血管紧张素受体阻滞剂/利尿剂联合治疗可改善肥胖高血压患者的胰岛素反应。
Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives.
机构信息
Diabetes and Cardiovascular Center, University of Missouri School of Medicine, and VA Medical Center, Columbia, Missouri 65212, USA.
出版信息
J Hypertens. 2010 Aug;28(8):1761-9. doi: 10.1097/HJH.0b013e32833af380.
BACKGROUND
Thiazide diuretics can impair glucose metabolism and increase new-onset diabetes. Adding an angiotensin receptor blocker to diuretics may protect against these metabolic effects; however, the mechanism of this protection is unclear.
METHOD
To explore potential mechanisms, a 16-week multicenter trial was conducted to ascertain the relative glucose metabolism effects of combined hydrochlorothiazide and angiotensin receptor blocker (valsartan) therapy compared with hydrochlorothiazide and calcium channel blocker (amlodipine) treatment in 412 centrally obese hypertensive individuals (BMI = 35 +/- 7 kg/m, seated BP = 159 +/- 8/94 +/- 8 mmHg, and mean age 56 years). Individuals were randomized to valsartan/hydrochlorothiazide, with force-titration to 320/25 mg or hydrochlorothiazide, with titration to hydrochlorothiazide 25 mg and amlodipine 10 mg, respectively. Changes from baseline to week 16 in fasting and 2-h postprandial glucose and insulin levels after an oral glucose load were measured.
RESULTS
At week 16, clinic blood pressure reductions were similar (P > 0.05) in both groups. Fasting and 2-h glucose levels increased (P < 0.05) with the amlodipine combination but not with the valsartan combination. In concert with these glucose responses, postprandial insulin increases from baseline were substantially greater with valsartan than with amlodipine plus hydrochlorothiazide group (P = 0.001). The glucose responses were inversely related to insulin responses at the study conclusion.
CONCLUSION
The novel observation of this investigation was that the combination of valsartan and hydrochlorothiazide was associated with greater glucose-stimulated insulin secretory and lesser glycemic excursion responses than the amlodipine combination group. Thus, this data suggests that adding an angiotensin receptor blocker attenuates the negative effects of thiazides on pancreatic beta-cell glucose-induced insulin secretion.
背景
噻嗪类利尿剂可损害葡萄糖代谢，增加新发糖尿病。在利尿剂的基础上加用血管紧张素受体阻滞剂（ARB）可能有助于预防这些代谢作用，但具体的保护机制尚不清楚。
方法
为了探讨潜在的机制，进行了一项为期 16 周的多中心试验，比较了联合应用氢氯噻嗪和血管紧张素受体阻滞剂（缬沙坦）与氢氯噻嗪和钙通道阻滞剂（氨氯地平）治疗对中心性肥胖高血压患者（BMI = 35 ± 7 kg/m，坐位血压 = 159 ± 8/94 ± 8 mmHg，平均年龄 56 岁）相对葡萄糖代谢的影响。将患者随机分为缬沙坦/氢氯噻嗪组，剂量滴定至 320/25 mg；或氢氯噻嗪组，剂量滴定至氢氯噻嗪 25 mg 和氨氯地平 10 mg。测量口服葡萄糖负荷后空腹和餐后 2 小时血糖及胰岛素水平的变化。
结果
第 16 周时，两组的诊室血压降低幅度相似（P > 0.05）。与氨氯地平联合治疗组相比，氢氯噻嗪联合治疗组的空腹血糖和餐后 2 小时血糖水平升高（P < 0.05）。与这些血糖反应一致，缬沙坦组的餐后胰岛素反应较氨氯地平/氢氯噻嗪组显著增加（P = 0.001）。研究结束时，葡萄糖反应与胰岛素反应呈负相关。
结论
本研究的新发现是，与氨氯地平联合治疗组相比，缬沙坦与氢氯噻嗪联合治疗组的葡萄糖刺激胰岛素分泌反应更大，血糖波动更小。因此，该研究结果提示，加用 ARB 可减弱噻嗪类药物对胰岛β细胞葡萄糖诱导的胰岛素分泌的不良影响。
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