Salsalate improves glycemia and inflammatory parameters in obese young adults

Abstract

Objective: 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.

Research design and methods: In a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo.

Results: 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).

Conclusions: 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.

Figure 1

Changes in glycemia, insulin, and C-peptide. A: Fasting glucose, AUC after an OGTT, and glycated albumin were reduced in salsalate-treated subjects compared with the placebo group. B: The salsalate-treated group (left panel) showed improvements in glycemia after an OGTT compared with the placebo group (right panel). Mean and SEM data are shown before and 30, 60, 90, and 120 min after 75 g oral glucose. ○, baseline data. C and D: Data for insulin (C) and C-peptide (D) are shown before and 30, 60, 90, and 120 min after a 75-g oral glucose load for both the salsalate-treated (left panels) and placebo (right panels) groups. AUC, area under the curve.

Figure 2

Changes in inflammatory markers and mediators. A: Adiponectin increased significantly in the salsalate-treated group compared with the placebo group. B: CRP and FFA were lower after salsalate (upper panel) but unchanged after placebo (lower panel) by within-group analysis (*P < 0.05). , baseline; ■, after therapy.