Salsalate and glycemia in obese young adults

Nutrition Research Newsletter, March, 2008

Obesity, occurring at epidemic rates worldwide, is a major risk factor for diabetes and cardiovascular disease. There is an urgent need for effective interventions to prevent diabetes in obese population. The importance of lifestyle modification in obesity and diabetes is well recognized. However, disappointing long-term results of these treatments have led to increased interest in pharmaceutical intervention. Obesity and high-fat western diets activate inflammatory processes, which promote development of insulin resistance. Thus, targeting the inflammatory pathway may be a novel pharmacologic intervention for diabetes prevention and treatment.

Salicylates are among the most commonly used nonsteroidal anti-inflammatory drugs. High doses of the salicylate aspirin improve fasting and postprandial hyperglycemia in patients with diabetes. As a nonacetylated salicylate, salsalate is an inhibitor of NF-B but has a lower bleeding risk than aspirin.

Investigators performed a study to assess metabolic changes with administration of salicylates to obese individuals without diabetes. It was hypothesized that salicylates administered for 1 month would improve glycemia in obese young adults. Subjects were <30 years and obese, with BMI e" 30. Participants were instructed to consume a high-carbohydrate diet (250 g/day to 300 g/day) and abstain from strenuous exercise for 3 days before evaluations and not to alter dietary or exercise habits during the study. Blood pressure as measured twice. Fasting lipids and cytokines were measured, and oral glucose tolerance tests (OGTTs) were performed with glucose, insulin, and C-peptide levels measured before and 30, 60, 90, and 120 minutes after a 75-gram glucose load. All subjects were non diabetic. Insulin resistance was determined. Subjects were randomly assigned to receive salsalate, 4.0 g/d divided in tow doses, or identical placebo for 4 weeks.

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 study demonstrates that salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight persons.

A. Fleischman, S. Shoelson, R. Bernier, et al. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care; 31:289-294 (February, 2008). [Correspondence: Allison B. Goldfine, MD, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: Allison.goldfine@joslin.harvard.edu.]