title: Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study.
abstract: OBJECTIVE
  We have tested whether the Pro12Ala variant of the peroxisome proliferator-activated receptor (PPAR)-gamma nuclear receptor involved in thiazolidinedione (TZD) action accounted for the failure of troglitazone to increase insulin sensitivity in nondiabetic Hispanic women with previous gestational diabetes treated in the Troglitazone in Prevention of Diabetes (TRIPOD) study.
  
  
  METHODS
  Ninety-three women assigned to troglitazone had intravenous glucose tolerance tests at randomization and after 3 months of treatment with troglitazone, 400 mg/day, and were genotyped for the Pro12Ala variant of the PPAR-gamma gene. Subjects were divided into tertiles based on their change in minimal model insulin sensitivity (S(i)) during the first 3 months of troglitazone treatment.
  
  
  RESULTS
  The mean changes in S(i) in the bottom, middle, and top tertiles of S(i) response were -0.21 +/- 0.57, 0.91 +/- 0.26, and 2.58 +/- 1.32 min(-1) per microU/ml. 10(-4), respectively. Frequencies of the Ala/- genotype were 30, 22, and 26% in the same three tertiles (P = 0.77). Analysis of phenotypes by genotype revealed only small differences between the Pro/Pro and Ala/- groups, respectively, in baseline S(i) (2.76 +/- 0.19 vs. 2.33 +/- 0.33 x 10(-4) min(-1) per microU/ml; P = 0.27), the change in S(i) after 3 months of troglitazone treatment (1.19 +/- 0.17 vs. 0.93 +/- 0.30; P = 0.46), and the cumulative incidence of diabetes during a median follow-up of 30 months (13 vs. 17%; P = 0.66).
  
  
  CONCLUSIONS
  Among young Hispanic women at high risk for type 2 diabetes, the Pro12Ala variant of the PPAR-gamma receptor gene did not explain the failure of approximately 1/3 of subjects to increase their insulin sensitivity when placed on troglitazone at a dose of 400 mg/day.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland, Baltimore School of Medicine, 660 W. Redwood St., Howard Hall Rm. 598-B, Baltimore, MD 21201-1596, USA. ssnitker@medicine.umaryland.edu
authors.forename: Soren
authors.initials: S
authors.lastname: Snitker
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: Ifeanyi
authors.initials: I
authors.lastname: Ani
authors.forename: Anny H
authors.initials: AH
authors.lastname: Xiang
authors.forename: Aura
authors.initials: A
authors.lastname: Marroquin
authors.forename: Cesar
authors.initials: C
authors.lastname: Ochoa
authors.forename: Jose
authors.initials: J
authors.lastname: Goico
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
mesh_terms: D000409:Alanine; D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002839:Chromans / Q000627:therapeutic use*; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006630:Hispanic or Latino; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011392:Proline; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000077288:Troglitazone
chemical_list: D001786:Blood Glucose; D002839:Chromans; D017931:DNA Primers; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D011392:Proline; D000077288:Troglitazone; D000409:Alanine