Effect Of Aliskerin On Glycosylated Serum Protein In Essential Hypertensive Patient

Objective: Hypertension studies shown that more than 50% hypertensive patients accompanied by insulin resistance (IR) or type 2 diabetes, essential hypertensive patients complicated with glucose metabolism disorders easily. When we choose antihypertensive drugs, we should focus on the improving glucose metabolism capability, they can prevent and treat such diseases effectively. Renin-angiotensin system (RAS) blockers is the first choice, they can improving the glucose metabolism, in addition to lower blood pressure. In some researches such as HOPE, PEACE, EURO, PA, CHARM, SOLVD-T and so on, ACEI and ARB both shown improving insulin sensitivity, insulin resistance and glucose metabolism, reducing the incidence of new diabetes, comparetion with placebo. Aliskiren is a new generation of renin inhibitor, it can block the first segment of the RAS system high selectively. Now a great deal of studies have shown that Aliskiren has fewer adverse reactions, long-lasting performance in antihypotensive effect, the treatment compliance was relatively good. Aliskiren, ACEI and ARB all belong to the RAS blockers, in view of ACEI, ARB buth can improve glucose metabolism, so we look forward Aliskiren may also improve insulin resistance and glucose metabolism. In this study, by comparing Aliskiren's with ramipril's impact on antihypotensive, insulin sensitivity, insulin resistance, fasting insulin levels (FINS) and glycosylated serum protein (GSP) in essential hypertensive patients, this study explored Aliskiren's effect on antihypertensive and glucose metabolism.Methods: We chose mild-moderate essential hypertension patients in the Second Hospital of Hebei Medical University cardiovascular medicine outpatient from October 2007 to November 2008. The patients must meet all the inclusion criteria and no exclusion criteria, then they were randomized to aliskiren 75, 150, 300mg or Ramipril 5mg once daily for 8 weeks. recording these age, height, weight, body mass index (BMI), waist circumference (WC), hipcircumference (HC), waist-hip ratio(WHR), glycosylated hemoglobin (HBALC), oral glucose tolerance test line (OGTT2h) before double -blind period, Before and after treatment they were measured sitting blood pressure for three times, and were collected cubital vein blood samples, detecting fasting blood glucose (FBG), fasting insulin (INS), glycosylated serum protein (GSP), total cholesterol (TC), low density lipoprotein (LDL) were detected before and after the treatment.then calculated Insulin resistance index (IR = FINS*FPG /22.5), insulinsensitivity index (ISI=Ln (1/FIN*FBG)). Statistical Analysis: All data analysis applicates SPSS13.0 statistical software, data denotation use mean± standard deviation. The non-normal distribution of data use ln converted,then to the analysis (such as serum insulin). The normal distribution of data, comparison inside group uses paired ttest, comparison between groups uses analysis of variance (ANOVA) and analysis of covariance, p<0.05 is deemed to have significant statistical difference.Results: There were 78 patients who completed the trial. they were randomly divided into four treatment groups, taking Aliskiren 300mg group: 20 cases, Aliskiren 150mg group: 20 cases, Aliskiren 75mg group: 18 cases, Ramipril 5mg group: 20 cases respectively. There was no significant difference among the four groups of age, height, weight, WC, HC, FBG, blood lipids, OGTT2h (P>0.05).1 Before and after the treatment, the msSBP of four groups (according to the above sequence) were separately 146.82±10.46mmHg vs 130.90±8.37mmHg; 146.17±9.29 mmHg vs 133.18±10.13mmHg; 143.18±9.31mmHg vs 135.80±10.16mmHg; 145.58±5.46mmHg vs 134.24±8.46 mmHg. Before and after treatment, the msDBP of four groups (according to the above sequence) separately were 98.52±5.62mmHg vs 83.75±6.86mmHg; 99.68±5.03mmHg vs 88.91±4.25mmHg; 98.43±4.61mmHg vs 92.65±4.63mmHg; 98.98±4.99 mmHg vs 88.23±4.66mmHg. Before double-blind treatment, the msSBP and msDBP of four groups were no statistically significant differences (P>0.05), comparison among the four groups; After treatment, the msSBP and msDBP of four groups were marked declined, comparison within each group, that were statistically significant differences (P<0.05); The three groups of Aliskiren were further compared with the control group Ramipril 5mg separately, which shows that the msDBP of Aliskiren 300mg was lower than that of Ramipril 5mg (P<0.05); The msDBP of Aliskiren 75mg was higher than that of Ramipril 5mg (P<0.05); There was no significantly difference between Aliskiren 150mg and Ramipril 5mg (P>0.05). The msSBP also showed the same trend as msDBP, but the difference failed to achieve statistically significant.2 Before and after the treatment, comparison within each group, the FBG FINS ISI IR of Aliskiren 300 mg group and Ramipril 5mg group comparison within each group, that was statistically significant differences (P<0.05), Aliskiren 150 mg group and 75 mg group both can improving FINS, ISI, IR, but that were no statistically significant differences (P>0.05); that Intergroup comparison FINS, ISI, IR of the four groups that were no significant difference before and after treatment (P>0.05). Before and after treatment, the FBG of the four groups comparison within each group and comparison among groups all were no statistically differences (P>0.05). Before and after the treatment, the GSP of the four groups (according to the above sequence) separately were 254.76±13.27 umol/L vs 250.59±9.82umol/L(P>0.05); 251.87±17.26umol/L vs 248.82±13.42umol/L (P>0.05); 251.38±17.84umol/L vs 249.25±14.85umol/L(P>0.05); 252.91±11.58umol/L vs 249.58± 9.57umol/L(P<0.05). Before and after treatment, comparison GSP within each group, that were no statistical significant difference in Aliskiren300 mg, 150mg, 75mg and Ramipril 5mg groups(P>0.05), but they all can improving GSP lightly, Before and after treatment, comparation among the four groups were no statistically significant differences(P>0.05). Using analysis of covariance in Aliskiren 300 mg and Ramipril 5mg group respectily, the margin of FINS, ISI, IR of each group before and after the treathment, there were statistically significant differences(P<0.05), after deducting the initial FINS, ISI, IR factors.Conclusion: 1 In the antihypertensive efficacy, Aliskiren has a clear antihypotensive effect and dose-dependent manner, the antihypertensive effect of Aliskiren 150mg and Ramipril 5mg was Similar.2 On improving of glucose metabolism, Aliskiren 300mg and Ramipril 5mg both can improve ISI, IR, and reduce the level of FINS significantly,but has no significant effect on glycosylated serum protein.