Hypoglycemic syndrome: causes, diagnosis, treatment. Part 1

Glucose is the most important component of human metabolism. Being a source of energy for the life of cells and, in particular, brain cells, it performs plastic functions in the body.

There is practically no free glucose inside the cells. In cells, glucose accumulates in the form of glycogen. During oxidation, it turns into pyruvate and lactate (anaerobic way) or carbon dioxide (aerobic way), into fatty acids in the form of triglycerides. Glucose is an integral part of the nucleotide molecule and nucleic acid. Glucose is necessary for the synthesis of certain amino acids, the synthesis and oxidation of lipids, polysaccharides.

The concentration of glucose in human blood is maintained in a relatively narrow range – 2.8–7.8 mmol / l, regardless of gender and age, despite the large differences in nutrition and physical activity (postprandial hyperglycemia – an increase in blood glucose after eating stress factors and its reduction in 3-4 hours after eating and exercise). This constancy provides brain tissue with a sufficient amount of glucose, the only metabolic fuel they can use under normal conditions.

Depending on the method of glucose intake, all organs and tissues of the body are divided into insulin-dependent: glucose enters these organs and tissues only in the presence of insulin (adipose tissue, muscles, bone, connective tissue); insulin-independent organs: glucose enters them along a concentration gradient (brain, eyes, adrenal glands, gonads); relatively insulin-independent organs: free fatty acids (heart, liver, kidneys) are used as nutrients in the tissues of these organs.

Maintaining glucose within certain limits is an important task of a complex system of hormonal factors. Each time a meal is taken, the glucose level rises and the insulin level rises in parallel. Insulin promotes the entry of glucose into the cells, which not only prevents a significant increase in its concentration in the blood, but also provides glucose intracellular metabolism.

The insulin concentration during the fasting period fluctuates around 10 mC / ml and rises to 100 mC / ml after a normal meal, reaching maximum values ​​30–45 minutes after a meal. This effect is mediated through ATP-sensitive potassium channels, which consist of the SUR-1 and Kir 6.2 protein subunits. Glucose entering the beta-cell with the participation of the enzyme glucokinase undergoes transformation to form ATP. Increased ATP contributes to the closure of potassium channels. Potassium concentration in the cytosol of the cell increases. In the same way, glutamate metabolites act on these channels through oxidation by the enzyme glutamate decarboxylase. The increase in potassium in the cell causes the opening of calcium channels, and calcium rushes into the cell. Calcium promotes the transfer of secretory granules to the periphery of the cell and the subsequent release of insulin into the intercellular space, and then into the blood. Insulin food secretagens are amino acids (leucine, valine, etc.). Their effect is enhanced by small intestinal hormones (gastric inhibitory polypeptide, secretin). Other substances stimulate its secretion (sulfonylurea preparations, beta-adrenoreceptor agonists).

Glucose enters the bloodstream in different ways. After a meal, for 2-3 hours, exogenous carbohydrates are the main source of glycemia. A person engaged in physical labor should contain 400–500 g of glucose in food. Between meals, most of the glucose in the circulating blood is supplied by glycogenolysis (accumulated glycogen in the liver is destroyed to glucose, and glycogen in the muscles to lactate and pyruvate). When fasting and depletion of glycogen stores, gluconeogenesis becomes a source of glucose in the blood (the formation of glucose from non-carbohydrate substrates: lactate, pyruvate, glycerin, alanine).

Most food carbohydrates are polysaccharides and consist mainly of starches; the smaller part contains lactose (milk sugar) and sucrose. Digestion of starches begins in the oral cavity with ptyalin saliva, which continues its hydrolytic effect in the stomach, until the pH of the medium becomes too low. In the small intestine, pancreatic amylase breaks down starches into maltose and other glucose polymers. The enzymes lactase, sucrase and alpha dextrinase, which are secreted by the epithelial cells of the brush border of the small intestine, break down all disaccharides into glucose, galactose and fructose. Glucose, which constitutes more than 80% of the final carbohydrate digestion product, is immediately absorbed and enters the portal blood flow.

The glucagon, synthesized by the A-cells of the islets of Langerhans, changes the availability of substrates in the intervals between meals. By stimulating glycogenolysis, it provides a sufficient release of glucose from the liver in the early period of time after meals. As glycogen depletes in the liver, glucagon along with cortisol stimulate gluconeogenesis and ensure the maintenance of normal fasting blood glucose.

