title: Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates.
abstract: We examined the metabolic characteristics that attend the development of type 2 diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated in the ACT NOW Study and had complete end-of-study metabolic measurements. Subjects were randomized to receive pioglitazone (PGZ; 45 mg/day) or placebo and were observed for a median of 2.4 years. Indices of insulin sensitivity (Matsuda index [MI]), insulin secretion (IS)/insulin resistance (IR; ΔI0-120/ΔG0-120, ΔIS rate [ISR]0-120/ΔG0-120), and β-cell function (ΔI/ΔG × MI and ΔISR/ΔG × MI) were calculated from plasma glucose, insulin, and C-peptide concentrations during oral glucose tolerance tests at baseline and study end. Diabetes developed in 45 placebo-treated vs. 15 PGZ-treated subjects (odds ratio [OR] 0.28 [95% CI 0.15-0.49]; P < 0.0001); 48% of PGZ-treated subjects reverted to normal glucose tolerance (NGT) versus 28% of placebo-treated subjects (P < 0.005). Higher final glucose tolerance status (NGT > IGT > T2DM) was associated with improvements in insulin sensitivity (OR 0.61 [95% CI 0.54-0.80]), IS (OR 0.61 [95% CI 0.50-0.75]), and β-cell function (ln IS/IR index and ln ISR/IR index) (OR 0.26 [95% CI 0.19-0.37]; all P < 0.0001). Of the factors measured, improved β-cell function was most closely associated with final glucose tolerance status.
authors.affiliation: Texas Diabetes Institute, San Antonio, Texas.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Defronzo
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Schwenke
authors.forename: Maryann
authors.initials: M
authors.lastname: Banerji
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Clement
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.forename: Abbas E
authors.initials: AE
authors.lastname: Kitabchi
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ratner
authors.forename: Frankie B
authors.initials: FB
authors.lastname: Stentz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D005260:Female; D018149:Glucose Intolerance / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone