;
• Symptomatic.

Let's look at each type in more detail.

Diabetes mellitus type I

This type of diabetes mellitus develops as a result of damage to the β-cells of the pancreas, the source of insulin in the body, which leads to a state of absolute insulin deficiency.One of the frequent causes of cell damage is the development of an autoimmune process, when the cells of the pancreas begin to be perceived by the body as foreign.Antibodies accumulate against them, which completely destroy the source of insulin.

Other causes of pancreatic beta cell destruction:

• the effects of chemicals (nitrosamine, pesticides, some drugs);
• infectious lesions (measles, rubella, cytomegalovirus);

The disease develops when more than 80% of the cells are destroyed.

Diabetes mellitus type I is characteristic of young people and often debuts at an early age, in an acute form, with a rapid increase in clinical symptoms.

Diabetes mellitus type II

Diabetes mellitus type II (old name: non-insulin dependent) develops as a result of a violation of the receptor apparatus of the cells, due to which insulin resistance is formed in the body.

In this type of diabetes, insulin is produced in the required volume, but the insulin-dependent cells stop responding to it.Relative insulin deficiency leads to reduced utilization of glucose by muscle and adipose tissue, which contributes to the development of hyperglycemia.

The causes of type II diabetes are:

• hereditary predisposition;
• overeating, obesity;
• lack of physical activity;
• a state of chronic stress.

Table 1. Comparative characteristics of type I and type II diabetes mellitus.

Sign	Type I	Type II
Distribution	15%	85%
Onset of the disease	Most often in childhood or adolescence	Middle and old age
	Sharp	Long term progressive
Development of symptoms	quickly	slowly
Phenotype (appearance)	skinny	obesity
Insulin level	It's missing (or sharply reduced)	Elevated
Insulin resistance	-	+
Lack of insulin	Absolutely (no insulin at all)	Relatively (insulin is present but does not enter the cells)
Ketoacidosis	+	-

Gestational (diabetes during pregnancy)

Physiological pregnancy is characterized by two significant changes in glucose metabolism:

• Constant supply of glucose to the placenta and fetus.During pregnancy, due to the increased consumption of glucose, its level in the body decreases faster than in a non-pregnant woman.
• A decrease in tissue sensitivity to insulin in the second trimester of pregnancy, which leads to the formation of insulin resistance.

This condition is caused by an excess of hormones: progesterone, cortisol, prolactin, which have a counterinsular effect (block the action of insulin).This reduces the sensitivity of fat and muscle tissue to insulin.

Physiological pregnancy is characterized by both insulin resistance and a compensatory increase in pancreatic β-cell function that helps maintain optimal glucose metabolism.In women with impaired glucose tolerance, the compensatory capabilities of β-cells are insufficient, which leads to the formation of hyperglycemia.

Diagnosis of gestational diabetes mellitus

To reduce the risk of complications for both the mother and the fetus, it is necessary to correctly diagnose and correct gestational diabetes mellitus.

The diagnosis is carried out in 2 stages:

• The first phase takes place when the pregnant woman first visits a doctor before 24 weeks of pregnancy.A woman undergoes one of the tests: donating venous blood on an empty stomach, glucose tolerance test or determination of glycated hemoglobin HbA1c.
• The second phase is carried out in pregnant women in whom carbohydrate metabolism disorders were not identified in the early stages.Diabetes mellitus is diagnosed by performing a glucose tolerance test with 75 g of glucose between 24 and 28 weeks of pregnancy.

Нормата на глюкозата на гладно при бременни жени е под 5,1 mmol/l. След един час по време на орален тест за глюкозен толеранс нормативните стойности са под <10,0 mmol/L, а след 2 часа над 7,8 mmol/L и под 8,5 mmol/L.

Pathological indicators of glucose in venous blood are the following values:

• on an empty stomach more than 7.0 mmol/l;
• glycated hemoglobin (HbA1) more than 6.5%;
• the glucose value is above 11.1 mmol/l (time of day and last meal do not matter).

These cases indicate a manifestation of gestational diabetes mellitus and require immediate insulin therapy.

