Savchenko L. G., Lavrenko A. V., Gerasimenko N. D., Rasіn M. S., Kaydashev І. P.

CONTENTS

Scentific article

The twentieth century has confronted humanity new problems: chronic stress, overeating and hypokinesia. The body of many people responded to this with chronic systemic low grade inflammation (LGI), obesity and insulin resistance (IR). IP leads to hyperinsulinemia, hyperglycemia, dyslipidemia and endothelial dysfunction – basis to the development of atherosclerosis, hypertension and type 2 diabetes (DM2). It is clear that the most rational prophylaxis of diseases which are endemic – a rational diet and physical exercise. However, for various reasons, many people cannot use these methods. In this case, the aid of pharmacological agents that prevent the development of LGI and IR. There are only two groups of funds directly inhibit LGI and overcome IP: metformin (MF) and glitazones. In the pathogenetic chain of these diseases important place belongs to activation of the renin-angiotensin-aldosterone system. In this paper, we tried to assess the possibility of secondary prevention of coronary heart disease (CHD) and DM2 by including in the complex therapy of metformin and ramipril – angiotensin converting enzyme blocker of new generation. Materials and methods. We examined 24 men aged 57,2 ± 2 years of age who had clinical signs of coronary heart disease, obesity and DM2 (7 people). MS was diagnosed based on the criteria of International Diabetes Fed- eration (IDF) (2005). Obesity and coronary heart disease (CHD) patients were diagnosed according to WHO cri- teria. Patients were administered a standard set of drug therapy for coronary artery disease: atorvastatin 10 mg per day, cardiket 20 mg 2 times a day, cardiomagnyl 75 mg 1 time per day. Previous antihypertensive therapy was replaced with ramipril at a dose of 5 to 10 mg/day (range Ramah, Vorvah, Pharma Hmbhiko) with dose titration in the first month of admission, depending on the initial level of blood pressure and the cardiovascular system (CVS), then after blood pressure reduction to the benchmark (139/89 mmHg) was dose ramipril 5 mg daily. Previous hypoglycemic therapy in patients with type replaced by metformin at a dose of 1000 mg per day (Glyukofazh XR, Nikomed). To reduce possible dyspeptic symptoms to a minimum, the first week, patients received 500 mg Glyu- kofazh XR per day during meals. Patients without diabetes to MS to get started metformin (Glyukofazh) at the same dose addition. With all of the patients were also discussed and corrected daily dietary issues and feasible exercise, individualized for each patient. Six-month use of a combination of metformin with ramipril (1,000 mg and 5 mg per day) in the complex treatment of the metabolic syndrome leads to improved clinical course of CHD. Patients pre- senting significantly fewer complaints including on cardiac pain, decreased duration and frequency. Complained of intermittent pain in my heart and headaches at least half of the patients (under 10 people – 41. 6 %, 8 people – 33. 3 %), most patients with type 2 diabetes. In 7 (29 % vs. 79. 1 %) patients remained short of breath on exertion. Other complaints were absent. Attacks of angina was recorded clinically in 14 (58. 0 % vs. 75. 9 %) patients, significantly decreased their duration and frequency. Was recorded further significant positive trend and anthropometric indica- tors. Continued significant reduction in body weight (104,5 ± 18,6 to 109,62 ± 16,13 kg., P < 0. 05), waist circumfer- ence (111,37 ± 121,47 to 118, 92 ± 11,96 cm, p < 0. 05), BMI decreased (33,65 ± 4,98 vs. 35, 55 ± 5,26; p < 0. 05). Normalization of blood pressure and reduction of abdominal obesity, which can be regarded as preventing the development of type 2 diabetes and its cardiovascular complications. The combination of metformin and ramipril in the complex treatment of the metabolic syndrome is an effective and safe treatment option metabolic syndrome. MF, with current data, is an antagonist of nuclear factor kB (NFkB) – the main activator of inflammation. MF also increases insulin sensitivity in the liver and muscles, which reduces the production of glucose by the liver and in- creases the flow of glucose into muscle. It lowers blood glucose and insulin levels and eliminate the main factors of progression of coronary artery disease and disorders of carbohydrate metabolism. At the molecular mechanisms of MF primary importance given to inhibition of tissue respiration and activation of adenosine pyruvatkinazа (AMPK) – an energy sensor cells. Ramipril is an inhibitor of the enzyme the turning anhiotenzin (IAPF). IAPF traditionally con- sidered mainly as antihypertensive drugs. However, recent data suggest that ACE inhibitors may affect the vascular wall by reducing endothelial dysfunction, decreased growth and proliferation of vascular smooth muscle, blocking the adverse effects of macrophages; have antioxidant effects that inhibit platelet aggregation. In addition, ACE inhibitors can increase insulin sensitivity. Just ramipril showed these effects in numerous clinical trials, DREAM and ONTARGET. In MICRO-HOPE study demonstrated that ramipril has cardio and angioprotective effects.

metabolic syndrome, diabetes mellitus type 2, CHD, metformin, ramipril

• Кайдашев И. П. Изменение образа жизни как часть комплексной терапии при метаболическом синдроме / И. П. Кай- дашев // Международный эндокринологический журнал. – 2012. – № 2. – С. 42.
• Кайдашев И. П. NF-kB-сигнализация как основа развития системного воспаления, инсулинорезистентности, липо- токсичности, сахарного диабета 2-го типа и атеросклероза / И. П. Кайдашев // Международный эндокринологиче- ский журнал. – 2011. – № 3. – С. 35-45.
• Alberti K. G. Metabolic syndrome – a new worldwide definition A Consensus Statement from the International Diabetes Fed- eration / K. G. Alberti, P. Zimmet, J. Shaw // Diabet Med. – 2006. – Vol. 23, № 5. – P. 469-480.
• Rosenson R. S. Therapeutic approaches in the prevention of cardiovascular disease in metabolic syndrome and in patients with type 2 diabetes / R. S. Rosenson, C. A. Reasner // Curr. Opin. Cardiol. – 2004. – Vol. 19, № 5. – P. 480-487.

«Bulletin of problems biology and medicine» Issue 3 part 1 (110), 2014 year, 304-307 pages, index UDK 616-008. 9-08:615.