OR31-2 Effects of Colchicine on Insulin Resistance, Pancreatic Beta-Cell Function, and Aspects of the Metabolic Syndrome (MetS) in Adults with Obesity, MetS, and Inflammation: A Pilot Randomized Controlled Trial

Introduction: Low-grade chronic inflammation, due in part to activation of the NLRP3 inflammasome, increases with increasing adiposity and plays a significant role in the development of type 2 diabetes and cardiovascular disease. However, to date, the efficacy of anti-inflammatory medications to improve aspects of the metabolic syndrome (MetS) is not well established. As colchicine has been shown to prevent assembly of the NLRP3 inflammasome and ameliorate other inflammatory conditions, we aimed to evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in adults with obesity and MetS. Materials and Methods: We conducted a randomized, double-blind, placebo-controlled pilot trial in which 40 non-diabetic adults with obesity, MetS, and elevated high-sensitivity C-reactive protein (hsCRP≥ 2.0 mg/L) were randomized to colchicine 0.6 mg or placebo twice daily for three months. Fasting labs, insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT), and body composition by DXA were performed at baseline and 3-month follow up. The primary outcome was change in FSIVGTT insulin sensitivity (SI) as measured by Bergman’s minimal model. Secondary outcomes included changes in other metabolic parameters and inflammatory markers. ANCOVA was used to examine differences between treatment arms, with age, sex, baseline body fat%, and Δbody fat% as covariates. Data were analyzed according to intention-to-treat and reported as mean±SD. Results: Colchicine significantly reduced inflammatory indices, including hsCRP (-2.8±2.9 vs. 0.4±2.8 mg/L, p=.002), ESR (-5.5±6.4 vs. 0.6±6.3 mm/hr, p=.007), white blood cell count (-1.09±1.23 vs. 0.29±1.16 K/µL, p=.002), and absolute neutrophil count (-1.06±1.05 vs. 0.12±0.93 K/µL, p