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Pharmacodynamic Effects of Low‐Dose Pioglitazone in Patients with the Metabolic Syndrome without Diabetes Mellitus
Author(s) -
Vu Anh,
Kosmiski Lisa A.,
Beitelshees Amber L.,
Prigeon Ronald,
Sidhom Maha S.,
Bredbeck Brooke,
Predhomme Julie,
Deininger Kimberly M.,
Aquilante Christina L.
Publication year - 2016
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1713
Subject(s) - pioglitazone , adiponectin , medicine , metabolic syndrome , placebo , diabetes mellitus , endocrinology , insulin resistance , insulin , pharmacodynamics , gastroenterology , type 2 diabetes , pharmacokinetics , pathology , alternative medicine
Study Objective To determine the effects of low‐dose pioglitazone on plasma adipocyte‐derived cytokines, high‐sensitivity C‐reactive protein (hs‐CRP), and components of the metabolic syndrome in adults with the metabolic syndrome without diabetes mellitus. Design Prospective, randomized, double‐blind, placebo‐controlled study. Setting University of Colorado Clinical and Translational Research Center. Patients Thirty‐two men and women, aged 30–60 years, without diabetes who had a clinical diagnosis of the metabolic syndrome, as defined by the American Heart Association/National Heart, Lung, and Blood Institute criteria. Intervention Patients were randomly assigned to receive oral pioglitazone 7.5 mg daily or matching placebo for 8 weeks. Measurements and Main Results The primary end point was the change in plasma high‐molecular‐weight (HMW) adiponectin level from baseline to week 8. Other end points were changes in plasma total adiponectin, omentin, and hs‐CRP levels, and changes in components of the metabolic syndrome (e.g., insulin sensitivity) from baseline to week 8. Pioglitazone was associated with a significant increase in plasma HMW adiponectin from baseline to week 8 compared with placebo (+47% vs −10%, p<0.001). Insulin sensitivity increased significantly from baseline to week 8 in the pioglitazone group (+88%, p=0.02) but not in the placebo group (+15%, p=0.14). Change in HMW adiponectin was significantly correlated with the change in insulin sensitivity in the pioglitazone group ( r = 0.784, p=0.003). No significant differences in mean percentage changes in plasma total adiponectin, omentin, and hs‐CRP levels were observed between the pioglitazone and placebo groups. Likewise, changes in body weight, insulin sensitivity, glucose, lipids, and blood pressure did not differ significantly between the groups. Conclusion Low‐dose pioglitazone favorably modulates plasma HMW adiponectin, which was associated with an improvement in insulin sensitivity, in patients with the metabolic syndrome without diabetes.