The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study.
The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study.
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DOI：
10.1007/s00125-008-1239-x
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发表时间：
2009-03
期刊：
影响因子：
8.2
通讯作者：
Krakoff, J.
中科院分区：
文献类型：
--
作者：
Koska, J.;Ortega, E.;Bunt, J. C.;Gasser, A.;Impson, J.;Hanson, R. L.;Forbes, J.;de Courten, B.;Krakoff, J.
关键词：
低度炎症可能导致肥胖相关的胰岛素抵抗，并与2型糖尿病的风险增加有关。目前的研究评估了水杨酸盐（一种传统的抗炎药物）治疗是否会改善肥胖非糖尿病患者的胰岛素作用。该研究是一项随机、双盲、安慰剂对照、平行试验，在NIDKK （Phoenix， AZ， USA）住院临床研究单位进行。参与者为54名成年人（18 - 45岁），BMI≥30 kg/m2。干预是水杨酸盐（3g /天，n=28）或相同的安慰剂（n=26），持续7天。通过只给研究者一个对应于一瓶安慰剂或水杨酸盐的数字，按性别顺序随机分组，从而隐瞒了分配。主要结果是胰岛素作用的变化，通过血糖-高胰岛素钳夹（胰岛素输注率40 mU m−2 min−1）和75 g OGTT的葡萄糖耐量来评估葡萄糖处置率（Rd）。47名参与者完成了这项研究，其中40人进行了分析（水杨酸盐22例，安慰剂18例）。水杨酸盐治疗导致OGTT期间空腹血糖浓度（平均[SD]； 4.83 [0.28] vs 5.11 [0.33] mmol/l, p=0.001）和葡萄糖AUC降低（p=0.01）， Rd升高（20 [8]vs 18 [6] μmol [kg估计代谢体大小]−1 min−1，p=0.002），而安慰剂组这些变量无显著变化（p>均为0.3）。在钳夹期间测量的胰岛素浓度（701 [285]vs 535 [201] pmol/l, p<0.0001）正常化后，水杨酸盐对Rd的影响消失（p=0.9）。研究期间未观察到水杨酸盐的副作用。水杨酸盐的降血糖潜力似乎是由于对胰岛素浓度的影响，而不是改善胰岛素的作用。基于水杨酸的化合物可能对治疗和预防2型糖尿病有用。
Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI≥30 kg/m2. The intervention was salsalate (3 g/day, n=28) or identical placebo (n=26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal (Rd) by euglycaemic–hyperinsulinaemic clamp (insulin infusion rate 40 mU m−2 min−1) and glucose tolerance by 75 g OGTT. The study was completed by 47 participants, of which 40 were analysed (salsalate n=22, placebo n=18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p=0.001) and glucose AUC during the OGTT (p=0.01), and in increased Rd (20 [8] vs 18 [6] μmol [kg estimated metabolic body size]−1 min−1, p=0.002), while there was no significant change in these variables with placebo (p>0.3 for all). The effect of salsalate on Rd disappeared (p=0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p<0.0001) measured during the clamp. No side effects of salsalate were observed during the study. The glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes.
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