Insulin resistance (IR) is a reduction in the action of insulin in tissues and organs. With IL, the biological response to the physiological concentration of insulin is reduced. In some cases, when certain conditions are created, insulin loses its ability to manifest its influence under the influence of various factors, such as decreased physical activity, obesity, infections, injuries, stress, alcohol abuse, decreased blood supply to the muscles, increased levels of counter-hormone and other internal hormones. external factors.
Predisposition to IR is a historically established mechanism of adaptation of the human body to changes in external conditions in order to maintain energy balance and normal functioning of all organs and systems. In order to explain this genetic predisposition to IR, J. Nél in 1962 put forward the theory of the “lean genotype”. According to this theory, the human body accumulated fats and carbohydrates during times of well-being and abundance in nutrition, and during periods of food shortage, it maintained normoglycemia and more economically consumed energy by reducing glucose utilization in muscle tissue, increasing gluconeogenesis and lipogenesis. Thus, IR contributed to the survival of man in periods of famine. IR for a certain time keeps the body in a state between health and illness. Galen called this the “third” state of the organism. However, at present, in the conditions of hypodynamia and chronic overeating of fats, in the presence of other unfavorable factors, this mechanism becomes pathological and leads to the development of type 2 diabetes, hypertension, and atherosclerosis.
IR occurs as a result of a defect in insulin receptors, impaired glucose transport to the cell at the post-receptor level, and changes in the intracellular metabolism of glucose. These changes can be caused by a violation of the activity of the enzyme tyrosine kinase, the action of glucose transporter molecules, phosphorylation and dephosphorylation reactions, and enzymes involved in glycogen and lipid synthesis.
IR develops in skeletal muscle, adipose tissue and liver. Moreover, the decrease in insulin sensitivity is not the same in different tissues. With a decrease in insulin sensitivity in the cells of the liver and pancreas, its level in the blood significantly increases, while IR in the muscle tissue causes a significantly lower rise in insulin levels. However, with PCOS, insulin sensitivity in the androgen-producing structures of the ovaries and adrenal glands does not change, and the production of male sex hormones in response to hyperinsulinism increases, which aggravates the clinic hyperandrogenism. A decrease in the sensitivity of peripheral tissues to insulin on average by 50% is found with PCOS at least 2-3 times more often than in the general population.
In the 2003 Consensus, both the pathophysiological and clinical role of IR in PCOS was first stated. PCOS is characterized as ovarian dysfunction syndrome (irregular menstruation, persistent anovulation, infertility), the specific manifestations of which include not only hyperandrogenism, but also polycystic ovarian morphology.
In medicine, there has long been the opinion that hyperandrogenism leads to the development of hyperinsulinemia, based on the frequent detection of IR in patients with PCOS. However, the majority of facts testify in favor of the fact that it is hyperinsulinemia that leads to hyperandrogenism in women with PCOS. It has been shown that IR is maintained in patients with PCOS who undergo subtotal or total ovarian removal. Moreover, in women who have long applied GnRH agonists against the background of pronounced suppression of the level of androgens, AI is often noted. The administration of diazoxide, a drug that suppresses insulin secretion by the pancreas, causes a decrease in testosterone levels and an increase in the level of SSSH in patients with PCOS, obesity, and hyperinsulinemia. Intravenous administration of insulin to women with PCOS resulted in increased levels of circulating androstenedione and testosterone. Measures aimed at increasing insulin sensitivity (weight loss, fasting and low-calorie diet) were accompanied by a decrease in the level of androgens.
