PMID- 24705615 OWN - NLM STAT- MEDLINE DCOM- 20141216 LR - 20211021 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 37 IP - 6 DP - 2014 Jun TI - Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW. PG - 1706-11 LID - 10.2337/dc13-1745 [doi] AB - OBJECTIVE: Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. RESEARCH DESIGN AND METHODS: A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. RESULTS: Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved beta-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 +/- 0.5 to 38 +/- 2.5 mug/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. CONCLUSIONS: Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. CI - (c) 2014 by the American Diabetes Association. FAU - Tripathy, Devjit AU - Tripathy D AD - Texas Diabetes Institute and University of Texas Health Science Center and Audie L. Murphy Hospital, South Texas VA Health Care System, San Antonio, TX. FAU - Clement, Stephen C AU - Clement SC AD - Division of Endocrinology and Metabolism, Georgetown University, Washington, DC. FAU - Schwenke, Dawn C AU - Schwenke DC AD - Phoenix VA Health Care System, Phoenix, AZCollege of Nursing and Health Innovation, Arizona State University, Phoenix, AZ. FAU - Banerji, MaryAnn AU - Banerji M AD - State University of New York Health Science Center at Brooklyn, Brooklyn, NY. FAU - Bray, George A AU - Bray GA AD - Pennington Biomedical Research Center/Louisiana State University, Baton Rouge, LA. FAU - Buchanan, Thomas A AU - Buchanan TA AD - University of Southern California Keck School of Medicine, Los Angeles, CA. FAU - Gastaldelli, Amalia AU - Gastaldelli A AD - University of Texas Health Science Center, San Antonio, TX, and Cardiometabolic Risk Unit, Institute of Clinical Physiology, Pisa, Italy. FAU - Henry, Robert R AU - Henry RR AD - VA San Diego Healthcare System and University of California, San Diego, San Diego, CA. FAU - Kitabchi, Abbas E AU - Kitabchi AE AD - Division of Endocrinology, Diabetes and Metabolism, University of Tennessee, Memphis, TN. FAU - Mudaliar, Sunder AU - Mudaliar S AD - VA San Diego Healthcare System and University of California, San Diego, San Diego, CA. FAU - Ratner, Robert E AU - Ratner RE AD - Medstar Research Institute, Hyattsville, MD. FAU - Stentz, Frankie B AU - Stentz FB AD - Division of Endocrinology, Diabetes and Metabolism, University of Tennessee, Memphis, TN. FAU - Musi, Nicolas AU - Musi N AD - Texas Diabetes Institute and University of Texas Health Science Center and Audie L. Murphy Hospital, South Texas VA Health Care System, San Antonio, TX. FAU - Reaven, Peter D AU - Reaven PD AD - Phoenix VA Health Care System, Phoenix, AZ. FAU - DeFronzo, Ralph A AU - DeFronzo RA AD - Texas Diabetes Institute and University of Texas Health Science Center and Audie L. Murphy Hospital, South Texas VA Health Care System, San Antonio, TX albarado@uthscsa.edu. LA - eng SI - ClinicalTrials.gov/NCT00220961 GR - KL2 TR001118/TR/NCATS NIH HHS/United States GR - UL1 TR000130/TR/NCATS NIH HHS/United States GR - UL1 TR001120/TR/NCATS NIH HHS/United States GR - UL1-TR-000130/TR/NCATS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140404 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Adiponectin) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Thiazolidinediones) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Adiponectin/*blood MH - Blood Glucose/analysis MH - Cohort Studies MH - Diabetes Mellitus, Type 2/*blood/*drug therapy MH - Disease Progression MH - Female MH - Follow-Up Studies MH - Glucose Intolerance/blood/*drug therapy MH - Glucose Tolerance Test MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Insulin/therapeutic use MH - *Insulin Resistance MH - Insulin-Secreting Cells/metabolism MH - Male MH - Middle Aged MH - Pioglitazone MH - Thiazolidinediones/*therapeutic use PMC - PMC4179517 EDAT- 2014/04/08 06:00 MHDA- 2014/12/17 06:00 PMCR- 2015/06/01 CRDT- 2014/04/08 06:00 PHST- 2014/04/08 06:00 [entrez] PHST- 2014/04/08 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] PHST- 2015/06/01 00:00 [pmc-release] AID - dc13-1745 [pii] AID - 1745 [pii] AID - 10.2337/dc13-1745 [doi] PST - ppublish SO - Diabetes Care. 2014 Jun;37(6):1706-11. doi: 10.2337/dc13-1745. Epub 2014 Apr 4.