Influence of different classes of antihypertensive drugs on insulin resistance in patients with mild and moderate arterial hypertension
Background. The purpose was to reveal the prevalence of metabolic syndrome in patients with hypertension and methods of correction with antihypertensive therapy. Materials and methods. 223 patients with mild to moderate hypertension and metabolic syndrome (MS) were examined according to ATP III criteria, of which 105 (47.1 %) were males and 118 (52.9 %) — females. The average age of patients was 50.29 ± 0.96 years. The average duration of hypertension is 5.01 ± 0.26 years. The average body mass index (BMI) was 32.92 ± 0.38 kg/m2. 70.16 % of the patients had hereditary hypertension complications and 24.19 % — diabetes. Excessive body mass was observed in all patients, including overweight itself in 21.77 % of the subjects, degree I obesity — in 58.06 %, degree II obesity — in 12.90 %, degree III obesity — in 7.26 %. The average levels of office systolic (SBP) and diastolic blood pressure (DBP) amounted to 157.03 ± 0.79 and 92.17 ±
± 0.32 mmHg, respectively. Average heart rate — 75.02 ± 0.69 bpm. Average figures for blood pressure with daily blood pressure monitoring were: for SBP — 135.90 ± 1.13 mmHg, for DBP — 80.38 ± 0.81 mmHg. Average daily heart rate — 71.49 ± ± 0.89 bpm. The study did not include patients with type 1 and type 2 diabetes mellitus, verified symptomatic arterial hypertension, clinical signs of coronary heart disease, heart failure, level of office blood pressure ≥ 180/110 mmHg, decompensated liver disease (alanine aminotransferase, aspartete aminotransferase 3 times above norm), acute or chronic renal insufficiency (glomerular filtration rate < 60 ml/min), myocardial infarction or acute cerebrovascular accident in the past medical history, pregnancy, and lactation. The first control group consisted of 10 apparently healthy individuals. The se-cond control group included 24 patients with mild and moderate arterial hypertension without signs of a metabolic syndrome. The average age of patients was 49.88 ± 1.52 years. The ave-
rage BMI is 25.56 ± ± 0.31 kg/m2. Carbohydrate metabolism was evaluated by oral glucose tolerance test (OGTT) according to the standard method. Normal glucose tolerance (NGT) was determined with glucose level < 6.1 mmol/l and after 2 hours < 7.8 mmol/l. Impaired fasting glucose — at a level ³ 6.1 but < 7.0 mmol/L on an empty stomach, and < 7.8 mmol/l in 2 hours. Impaired glucose tolerance — at the level < 7.0 mmol/l on an empty stomach, and > 7.8 mmol/l but < 11.1 mmol/l in 2 hours. The criteria for the diagnosis of diabetes mellitus were: fasting glucose level ³ 7.0 mmol/l and/or ³ 11.1 mmol/l in 2 hours. The presence of insulin resistance was determined at HOMA level ³ 3.0 c.u. Results. The frequency of MS components detection in our study was: 3 components (arterial hypertension and waist circumference > 88 cm in women and 102 cm in men, 2 mandatory criteria and any other of the 5 criteria) — 100 %, 4 components — 61 %, 5 components — 22 % of patients. At the first stage of the study, we compared the groups of patients with hypertension and clinical manifestations of MS and with hypertension without MS. Patients with hypertension and clinical manifestations of MS were significantly more likely to have impaired fasting glucose, impaired glucose intolerance, and HOMA was also higher as compared to the group of hypertensive patients without MS. They were more likely to have normal glucose tolerance and no cases of diabetes. In patients with hypertension and MS, hyperinsulinemia was more pronounced both on an empty stomach and at all stages of OGTT. Thus, insulin levels above 11 μU/ml were detected in 35.5 % of patients with hypertension and MS and only in 12.5 % of hypertensive patients without MS (p < 0.05). Insulin resistance by the HOMA > 3 was found in 29 % of patients with mild to moderate arterial hypertension and clinical signs of metabolic syndrome without diabetes mellitus. Thus, in our study, impaired