Insulin resistance - what is it? Metabolic insulin resistance syndrome

Different people are characterized by a different ability of insulin to stimulate the absorption of glucose. It is important to know that a person can have normal sensitivity to one or more effects of this compound and at the same time - absolute resistance to others. Next, we will analyze the concept of "insulin resistance": what it is, how it manifests itself.

General information

Before analyzing the concept of "insulin resistance", what it is and what signs it has, it should be said that this disorder occurs quite often. More than 50% of people with hypertension suffer from this pathology. Most often, insulin resistance (what it is, will be described below) is found in the elderly. But in a number of cases it is revealed in childhood. The insulin resistance syndrome often remains unrecognized before metabolic disturbances begin to occur. The risk group includes people with dyslipidemia or impaired glucose tolerance, obesity, hypertension.

Insulin resistance

What it is? What features does the violation have? The metabolic syndrome of insulin resistance is an incorrect response of the body to the action of one of the compounds. The concept is applicable to different biological effects. This, in particular, refers to the effect of insulin on protein and lipid metabolism, gene expression, vascular endothelial function. An abnormal response leads to an increase in the concentration of the compound in the blood relative to that necessary for the available volume of glucose. The insulin resistance syndrome is a combined disorder. It involves a change in glucose tolerance, type 2 diabetes, dyslipidemia, obesity. "Syndrome X" also suggests resistance to glucose uptake (insulin-dependent).

The mechanism of development

Completely it to study experts for today it was not possible. The disorders that lead to the development of insulin resistance can be noted at the following levels:

• Receptor. In this case, the condition is manifested by affinity or a decrease in the number of receptors.
• At the level of glucose transport. In this case, the number of GLUT4 molecules decreases.
• Pre-receptor. In this case, they talk about abnormal insulin.
• Postreceptive. In this case, there is a violation of phospholysis and a violation of signal transmission.

Anomalies of insulin molecules are quite rare and do not have clinical significance. Density of receptors can be lowered in patients in connection with negative feedback. It is caused by hyperinsulinemia. Often, patients have a moderate decline in the number of receptors. In this case, the level of feedback is not considered a criterion by which it is determined what degree insulin resistance has. The causes of the disorder are reduced by specialists to post-receptor impairment of signal transmission. The provoking factors, in particular, include:

• Smoking.
• Increase in the content of TNF-alpha.
• Decreased physical activity.
• Increase in the concentration of fatty, non-esterified acids.
• Age.

These are the main factors that most often can provoke insulin resistance. Treatment includes the use of:

• Diuretics of the thiazide group.
• Blockers of beta-adrenergic receptors.
• Nicotinic acid.
• Corticosteroids.

Increased insulin resistance

The effect on glucose metabolism occurs in adipose tissue, muscle and liver. Skeletal muscles metabolize about 80% of this compound. Muscles in this case act as an important source of insulin resistance. The capture of glucose into cells is carried out by means of a special transport protein GLUT4. When the receptor is activated to insulin, a series of phospholysis reactions is triggered. They eventually lead to the translocation of GLUT4 into the cell membrane from the cytosol. So glucose gets the opportunity to enter the cage. Insulin resistance (the norm will be indicated below) is caused by a decrease in the degree of translocation of GLUT4. At the same time there is a decrease in the use and capture of glucose by cells. Along with this, in addition to facilitating glucose uptake in peripheral tissues, hyperinsulinemia suppresses the production of glucose by the liver. With type 2 diabetes, it resumes.

Obesity

It is combined with insulin resistance quite often. When the patient exceeds the weight by 35-40%, the sensitivity decreases by 40%. The adipose tissue in the anterior abdominal wall has a higher metabolic activity than the one below. During medical observations, it was found that the increased release of fatty acids from the abdominal fibers into the portal bloodstream provokes the production of triglycerides by the liver.

Clinical signs

Insulin resistance, the symptoms of which are associated with a metabolic disorder primarily, can be suspected in patients with abdominal obesity, gestational diabetes, a family history of type 2 diabetes, dyslipidemia and hypertension. In the risk group, women with PCOS (polycystic ovary). Due to the fact that obesity is a marker of insulin resistance, it is necessary to evaluate the nature of the distribution of fatty tissue. Its location can be on the gynecoid - in the lower part of the trunk, or in the android type - in the anterior wall of the peritoneum. Accumulation in the upper half of the body is characterized by a more significant prognostic factor of insulin resistance, altered glucose tolerance and diabetes than obesity in the lower areas. To determine the amount of fat abdominal tissue, you can use the following method: determine the ratio of waist, hip and BMI. At rates of 0.8 for women and 0.1 for men and a BMI of more than 27, they diagnose abdominal obesity and insulin resistance. Symptoms of pathology are manifested externally. In particular, the skin shows wrinkled, rough hyperpigmented areas. Most often they appear in the armpits, on the elbows, under the mammary glands. Analysis for insulin resistance is a calculation by the formula. HOMA-IR is calculated as follows: fasting insulin (μU / ml) x fasting glucose (mmol / l). The result is divided into 22.5. The result is an index of insulin resistance. The norm is <2.77. In the event of a deviation in the direction of increase, a sensitivity disorder can be diagnosed.

