Objective: omega-3 Polyunsaturated a-linolenic acid (ALA) supplementation has not been studied in the setting of adiponectin levels and insulin sensitivity (IS) improvements in patients with type 2 diabetes mellitus (T2DM) by hyperinsulinemic-euglycemic clamp (HEC). The aim of this study was to examine the influence of w-3 ALA on IS and adiponectin. Methods: We conducted a randomized study in patients with T2DM and assessed IS using HEC. Twenty patients with T2DM were included and randomly assigned to receive 3 g/d of ALA or placebo for 60 d, in a double-blind design. The assessment of IS by HEC was performed at baseline and after 60 d in all patients; blood samples were taken for the measurement of serum lipids, glucose, insulin, adiponectin, and cytokines. The primary outcome variables were an increase of both glucose infusion rate (GIR) in steady state and glucose metabolization (M) by HEC. The secondary outcomes were an increase in adiponectin levels and a decrease in fasting plasma glucose, glycated hemoglobin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, lipids and cytokines. The study was conducted at an academic medical center. Results: The ALA group improved IS corrected for fat-free mass (M/FFM; P = 0.04). Both groups showed increased adiponectin after 60 d (P = 0.01), however, the increase for the ALA group was greater (P = 0.04). In the ALA group, adiponectin was positively correlated with GIR (r = 0.76; P= 0.01) and M/FFM (r = 0.62; P = 0.06), and negatively correlated with HOMA-IR (r = 0.61; P = 0.03). Conclusion: omega-3 ALA supplementation improved glucose homeostasis and was associated with an increase in adiponectin. Improvement in the overall metabolic profile with omega-3 ALA suggests a potential clinical utility for this agent and requires further investigation. (C) 2015 Elsevier Inc. All rights reserved.316 853857Conselho Nacional de Desenvolvimento Cinetifico e Tecnologico [14/2012]