fasting glucose, impaired glucose intolerance and newly diagnosed diabetes mellitus in patients with hypertension and MS were found in 51.61 % of cases that is much more often than in patients without MS (16.66 %) (p = 0.002), which may indicate an additional risk of developing cardiovascular diseases. After 6 months, blood pressure decreased equally in all groups of patients. The study of the drugs’ effect on glucose level showed that at the background of atenolol, an increase in glucose level by 5.61 % (p < 0.001) was observed in 6 months. According to OGTT, 6 (18.7 %) cases of diabetes mellitus when receiving atenolol were detected. The area under the glucose curve increased by 9.75 % (p < 0.001). The administration of fosinopril was accompanied by the opposite dynamics: a decrease in glucose level by 1.44 % (p = 0.003), in area under the glucose curve — by 5.63 % (p < 0.001). In the fosinopril group, there were 2 patients who were diagnosed diabetes mellitus during the observation period (6.3 %). On the background of telmisartan treatment, there was the most pronounced and significant reduction in glucose level, both fasting by 2.91 % (p < 0.001), and the area under the glucose curve by 7.67 % (p < 0.001). Following carvedilol administration, fasting glucose levels did not change significantly, and during bisoprolol treatment — decreased by 9 %, from 5.5 ± 0.1 to 5.0 ± 0.1 (p < 0.001), under the influence of nebivolol — decreased by 7.4 %, from 5.4 ± 0.1 to 5.0 ± 0.1 (p < 0.001). In the carvedilol group, there were 2 patients who had diabetes mellitus during the observation period (6.3 %). In the bisoprolol group, one case of diabetes mellitus (3.2 %) was detected during the follow-up. That is, therapy with telmisartan and nebivolol had the most positive effect on the glucose level. The study of the effect of drugs on the insulin level showed that the use of atenolol contributed to a significant increase in insulin levels, especially on an empty stomach — by 65.43 % (p < 0.001), the area under the insulin curve increased by 19.53 % (p < 0.001). Administration of fosinopril was accompanied by a decrease in insulin levels by 1.44 % (p = 0.003), the area under the insulin curve — by 21.05 % (p < 0.001). On the background of telmisartan treatment, the most pronounced and reliable decrease in insulin levels was observed. Thus, fasting insulin levels decreased by 28.19 % (p < 0.001), the area under the insulin curve — by 30.09 % (p < 0.001), which was significantly more significant compared to fosinopril group
(p < 0.05). Carvedilol therapy contributed to 22.8 % (p < 0.001) decrease in fasting insulin levels; when using bisoprolol, fasting insulin decreased by 10.7 % (p < 0.001), when using nebivolol — by 16 % (p < 0.001). That is, telmisartan treatment had the most pronounced positive effect on the level of insulin. Evaluating the effect of drugs on the state of insulin resistance, it was found that atenolol, in contrast to fosinopril and telmisartan, significantly impaired IR, which was manifested in an increase in HOMA level by 78.18 %, p < 0.001. At the same time, against the background of fosinopril treatment, IR was improved — the HOMA index decreased by 12.5 % (p < 0.001). However, even more pronounced IR improvement was observed during telmisartan treatment, when HOMA level decreased by 31.64 % (p < 0.001). The difference between the telmisartan and fosinopril group is significant (p < 0.05). Therapy with carvedilol contributed to a significant HOMA decrease by 21.7 % (p < 0.001). On the background of treatment with bisoprolol, HOMA decreased by 17.4 % (p < 0.001), in nebivolol group, HOMA reduced by 23 % (p < 0.001). Thus, telmisartan and nebivolol had the highest positive effect on IR. Conclusions. The use of telmisartan and nebivolol as monotherapy can be rational in patients with mild to moderate arterial hypertension and the clinical signs of metabolic syndrome without diabetes with manifestations of insulin resistance.
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