Increased fasting values that do not meet the parameters of the diabetes manifest - above 5.1 mmol/l, but below 7.0 mmol/l, place the pregnant woman in a group with an increased risk of diabetes.Such women are recommended rational dietary therapy, dynamic control of glycemic levels and the condition of the fetus.

Symptomatic diabetes mellitus

This type is secondary and is caused by impaired glucose metabolism due to various diseases or drugs.These conditions include:

• diseases of the exocrine pancreas (pancreatitis, cancer, cystic fibrosis);
• medicinal diabetes mellitus - when taking glucocorticosteroids (they have a counterinsular effect, reduce the production of insulin in the body), phenytoin, estrogens (oral contraceptives).

Symptomatic diabetes mellitus can usually be treated by addressing the underlying cause of the diabetes (for example, changing or stopping the medication).

Why is hyperglycemia bad?

We have already understood that the absence or dysfunction of insulin leads to the accumulation of glucose in the blood.When the renal threshold is reached (>8.8 mmol/l – the value at which the kidneys begin to let glucose through when filtering the blood), glycosuria develops.Glucose is an osmotically active substance, so it binds water and leads to polyuria, loss of large amounts of water from the body and compensatory activation of the thirst center.

Polyuria (the separation of a large volume of urine in large portions) leads to dehydration of the body, a decrease in the volume of blood in the bloodstream, a decrease in blood pressure and hypoxia of the tissues located on the periphery.This is fraught with the risk of thromboembolism and the development of disseminated intravascular coagulation syndrome.

In addition, the pressure drop is less than 50 mm.rt.Art.leads to a delay in renal blood flow, to anuria (lack of urination) and the development of acute renal failure.

There is a peculiarity in the pathogenesis of type I diabetes mellitus - the absolute insulin deficiency leads to the activation of counterinsular hormones (insulin antagonists): T4, adrenaline, cortisol, somatotropic hormone, glucagon.

The following hormones improve all types of metabolism, leading to an even greater increase in glucose:

Lipolysis is the breakdown of fats, which leads to the formation of large amounts of free fatty acids (FFA), and from them - glucose.

FFA is an alternative source of energy in the body, serving as a basis for the formation of ketone bodies (for example, acetone).An increase in ketones in the blood and urine provokes vomiting, metabolic acidosis (decreased blood pH) and compensatory hyperventilation of the lungs (noisy, deep acidotic Kussmaul breathing occurs).The accumulation of ketones leads to one of the serious complications - ketoacidotic coma.

• Gluconeogenesis is a metabolic pathway by which glucose is synthesized from non-carbohydrate sources (amino acids, fatty acids).
• Glycogenolysis is the process of breaking down glycogen (storage of glucose in the liver).

Symptoms

We have considered the main links in the pathogenesis of diabetes mellitus, now we will outline the clinical symptoms by which this disease can be suspected:

• thirst (polydipsia) - associated with dehydration of the body;
• frequent urination (polyuria) - occurs due to the fact that glucose is osmotically active and binds water;
• increased appetite - occurs due to the fact that glucose does not enter the cells, a state of energy starvation is formed in them;
• dry skin, peeling, itching - these symptoms appear as a result of dehydration and dysfunction of the sweat and sebaceous glands;
• purulent skin diseases - arise as a result of a decrease in the resistance forces of the body;
• weakness, depressed mood.

Early complications

Early complications are acute conditions that are characterized by a rapid increase in clinical symptoms and require immediate medical intervention by a physician.

Early complications of type I diabetes

• Ketoacidotic coma is more often observed in the first type of diabetes mellitus.It is characterized by a sharp, "fruity" odor from the mouth, depression of consciousness, weakened reflexes, diarrhea, nausea, and ketoacidotic Kussmaul respiration.

Other complications are also characterized by suppression of consciousness, reflexes and decreased blood pressure:

• Hyperosmolar coma
• Lactic acidotic coma
• Hypoglycemic coma

The differential diagnosis of the type of coma is carried out with the help of biochemical analysis of blood, urine and the acid-base status of the blood.

