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Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults

¹ Harvard Medical School, Boston, Massachusetts
² Joslin Diabetes Center, Boston, Massachusetts
³ Children's Hospital Boston, Boston, Massachusetts

Address correspondence and reprint requests to Allison B. Goldfine, MD, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: allison.goldfine{at}joslin.harvard.edu

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.

Abbreviations: ALT, alanine aminotransferase • AST, aspartate aminotransferase • CRP, C-reactive protein • FFA, free fatty acid • HOMA-IR, homeostasis model assessment of insulin resistance • HOMA-IR_C-peptide, homeostasis model assessment of insulin resistance calculated using C-peptide • IKKβ, IB kinase complex β • NF-B, nuclear factor-B • OGTT, oral glucose tolerance test

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