Violations of other systems: atherosclerosis of blood vessels

Today, there is no single explanation for the mechanism of the effect of insulin resistance on the damage to the cardiovascular system. There may be a direct effect on atherogenesis. It is caused by the ability of insulin to stimulate the synthesis of lipids and the proliferation of smooth muscle components in the vessel wall. Together with this, atherosclerosis can be caused by concomitant metabolic disturbances. For example, it can be hypertension, dyslipidemia, changes in glucose tolerance. In the pathogenesis of the disease, the disturbed function of the vascular endothelium is of particular importance. His task is to maintain the tone of the blood channels due to the secretion of mediators of vasodilation and vasoconstriction. In a normal state, insulin provokes relaxation of the smooth muscle fibers of the vascular wall upon the release of nitric oxide (2). At the same time, his ability to increase endothelium-dependent vasodilation varies significantly in patients with obesity. The same is true for patients with insulin resistance. With the development of the inability of the coronary arteries to respond to normal stimuli and expand it can be said about the first stage of microcirculation disturbance - microangiopathy. This pathological condition is noted in the majority of patients with diabetes mellitus (diabetes mellitus).

Insulin resistance can provoke atherosclerosis through abnormalities in the fibrinolysis process. IAP-1 (inhibitor of the plasminogen activator) is in a high concentration in patients with diabetes and obesity without diabetes. Synthesis of IAP-1 is stimulated by proinsulin and insulin. The level of fibrinogen and other procoagulant factors is also increased.

Changed glucose tolerance and type 2 diabetes

Insulin resistance is a precursor to the clinical manifestation of diabetes. Beta cells in the pancreas respond to the decrease in glucose concentration. Reduction of concentration is due to increased production of insulin, which, in turn, leads to relative hyperinsulinemia. Euglycemia can persist in patients as long as beta cells will be able to maintain a fairly high level of insulin in the plasma to overcome resistance. Ultimately, this ability is lost, and the concentration of glucose increases significantly. The key factor that is responsible for fasting hyperglycemia in the background of diabetes is insulin resistance of the liver. A healthy response is to lower the production of glucose. With insulin resistance, this reaction is lost. As a result, the liver continues to overproduce glucose, which leads to fasting hyperglycaemia. With the loss of the ability of beta cells to provide hypersecretion of insulin, there is a transition from insulin resistance to hyperinsulinemia to altered glucose tolerance. Subsequently, the condition is transformed into clinical diabetes and hyperglycemia.

Hypertension

There are several mechanisms that determine its development against the background of insulin resistance. As observations show, the weakening of vasodilation and the activation of vasoconstriction may contribute to an increase in vascular resistance. Insulin promotes stimulation of the nervous (sympathetic) system. This results in an increase in the concentration of noradrenaline in the plasma. In patients with insulin resistance, the response to angiotensin was increased. In addition, the mechanisms of vasodilation can be disrupted. In a state of norm, the introduction of insulin provokes relaxation of the muscular vascular wall. Vasodilation in this case is mediated by the release / production of nitric oxide from the endothelium. In patients with insulin resistance, the endothelial function is impaired. This leads to a decrease in vasodilatation by 40-50%.

Dyslipidemia

With insulin resistance, the normal suppression of the yield of fatty free acids after eating from adipose tissue is disrupted. Increased concentration forms a substrate for enhanced triglyceride synthesis. This is an important stage in the production of VLDL. With hyperinsulinemia, the activity of an important enzyme, lipoprotein lipase, is reduced. Among the qualitative changes in the LDL spectrum against the background of type 2 diabetes and insulin resistance, it should be noted the increased oxidation of LDL particles. More susceptible to this process are glycated apolipoproteins.

Therapeutic events

Increases in insulin sensitivity can be achieved in several ways. Of particular importance is weight loss and physical activity. Nutritional regimen is also important for people who are diagnosed with insulin resistance. The diet contributes to the stabilization of the condition for several days. Increased sensitivity will be further facilitated by weight loss. For people who have insulin resistance, treatment consists of several stages. Stabilization of diet and physical activity is considered the first stage of therapy. For people who have insulin resistance, the diet should be low-calorie. Moderate reduction in body weight (by 5-10 kilograms) often contributes to improving control over glucose levels. Calories for 80-90% are distributed between carbohydrates and fats, 10-20% are proteins.

Medications

Means "Metamorfin" refers to the medicines of the biguanide group. The drug improves peripheral and hepatic sensitivity to insulin. In this case, the agent has no effect on its secretion. In the absence of insulin, the drug "Metamorfin" is ineffective. The drug "Troglitazone" is the first medication of the group of thiazolidine-adiones, which is approved for use in the USA. The drug enhances the transport of glucose. This is probably due to the activation of the PPAR gamma receptor. And the account of this increases the expression of GLUT4, which, in turn, leads to an increase in insulin-induced glucose uptake. For patients who have insulin resistance, treatment can be prescribed and combined. The above agents can be used in combination with sulfonylurea, and sometimes with each other to obtain a synergistic effect on the glucose level in the plasma and other disorders. The drug "Metamorfin" in combination with sulfonylurea increases secretion and sensitivity to insulin. At the same time, the glucose level decreases after eating and on an empty stomach. In patients who were prescribed combined treatment, hypoglycemia was more common.