title: Insulin sensitizing and anti-inflammatory effects of thiazolidinediones are heightened in obese patients.
abstract: OBJECTIVE
  The American Diabetes Association has called for further research on how patients' demographics should determine drug choices for individuals with type 2 diabetes mellitus (T2DM). Here, using in-depth physiology studies, we investigate whether obese patients with T2DM are likely to benefit from thiazolidinediones, medications with a known adverse effect of weight gain.
  
  
  METHODS
  Eleven obese and 7 nonobese individuals with T2DM participated in this randomized, placebo-controlled, double-blind, crossover study. Each subject underwent a pair of "stepped" pancreatic clamp studies with subcutaneous adipose tissue biopsies after 21 days of pioglitazone (45 mg) or placebo.
  
  
  RESULTS
  Obese subjects demonstrated significant decreases in insulin resistance and many adipose inflammatory parameters with pioglitazone relative to placebo. Specifically, significant improvements in glucose infusion rates, suppression of hepatic glucose production, and whole fat expression of certain inflammatory markers (IL-6, IL-1B, and inducible nitric oxide synthase) were observed in the obese subjects but not in the nonobese subjects. Additionally, adipose tissue from the obese subjects demonstrated reduced infiltration of macrophages, dendritic cells, and neutrophils as well as increased expression of factors associated with fat "browning" (peroxisome proliferator-activated receptor gamma coactivator-1α and uncoupling protein-1).
  
  
  CONCLUSIONS
  These findings support the efficacy of pioglitazone to improve insulin resistance and reduce adipose tissue inflammation in obese patients with T2DM.
authors.affiliation: From the *Division of Endocrinology, Department of Medicine, and †Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Yonah B
authors.initials: YB
authors.lastname: Esterson
authors.forename: Kehao
authors.initials: K
authors.lastname: Zhang
authors.forename: Sudha
authors.initials: S
authors.lastname: Koppaka
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kehlenbrink
authors.forename: Preeti
authors.initials: P
authors.lastname: Kishore
authors.forename: Pooja
authors.initials: P
authors.lastname: Raghavan
authors.forename: Sylvan Roger
authors.initials: SR
authors.lastname: Maginley
authors.forename: Michelle
authors.initials: M
authors.lastname: Carey
authors.forename: Meredith
authors.initials: M
authors.lastname: Hawkins
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000188:drug therapy; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D045162:Thiazolidinediones; D000077205:Pioglitazone