Early complications of type II diabetes

• Hyperosmolar coma - seen more often
• Lactic acidotic coma
• Hypoglycemic coma

Late complications

These include:

• microangiopathies: retinopathy, nephropathy;
• macroangiopathies: coronary heart disease, angina pectoris, atherosclerosis, hypertension, chronic cerebral ischemia, acute cerebrovascular accident;
• neuropathies (polyradiculoneuropathy, radiculopathy, lumbar plexopathy);
• deposition of sorbitol in tissues (cataract);
• immunodeficiencies: purulent diseases, prolonged tissue healing);
• diabetic foot - pathological changes in the peripheral nervous system, arterial and microcirculatory channel, bone-joint apparatus of the foot with the development of ulcer-necrotic processes and gangrene.

Mechanisms of late complications

Late complications of diabetes are primarily related to blood vessel damage.Their main mechanism is the glycosylation of all protein structures of the body (vascular endothelium, basement membrane, vessels of nerve endings).

Glycosylated proteins:

• an increase in the permeability of the vascular wall and a violation of the rheological properties of the blood, which causes the development of thrombosis;
• promote the production of pro-inflammatory factors that damage small capillaries;
• blocks vasodilation;
• an increase in lipid peroxidation, which leads to the production of reactive oxygen species that damage tissues;
• contribute to the development of endothelial dysfunction and increase the risk of atherosclerosis.

As a result of these processes, the walls of small vessels become hard, inelastic and prone to rupture.The speed of blood flow in the small vessels slows down and the viscosity of the blood increases.

Cataract

Cataract is one of the frequent late complications of diabetes mellitus.

It is formed due to the fact that excess glucose enters alternative metabolic pathways.One of these pathways is the polyol oxidation pathway to sorbitol.Sorbitol is a compound that increases the osmotic pressure in the chambers of the eye and causes clouding of the lens.

Diabetic glomerulosclerosis

This nephropathy is accompanied by morphological changes in the capillaries and arterioles of the renal glomeruli, leading to their closure (occlusion), sclerotic changes, a progressive decrease in the filtration function of the kidneys and the development of chronic renal failure.

Diabetic neuropathy and retinopathy

Diabetic neuropathy is characterized by damage to the central and peripheral nervous system, which is clinically manifested by impaired sensitivity.

Diabetic retinopathy is characterized by damage to the capillaries, arterioles and venules of the retina with the development of microaneurysms, hemorrhages, exudative changes and the appearance of newly formed vessels.

Treatment of diabetes

Type 1 diabetes is treated with insulin.According to the duration of action, insulin is divided into:

• ultra-short action - used before every meal.Onset of action 5-15 minutes, duration 2-5 hours;
• short action - used before every meal.It starts working after 30 minutes and lasts 5-8 hours;
• average duration of action - begins to act after 1-2 hours, duration of action is 18-24 hours.Necessary for the main energy processes to take place;
• long-acting - begins to act after 1-2 hours, duration 18-36 hours.Necessary for the main energy processes to take place.

Doctors treat type II diabetes in 3 stages.

1st stage of treatment:

• in persons with normal body weight - dietary therapy (restriction of foods rich in carbohydrates);
• For people with excess body weight, obesity therapy is carried out: more active dietary therapy (strict restriction of the total caloric content of food, carbohydrates and animal fats), regular dosed (therapeutic) physical activity, a change in lifestyle, implying an increase in physical activity at home and during free time.

2nd stage of treatment:

• the use of drugs that stimulate β-cells: sulfonylurea derivatives, biguanides;
• the use of drugs that increase the sensitivity of insulin receptors in muscle and fat tissue: thiazolidinediones.

Stage 3 of treatment: insulin therapy.

Principles of emergency treatment

Ketoacidotic coma:

• insulin and glucose replacement therapy;
• restoration of fluid volume, electrolytes and blood pH.

Hyperosmolar coma:

• restoration of fluid volume and osmotic blood pressure by administration of hypotonic (0.45%) sodium chloride solution (2-3 liters);
• administration of electrolytes with short-acting insulin preparations in small doses (5-10 U/hour).

Advantages of treatment in the clinic

• Doctors will conduct a comprehensive diagnosis of the body for the presence of diabetes and its complications for treatment.
• We will choose an individual treatment program based on the latest clinical recommendations and many years of clinical experience of doctors.
• Doctors will provide a detailed consultation to the patient on what recommendations and rules should be followed by people with diabetes.