title: Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.
abstract: To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm2). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.
authors: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78223, USA. espinozas2@uthscsa.edu.|Geriatrics Research, Education and Clinical Center, South Texas Veterans Health Care System, 7400 Merton Minter Blvd., San Antonio, TX, 78229, USA. espinozas2@uthscsa.edu.
authors: Sara E
authors: SE
authors: Espinoza
authors: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78223, USA.|Geriatrics Research, Education and Clinical Center, South Texas Veterans Health Care System, 7400 Merton Minter Blvd., San Antonio, TX, 78229, USA.
authors: Chen-Pin
authors: CP
authors: Wang
authors: Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.|South Texas Veterans Health Care System, 7400 Merton Minter Blvd., San Antonio, TX, 78229, USA.
authors: Devjit
authors: D
authors: Tripathy
authors: Department of Medicine Division of Endocrinology and Metabolism, Georgetown University, 3700 O St NW, Washington, DC, 20057, USA.
authors: Stephen C
authors: SC
authors: Clement
authors: Arizona State University, Tempe, AZ, 85281, USA.
authors: Dawn C
authors: DC
authors: Schwenke
authors: Department of Medicine Division of Endocrinology, State University of New York Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY, 11203, USA.
authors: Mary Ann
authors: MA
authors: Banerji
authors: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, 70803, USA.
authors: George A
authors: GA
authors: Bray
authors: Department of Medicine Division of Endocrinology and Diabetes, University of Southern California, Los Angeles, CA, USA.
authors: Thomas A
authors: TA
authors: Buchanan
authors: Department of Medicine Division of Endocrinology and Metabolism, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
authors: Robert R
authors: RR
authors: Henry
authors: Department of Medicine Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, 920 Court Ave, Memphis, TN, 38163, USA.
authors: Abbas E
authors: AE
authors: Kitabchi
authors: Department of Medicine Division of Endocrinology and Metabolism, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
authors: Sunder
authors: S
authors: Mudaliar
authors: Department of Medicine Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, 920 Court Ave, Memphis, TN, 38163, USA.
authors: Frankie B
authors: FB
authors: Stentz
authors: Phoenix Veterans Affairs Health Care System, 650 E Indian School Rd, Phoenix, AZ, 85012, USA.
authors: Peter D
authors: PD
authors: Reaven
authors: Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.|South Texas Veterans Health Care System, 7400 Merton Minter Blvd., San Antonio, TX, 78229, USA.
authors: Ralph A
authors: RA
authors: DeFronzo
authors: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78223, USA. musi@uthscsa.edu.|Geriatrics Research, Education and Clinical Center, South Texas Veterans Health Care System, 7400 Merton Minter Blvd., San Antonio, TX, 78229, USA. musi@uthscsa.edu.|Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA. musi@uthscsa.edu.
authors: Nicolas
authors: N
authors: Musi
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D053208:Kaplan-Meier Estimate; D008297:Male; D055442:Metabolome / Q000187:drug effects; D008875:Middle Aged; D000077205:Pioglitazone; D011236:Prediabetic State / Q000188:drug therapy*; D011897:Random Allocation; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054392:Adipokines; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Diabetes; Endocrinology; Geriatrics; Prevention