The problem of pathogenesis, clinical manifestations and approaches to the therapy of metabolic syndrome (MS) attracts the attention of many endocrinologists.
This is explained by the fact that one of the most important components of this syndrome is a violation of carbohydrate metabolism, which can manifest as type 2 diabetes, or a violation of glucose tolerance (latent diabetes mellitus). Very often in clinical practice, when providing medical care to patients suffering from type 2 diabetes, the endocrinologist calls attention to the identification and conduct of drug correction of other manifestations of metabolic syndrome (MS) – arterial hypertension, dyslipidemia, etc.
His views on this problem were shared by the head of the Department of Diabetology of the National Medical Academy of Postgraduate Education named after P.L. Shupika, Honored Worker of Science and Technology of Ukraine, Doctor of Medical Sciences, Professor Mankovsky Boris Nikitich.
In recent years, the problem of metabolic syndrome is extremely topical. Most doctors already know about the main criteria on the basis of which this state is determined. First of all, cardiologists and endocrinologists are aware of these criteria and methods of treatment of patients with metabolic syndrome. In your opinion, how can one avoid and with what it is necessary to start treatment of the metabolic syndrome?
Indeed, in recent years, the attention of clinicians and scientists has been attracted by mechanisms of development and approaches to the therapy of the so-called metabolic syndrome – a complex of clinical, pathophysiological and laboratory disorders, many of which develop in parallel. It should be noted that the presence of these deviations occurs more often than could be expected from the theory of probability.
The manifestations of this syndrome include the following pathologies: type 2 diabetes mellitus (or impaired glucose tolerance), insulin resistance, arterial hypertension (AH), obesity (by android type with predominant deposition of adipose tissue in the anterior abdominal region Walls), dyslipidemia (increased triglyceride content, lowering of high-density lipoprotein cholesterol in blood plasma), prothrombotic shifts in blood coagulation properties (increase in tissue inhibitor activity th plasminogen-1, von Willebrand factor, fibrinogen), endothelial dysfunction (including microalbuminuria), increased levels of uric acid in blood plasma, liver, fatty liver (non-alcoholic steatogepatoz), activation of general inflammation. Thus, the combination of the listed characteristics in one person allowed us to talk about the existence of a common, so-called metabolic syndrome, which leads to the development of such changes.
What is the important concept of the metabolic syndrome?
First, the concept of metabolic syndrome (MS) stimulates physicians to find other nosological units in the patient. So, if the patient has obesity and hypertension, you should check the blood glucose level and, possibly, make a test for glucose tolerance; If diabetes and obesity – you should think about AG. So, if a person, often develop different diseases at the same time, should (if possible) quickly diagnose them.
Secondly, in people with metabolic syndrome, the risk of developing cardiovascular diseases and high cardiovascular risk (CVR) are increased. Whether the increase in CWR is caused by the components of the metabolic syndrome or whether there is a certain “independent contribution” of the metabolic syndrome as such – the question is controversial, there is no answer to it yet. In any case, it must be remembered that patients with metabolic syndrome are patients with high CVR.
How to diagnose a metabolic syndrome?
In the diagnosis of metabolic syndrome, the criteria proposed in the United States in 2001 (ATP III) and the principles approved by the World Federation of Diabetes Mellitus (IDF) in 2005 are most often used. According to the proposals of ATP III for the diagnosis of MS, it is necessary to identify three or more of the following symptoms:
- Abdominal obesity (abdominal circumference exceeds 102 cm in men and 88 cm in women);
- An increase in triglyceride levels in the blood plasma of more than 150 mg / dl (1.69 mmol / l);
- Reduction in high-density lipoprotein cholesterol: in men less than 40 mg / dl (1.03 mmol / L), in women less than 50 mg / dL (1.29 mmol / L);
- Arterial hypertension (increase in blood pressure above 130/85 mm Hg);
- Hyperglycemia on an empty stomach is more than 110 mg / dl (5.6 mmol / l).
The approach proposed by ATP III is very convenient and easy to apply in clinical practice (even in normal, non-specialized laboratories).
According to the consensus proposed by IDF, the presence of abdominal obesity (central, android, called “obesity” by the type of apple) is mandatory for the diagnosis of the metabolic syndrome.
What is the cause of the metabolic syndrome?
Today there are two opinions about the causes of metabolic syndrome (MS). Some researchers suggest that obesity (excess body weight) leads to the development of metabolic syndrome. According to this opinion, overweight is not only a cosmetic defect, but also the accumulation of adipose tissue (and fat tissue, as shown by recent studies, is very metabolically active). Thus, adipocytes visceral fat produce a number of biologically active substances (leptin, free fatty acid, TNF-α, insulin-like growth factor, plasminogen activator inhibitor, angiotensinogen, angiotensin II, interleukins, prostaglandins, estrogens) that promote the previously described manifestations of the metabolic syndrome . Proceeding from the foregoing, obesity is not only the most important component of the metabolic syndrome, but also, apparently, a significant etiologic factor of this pathology.
Other researchers are inclined to believe that the pathogenesis of the metabolic syndrome is based on a decrease in the sensitivity of tissues to the action of insulin, the so-called insulin resistance. insulin interaction problem with the target tissues, mechanisms of insulin resistance in the background of both normal and abnormal carbohydrate metabolism attracted special attention of endocrinologists.
The question of whether insulin resistance is secondary to obesity (as most people think) or insulin resistance can be on its own – remains unresolved until now. In any case, obesity is an important component of the metabolic syndrome.
In order to get rid of or reduce the risk of metabolic syndrome (MS), it is necessary to motivate patients to lose weight and, thus, to correct the metabolic syndrome. Indeed, the only universal method of treating metabolic syndrome is a lifestyle modification (reduction in body weight, increase physical activity). If patients followed the recommendations of doctors, they would not have to prescribe medication (or it would have to be prescribed less often than it is now prescribed). Therefore, weight loss (weight loss) is the “cornerstone” of therapy for the metabolic syndrome.
