Diabetes Center, Department of Internal Medicine, Vrije University Medical Center, Amsterdam, the Netherlands.
Diabetes Care. 2011 Apr;34(4):845-51. doi: 10.2337/dc10-2224. Epub 2011 Feb 17.
Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes.
In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex.
Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P < 0.001). BMI remained unchanged in both treatment groups (P = 0.89).
Twenty-six weeks of valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes.
最近，那格列奈和缬沙坦在糖耐量受损结局研究试验中表明，用血管紧张素受体阻断剂（ARB）缬沙坦治疗 5 年可使葡萄糖代谢受损（IGM）患者 2 型糖尿病的发病率相对降低 14%。我们研究了 ARB 缬沙坦在预防 2 型糖尿病发病中的这些预防作用是否归因于β细胞功能和/或胰岛素敏感性的改善。
在这项随机对照、双盲、双中心研究中，在空腹血糖受损和/或糖耐量受损的患者中，使用联合高胰岛素-正常血糖和高血糖钳夹试验，并随后进行精氨酸刺激和 2 小时 75g 口服葡萄糖耐量试验（OGTT），评估 26 周缬沙坦（每天 320mg；n=40）或安慰剂（n=39）对β细胞功能和胰岛素敏感性的影响。采用协方差分析（ANCOVA）分析治疗效果，调整中心、糖代谢状态和性别。
与安慰剂相比，缬沙坦增加了第一相（P=0.028）和第二相（P=0.002）葡萄糖刺激的胰岛素分泌，而两组间增强的精氨酸刺激的胰岛素分泌无差异（P=0.25）。此外，缬沙坦增加了 OGTT 衍生的胰岛素原指数（代表口服葡萄糖负荷后的第一相胰岛素分泌；P=0.027）。与安慰剂相比，钳夹试验中胰岛素敏感性显著增加（P=0.049）。与安慰剂相比，缬沙坦治疗可显著降低收缩压和舒张压（P<0.001）。两组的 BMI 均无变化（P=0.89）。
26 周缬沙坦治疗可增加血压正常的 IGM 患者的葡萄糖刺激胰岛素释放和胰岛素敏感性。这些发现可能部分解释了缬沙坦在降低 2 型糖尿病发病率方面的有益作用。
