Interest in the metabolic syndrome in recent years has increased dramatically from various specialists, due to the discovery of subtle molecular mechanisms of interaction of insulin and other factors in various target tissues. G.M. Reaven  associates the development of clinical signs of this complex syndrome with insulin resistance, so many suggest the name of the disease – “insulin resistance syndrome”. Indeed, numerous studies [1, 2, 4] proved the presence of hyperinsulinemia, as a compensatory state of the organism in response to insulin resistance. Insulin resistance is the disturbed sensitivity of peripheral tissues (liver, muscles, adipose tissue, etc.) to insulin. Insulin resistance is an inherited condition. The genetic predisposition to insulin resistance is associated with a gene mutation:
- Insulin receptor substrate I (insulin receptor tyrosine kinase),
- Glycogen synthase,
- Glucose transporters II or IV,
- Hexokinase II,
- Protein binding the FFA (FABP-II).
At the same time, a hypothesis is advanced according to which insulin resistance is not the cause of the development of this syndrome, but also its one component . The author came to this conclusion on the basis of studying the prevalence of components of the metabolic syndrome in different ethnic groups (black, white population of the USA and Americans of Mexican origin). Analysis of the data obtained suggested the presence of a different genetic factor in the etiology of the metabolic syndrome. Such a hypothetical factor was called “factor Z”, which, interacting with insulin sensitive tissues, endothelium, regulating system of arterial pressure and lipid and lipoprotein exchange, causes, respectively, insulin resistance, atherosclerosis, arterial hypertension, dyslipidemia.
The WHO working group constituting the components of the metabolic syndrome recognized the following symptom complex (1998): visceral (abdominal) obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance (STH) or type 2 diabetes, arterial hypertension, dyslipidemia, hemostasis disorders, hyperuricemia, microalbuminemia.
The clinical sign of insulin resistance is considered to be the abdominal type of obesity, in which the ratio of the waist to the hip volume exceeds 0.95 in men and 0.85 in women.
The developed therapeutic approach to the treatment of the metabolic syndrome has not been found to date. As a rule, antidiabetic therapy occupies a central place in treatment activities. In the fight against insulin resistance in clinical practice, metformin is widely used in an individually selected dosage. When metformin is ineffective, its combination with sulfonylurea preparations, a-glycosidase inhibitors or nonsulfonylurea secretinogens is used. In complex therapy, hypolipidemic and antihypertensive drugs are recommended, along with diet therapy. However, the fact of the close dependence of insulin resistance on the degree of obesity is known. According to Amos et al. , insulin resistance is associated, more likely, with obesity than with diabetes mellitus. Therefore, an urgent requirement is weight reduction in patients with metabolic syndrome. A decrease in body weight of only 5% of the initial weight leads to improved glycemic control, lower blood pressure, improved lipid profile, and a 20% reduction in the risk of premature death.
Given the presence of insulin resistance and, as a consequence, hyperinsulinemia – antilipolytic factor, in the metabolic syndrome, it is natural to assume the difficulty of reducing weight in this category of patients. The presence of arterial hypertension in these patients is an obstacle for the appointment of anorektiky, oppressing appetite by inhibiting the reverse neuronal capture of catecholamines from the intersynaptic gap.
Among the drugs that contribute to weight loss, a special place belongs to orlistat (Xenical Online) – a drug that does not have a systemic effect, acting inhibitory to the gastrointestinal lipase. Xenical has a high lipophilicity and is readily soluble in fats. Due to this, getting into the body with food containing fats, Xenical mingles with drops of fat in the stomach, blocks the active center of the lipase molecule, not allowing the enzyme to split fats (triglycerides). Unclosed triglycerides can not enter the blood and are excreted with feces.
Suppressing the activity of gastrointestinal lipases reduces the absorption of fats, which creates a deficit of energy and helps to reduce body weight. Simultaneously, the number of free fatty acids and monoglycerides in the lumen of the gut decreases, which reduces the solubility and subsequent absorption of cholesterol, contributing to the reduction of hypercholesterolemia. In a placebo-controlled study of 52 weeks duration in patients with diabetes mellitus and visceral obesity (metabolic syndrome), when Xenical was used at a dose of 120 mg 3 times a day, the body weight was reduced by 6.2% from the baseline (Figure 1), at 4.3% In the placebo group (p <0.001). The use of Xenical in patients with metabolic syndrome contributes to the compensation of carbohydrate metabolism (by the end of 1 year of treatment a good SD compensation was achieved in 67% of patients, compared with 31% on a diet). A similar trend was observed and at the end of 2 years of treatment (Figure 2). At the same time, the daily requirement for oral hypoglycemic drugs in patients receiving Xenical decreased by 23%, compared with 9% in patients on a diet (Figure 3). Treatment with Xenical was accompanied by a decrease in insulin levels by 18% (8.7% on a diet). In cases of a metabolic syndrome with impaired tolerance to carbohydrates, a two-year therapy with Xenical reduced the risk of NTG and type 2 diabetes (Fig. 4). The study of the lipid profile showed a significant decrease in the level of cholesterol and lipoprotein compared to placebo (Table 1). After 1 year of Xenical therapy, the diastolic blood pressure decreased by 10.6 mm. Gt; Art. (3.6 mm Hg in the placebo group). The waist circumference (OT) after two years of therapy decreased by 5.8 cm (in the group receiving a placebo – 2.9 cm).
Thus, Xenical is an effective drug for treating patients with metabolic syndrome, and a decrease in hyperinsulinemia indicates a pathogenetically justified approach to the treatment of insulin resistance. Data from questionnaires of patients at the 52nd and 104th weeks of treatment indicated that patients receiving Xenical were:
- More satisfied with treatment
- More satisfied with the dynamics of their state
- Less concerned about the fact of being overweight.
In 31% of patients taking Xenical, excessive fat release was observed, and the rate of defecation increased in 20.4% of cases. However, only 0.3% of patients discontinued treatment for this reason. Oily discharge from the rectum was noted in 17.5% of patients at 1.2% in the placebo group. It should be noted that these side effects were the result of excessive consumption of fat and, of course, indicate a high effectiveness of the drug. Xenical should be used with a moderately hypocaloric diet containing 30% of calories in the form of fats. In this case, discomfort from the intestine, as a rule, is not observed.