Abstract 13824: Salsalate Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome

Abstract

Background: Insulin resistance accelerates systemic inflammation and vascular dysfunction. Salsalate suppresses inflammation and may improve insulin sensitivity and insulin-mediated, endothelium-dependent vasodilation. Hypothesis: We hypothesized that salsalate treatment would improve insulin-stimulated forearm blood flow (FBF) in volunteers with metabolic syndrome compared to placebo. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00760019) evaluating 4-weeks of salsalate 1.5 grams TID on insulin-stimulated FBF during an insulin clamp in patients with and without metabolic syndrome. Results: Nineteen patients received salsalate (13 metabolic syndrome and 6 healthy controls). Patients with metabolic syndrome were older (36.3 vs 57.1 years old, p=0.002) with higher BMIs (33.9 vs 25.5 kg/m 2 , p=0.001) and higher insulin levels (10.8 vs 4.3 μU/mL, p=0.01). Those with metabolic syndrome had impaired insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR, 2.66 vs 0.87, p=0.005) and Matsuda Index (MI, 5.81 vs 3.32, p=0.001). After salsalate treatment, insulin sensitivity was unchanged (Panel A & B) and there was no significant reduction in insulin levels (Panel C) or inflammation by C-reactive protein (Panel D). Insulin stimulation increased FBF in patients treated with placebo (p=0.012) and salsalate (p=0.003), but salsalate blunted the FBF response in those with metabolic syndrome (p=0.022, Panel E). In multivariable linear regression, metabolic syndrome, HOMA IR, and MI associated with insulin-stimulated FBF independent of salsalate treatment. Conclusion: Salsalate improved neither insulin sensitivity nor systemic inflammation, and it blunted insulin-stimulated vasodilation in patients with metabolic syndrome. Salsalate does not modulate systemic inflammation and worsens arteriolar endothelial dysfunction in patients with metabolic syndrome.