Some authors argued in favor of the primacy of hyperandrogenism, which in various ways can influence the transmission of the insulin signal to the receptor of the cell membrane in insulin-dependent tissues or distort its effects at the post-receptor level, in the cell. Other researchers obtained no less convincing data on the primary role of IR in steroid-synthesizing cells, which, through the mechanism of hyperinsulinism and through a local increase in production of insulin-like growth factors, increases the sensitivity of the adrenal glands to adrenocorticotropic hormone, and the gonad to LH, thereby triggering androgen hyperproduction. But today the point of view seems to be more convincing, according to which none of the participants of the ensemble “Hyperandrogenism Syndrome and Insulin Resistance + Hyperinsulinemia” (“SGA and IR + GI”) plays the first violin; they can mutually aggravate the course of competitive pathology, but they do not condition the emergence and development of each other.
The newest stage in the development of this rapidly progressing scientific concept was the receipt of a series of evidence linking two parallel current pathological processes into a single pathogenetic node of the manifestation of “MUH and IL + GI” in PCOS. The idea is that the structure of the cytochrome P450s17alpha (adrenal glands and gonads) and the composition of the insulin receptor (its B-subunit) include the amino acid of the series, the excessive phosphorylation of which serin-reininkinase (cAMP-dependent protein kinase C) causes two parallel processes: 1 \ increase in the activity of steroidogenic cytochrome, which triggers the manifestation of adrenal-ovarian hyperandrogenism and a cascade of subsequent reproductive abnormalities; 2 \ decrease in the sensitivity of the insulin receptor, leading to the formation of IR + GI and a wide range of endocrino-dysmetabolic complications.
The factors that increase the risk of IR syndrome include:
● diagnosed cardiovascular diseases, arterial hypertension, PCOS, non-alcoholic fatty hepatosis, or black acanthosis;
● burdened familial heredity for type 2 diabetes, hypertension, or cardiovascular disease;
● burdened history of gestational diabetes or the pathology of carbohydrate metabolism;
● “non-European” race;
● sedentary lifestyle;
● body mass index> 25 kg / m2 or abdominal circumference> 94 cm for men,> 80.5 cm for women;
● age> 40 years.
It should be noted that at the World Congress on Insulin Resistance (November 21-22, 2003; Los Angeles, USA), the recommendations of the American Association of Clinical Endocrinologists were considered, according to which insulin resistance in PCOS can be established regardless of other clinical and anamnestic risk factors and without hormonal analysis by the presence of at least 2 of the 4 following surrogate signs:
● triglycerides> 150 mg / dL;
● Reducing high-density lipoprotein cholesterol
● blood pressure> 130/85 mmHg. v .;
● glycemia (fasting 110-125 mg / dl, 120 min after glucose loading 140-200
mg / dl).
To assess the effect of androgens on IR, we examined 30 patients with F / M transsexualism who were on long-term androgen therapy – Omnadren-250 and Sustanon-250 1 every 1-3 weeks. The parameters of carbohydrate, lipid metabolism and the state of insulin secretion were investigated.
All examinations disruption of carbohydrate metabolism was detected in patients – glucose levels and immunoreactive insulin (and = 9) were within normal values. Against the background of ongoing androgen therapy, in 27 of 30 examined patients, indicators of total cholesterol and LDL were 5.4 5.3, 5.8 and 3.7 3, b, 3.9 mmol / l respectively, and exceeded the limits of normal values, at the same time, the levels of HDL and triglycerides were 1.30 0.99; 1.47 and 1.3 0.8; 1.5 mmol / l that is above normal values. However, when conducting a statistical analysis, the data of the increase were not statistically reliable, and therefore, the data obtained cannot indicate hyperlipidemic action of androgen therapy. All 30 patients had BP levels of 120/70 mm Hg. Art.
Thus, we did not reveal the negative effect of androgens on IR and carbohydrate metabolism. Moreover, abdominal obesity is characteristic of IR. In patients with therapy, the waist circumference decreased from 115 ± 12 to 95 ± 8 cm.
Thus, our examination of patients with F / M-transsexualism who are on androgen therapy for a long time showed no negative effect of androgens on carbohydrate metabolism and IR, and, moreover, a positive effect of androgens on adipose tissue, all patients showed a decrease in the abdominal obesity.