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Harvard Medical School, Boston, MA 02115 1Joslin Diabetes Center, Boston, MA 02215
2Children's Hospital Boston, Boston, MA 02115
allison.goldfine@joslin.harvard.edu
ABSTRACT
Objective: Sedentary lifestyle and 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 mellitus.
Research Design and Methods: In a double-masked placebo controlled trial, we evaluated 20 obese non-diabetic adults at baseline and after one-month of salsalate or placebo.
Results: Compared to placebo, salsalate reduced fasting glucose 13% (p<0.002), glycemic response following an oral glucose challenge 20% (p<0.004), and glycated albumin 17% (p<0.0003). While insulin levels were unchanged, fasting and OGTT C-peptide levels decreased in the salsalate treated subjects compared to placebo (p<0.03), consistent with improved insulin sensitivity and a known effect of salicylates to inhibit insulin clearance. Adiponectin increased 57% following salsalate compared with placebo (p<0.003). Additionally, within the group of salsalate treated subjects, circulating levels of CRP were reduced by 34% (p<0.05).
Conclusions: In this proof-of-principle study, salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight persons. These data support the hypothesis that subacute-chronic inflammation contributes to the pathogenesis of obesity related dysglycemia, and targeting inflammation may provide a therapeutic route for diabetes prevention. |
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