During an overnight fast, glucose is synthesized exclusively in the liver and most of it (80%) consumes the brain. In a state of physiological rest, the glucose exchange rate is approximately 2 mg / kg / min. People weighing 70 kg need 95–105 g of glucose for a 12-hour interval between dinner and breakfast. Glycogenolysis is responsible for about 75% of the nightly production of glucose in the liver; the rest is gluconeogenesis. The main substrates for gluconeogenesis are lactate, pyruvate and amino acids, especially alanine and glycerin. When the fasting period is delayed and the insulin content falls, gluconeogenesis in the liver becomes the only source for maintaining euglycemia, since all the glycogen stores in the liver are already used up. At the same time, fatty acids are metabolized from adipose tissue to provide a source of energy for muscle activity and available glucose for the central nervous system. Fatty acids are oxidized in the liver to form ketone bodies – acetoacetate and beta-hydroxybutyrate.

If fasting continues for days and weeks, other homeostatic mechanisms are activated that ensure the preservation of the protein structure of the body, slowing down gluconeogenesis and switching the brain to the utilization of ketone molecules, acetoacetate and beta-hydroxybutyrate. A signal for the use of ketones is an increase in their concentration in arterial blood. With prolonged fasting and severe diabetes, extremely low concentrations of insulin are observed in the blood.

Hypoglycemia and hypoglycemic states

Hypoglycemia is considered to be a decrease in the concentration of glucose in the blood below 2.5-2.8 mmol / l in men and less than 1.9-2.2 mmol / l in women.

In healthy people, the inhibition of endogenous insulin secretion after absorption of glucose into the blood begins at a concentration of 4.2–4 mmol / l, with a further decrease in it, it is accompanied by the release of counterinsular hormones. After 3-5 hours after a meal, the amount of absorbed glucose from the intestines decreases progressively and the body switches to endogenous glucose production (glycogenolysis, gluconeogenesis, lipolysis). During this transition, functional hypoglycemia may develop: early – in the first 1.5–3 hours and late – in 3–5 hours. “Hunger” hypoglycemia is not associated with food intake and develops on an empty stomach or 5 hours after it is taken. There is no strong correlation between the level of glucose in the blood and the clinical symptoms of hypoglycemia.

Manifestations of hypoglycemia

Hypoglycemia is more a clinical concept than a laboratory one, whose symptoms disappear after normalization of glucose in the blood. The development of symptoms of hypoglycemia is affected by a rapid decrease in blood glucose. This is evidenced by the factors of rapid reduction of high glycemia in patients with diabetes. The appearance of clinical symptoms of hypoglycemia is observed in these patients with high rates of glycemia with active insulin therapy.

Symptoms of hypoglycemia differ in polymorphism and nonspecificity. For hypoglycemic disease, the Whipple triad is pathohomonic:

  • the onset of hypoglycemia after prolonged fasting or physical exertion;
  • decrease in blood sugar during an attack below 1.7 mmol / l in children under two years of age, below 2.2 mmol / l – over two years;
  • relief of a hypoglycemic attack by intravenous administration of glucose or oral administration of glucose solutions.

Symptoms of hypoglycemia are due to two factors:

  • stimulation of the sympaticoadrenal system, resulting in increased secretion of catecholamines;
  • deficiency in the supply of glucose in the brain (neuroglycemia), which is equivalent to a decrease in oxygen consumption by nerve cells.

Symptoms such as excessive sweating, constant hunger, tingling of the lips and fingers, pallor, palpitations, small tremors, muscle weakness and fatigue, are caused by the excitation of the sympathetic-adrenal system. These symptoms are early harbingers of an attack of hypoglycemia.

Neuroglycemic symptoms are manifested by headache, yawning, inability to concentrate, fatigue, inadequate behavior, hallucinations. Sometimes there are also mental symptoms in the form of depression and irritability, drowsiness during the day and sleeplessness at night. Due to the variety of symptoms of hypoglycemia, among which the anxiety reaction often dominates, many patients are mistakenly diagnosed with neurosis or depression.

A long and deep hypoglycemic coma can cause swelling and swelling of the brain with subsequent irreversible damage to the central nervous system. Frequent bouts of hypoglycemia lead to personality changes in adults, reduced intelligence in children. The difference between the symptoms of hypoglycemia and the real neurological conditions is the positive effect of eating, the abundance of symptoms that do not fit into the clinic of a neurological disease.

The presence of pronounced neuropsychiatric disorders and insufficient awareness of doctors about hypoglycemic conditions often lead to the fact that, as a result of diagnostic errors, patients with organic hyperinsulinism are treated for a long time and unsuccessfully under a variety of diagnoses. Erroneous diagnoses are made in 3/4 of patients with insulinoma (epilepsy is diagnosed in 34% of cases, a brain tumor in 15%, vegetative dystonia in 11%, diencephalic syndrome in 9%, psychosis, neurasthenia in 3%).

Most of the symptoms of hypoglycemia are due to insufficient supply of glucose to the central nervous system. This leads to a rapid increase in adrenaline, norepinephrine, cortisol, growth hormone, glucagon.

Episodic hypoglycemic states can be compensated by the triggering of contrainsular mechanisms or food intake. In case this is not enough, a fainting state or even coma develops.

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