It turns out that it is worth the patient with any pathology, when it comes to the metabolic syndrome, to do correction of his body weight – it becomes possible to avoid complications of the underlying disease, and the need for a diagnosis of “metabolic syndrome” will go away on its own.
To make my answer more clear, I want to cite the results of the ORLICARDIA study (The ORLIstat and CARDIOVATIC risk profile in patients with metabolic syndrome and type 2 DIAbetes (ORLICARDIA) study), conducted in 2003. The study showed a decrease in body weight (MT) and waist circumference (RT) by 2.5 kg and 2.3 cm, respectively, when used as a low-calorie reduced diet therapy. Against the background of taking Orlistat (“Xenical“) in a dose of 120 mg 3 times a day after meals, a decrease in MT and RT by 6 kg and 7.2 cm, respectively, was observed together with a hypocaloric diet (GCD).
Thus, patients who received orlistat, lost weight (reduced body weight) by 6% against 2.5% in patients who adhered to only a hypocaloric diet. This decrease in body weight led to the fact that 35% of people in this group could not diagnose the metabolic syndrome because they not only decreased their body weight, but also left other signs of metabolic syndrome (blood pressure decreased, lipid parameters improved Exchange, blood glucose levels, etc.), which allowed to make a diagnosis.
How to achieve such a reduction in body weight?
To effectively reduce weight, an integrated approach is required. First of all, it is a moderate hypocaloric diet with a deficiency of 500-600 calories per day, a reduced fat content in food up to 20-30%, a hypolipidemic diet (the permissible content of saturated fats should not exceed 10%), increased physical activity that contributes to more Expressed by a decrease in body weight and allows you to keep it at the reached level. Unfortunately, the hypocaloric diet itself and in itself the expansion of physical activity does not always help to actually reduce body weight. Therefore, doctors would like to have in the arsenal of drugs that will help patients reduce body weight. In this regard, there is a big problem, because, unfortunately, the drugs, which were placed high hopes for weight loss, were unsafe. Let me give you some examples.
The drug Rimonobant, which was eagerly awaited by the pharmaceutical market in Europe, including our market, did not come out, since its purpose was associated with an increased risk of suicidal reactions. Another drug that was already on the market and actively used, including in our country, is Sibutramine. This drug was recently withdrawn from the pharmaceutical market, as a result of a large multicenter study, SCOUT (Sibutramine Cardiovascular Outcomes Data), in which the task was to study the possible reduction in cardiovascular risk (CVR) by prescribing this drug, showed the opposite (CWR, not only Decreased, but on the contrary – increased).
Thus, to date, of drugs that reduce body weight, we have at our disposal only one drug with proven efficacy.
What kind of preparation is it?
This drug orlistat (Xenical), which I mentioned earlier.
What is the mechanism of action of this drug?
Xenical blocks 30% of pancreatic lipases – enzymes that break down fats in the lumen of the intestine. Accordingly, if enzymes do not split 30% of fats eaten by a person, they are not absorbed (only simple molecules can absorb in the intestine). This means that a person learned 30% less fat. This is the mechanism of losing weight.
It is very important to note that this drug is not a systemic action, since it is not absorbed in the lumen of the intestine and does not enter the blood.
What is the effectiveness of Xenical?
I have already talked about reducing the manifestations of the metabolic syndrome (MS) against the backdrop of using Xenical. Due to what? In the previous study, it was also shown that patients who used Xenical lost weight more effectively than those who only observed the diet. For example, according to the study, a pronounced effect on body weight (a decrease of 5%) was noted in 87% of patients receiving Xenical, and in 50% there was a 10% decrease in weight.
Talking about losing weight, we can not and should not strive to achieve an ideal body weight. Very good is considered a decrease in body weight by 5%, excellent – by 10%.
Recently completed a four-year international double-blind study of Xendos involving 3305 patients with obesity. His results showed that the use of Xenical in a dose of 120 mg 3 times a day compared with placebo significantly reduces body weight (p <0.001) and significantly reduces the risk of developing type 2 diabetes mellitus (a decrease of 52% in the orlistat group according to Compared with 34% in the placebo group, p <0.0001). The latter effect is especially pronounced in patients with initial glucose tolerance impairment.
Thus, the drug really allows you to reduce body weight, but again – against a diet. This drug, like any other, should work against the backdrop of the patient’s desire, diet and expansion of physical activity.
What are the side effects of the drug?
As already noted, Xenical is a non-systemic drug that is not absorbed in the intestine. The side effect is that 30% of the fats do not split and remain in the lumen of the intestine, thus stimulating the bowel motility and causing a loosening of the stool. However, eventually these side effects go away, and most patients tolerate the drug safely.
It should be warned that the drug should be prescribed only when the diet contains fatty foods, otherwise there will be no effect from it, since there is no substratum of its effect. Naturally, this does not mean that you should increase the amount of fatty food when taking this drug. It should be emphasized that if a patient plans to eat only carbohydrate or protein foods (such as fruit), it is not advisable to take the drug at the same time with such a meal.
Orlistat should be prescribed on the recommendation of a doctor, since uncontrolled intake in large doses can lead to damage to the liver tissue.
Thus, summing up all the above, I want to note that metabolic syndrome is a global problem, as it is noted in about a quarter of the world’s people and is a complex of various pathological conditions. For successful correction and treatment, first of all, you need to change your lifestyle and achieve weight loss. Practically this can be achieved with the use of drugs, the effectiveness and safety of which is registered and confirmed in the world and domestic clinical practice.