Fleischman Amy, Shoelson Steven E, Bernier Raquel, Goldfine Allison B
Harvard Medical School, Boston, Massachusetts, USA.
Diabetes Care. 2008 Feb;31(2):289-94. doi: 10.2337/dc07-1338. Epub 2007 Oct 24.
Sedentary lifestyle and a western diet promote subacute-chronic inflammation, obesity, and subsequently dysglycemia. The aim of the current study was to evaluate the efficacy of the anti-inflammatory drug salsalate to improve glycemia by reducing systemic inflammation in obese adults at risk for the development of type 2 diabetes.
In a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo.
Compared with placebo, salsalate reduced fasting glucose 13% (P < 0.002), glycemic response after an oral glucose challenge 20% (P < 0.004), and glycated albumin 17% (P < 0.0003). Although insulin levels were unchanged, fasting and oral glucose tolerance test C-peptide levels decreased in the salsalate-treated subjects compared with placebo (P < 0.03), consistent with improved insulin sensitivity and a known effect of salicylates to inhibit insulin clearance. Adiponectin increased 57% after salsalate compared with placebo (P < 0.003). Additionally, within the group of salsalate-treated subjects, circulating levels of C-reactive protein were reduced by 34% (P < 0.05).
This proof-of-principle study demonstrates that salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight individuals. These data support the hypothesis that subacute-chronic inflammation contributes to the pathogenesis of obesity-related dysglycemia and that targeting inflammation may provide a therapeutic route for diabetes prevention.
久坐不动的生活方式和西方饮食会引发亚急性-慢性炎症、肥胖,进而导致血糖异常。本研究旨在评估抗炎药物双水杨酯通过减轻有2型糖尿病发病风险的肥胖成年人的全身炎症来改善血糖的疗效。
在一项双盲、安慰剂对照试验中,我们对20名肥胖非糖尿病成年人在基线时以及服用双水杨酯或安慰剂1个月后进行了评估。
与安慰剂相比,双水杨酯使空腹血糖降低了13%(P<0.002),口服葡萄糖耐量试验后的血糖反应降低了20%(P<0.004),糖化白蛋白降低了17%(P<0.0003)。虽然胰岛素水平未发生变化,但与安慰剂相比,接受双水杨酯治疗的受试者空腹及口服葡萄糖耐量试验的C肽水平降低(P<0.03),这与胰岛素敏感性提高以及水杨酸盐抑制胰岛素清除的已知作用一致。与安慰剂相比,服用双水杨酯后脂联素增加了57%(P<0.003)。此外,在接受双水杨酯治疗的受试者组中,循环中的C反应蛋白水平降低了34%(P<0.05)。
这项原理验证研究表明,双水杨酯可降低血糖,并可能改善超重个体的炎症性心血管风险指标。这些数据支持以下假设:亚急性-慢性炎症促成了肥胖相关血糖异常的发病机制,针对炎症可能为糖尿病预防提供一条治疗途径。