title: Diabetes Incidence and Glucose Tolerance after Termination of Pioglitazone Therapy: Results from ACT NOW.
abstract: Thiazolidinediones have proven efficacy in preventing diabetes in high-risk individuals. However, the effect of thiazolidinediones on glucose tolerance after cessation of therapy is unclear.
  
  
  
  To examine the effect of pioglitazone (PIO) on incidence of diabetes after discontinuing therapy in ACT NOW. Design, Settings and Patients: Two-hundred ninety-three subjects (placebo [PLAC], n = 138; PIO, n = 152) completed a median followup of 11.7 mo after study medication was stopped.
  
  
  
  Diabetes developed in 138 (12.3%) of PLAC vs 17 of 152 PIO patients (11.2%; P = not significant, PIO vs PLAC). However, the cumulative incidence of diabetes from start of study medication to end of washout period remained significantly lower in PIO vs PLAC (10.7 vs 22.3%; P < .005). After therapy was discontinued, 23.0% (35/152) of PIO-treated patients remained normal-glucose tolerant (NGT) vs 13.8% (19/138) of PLAC-treated patients (P = .04). Insulin secretion/insulin resistance index (I0-120/G0-120 × Matsuda index) was markedly lower in subjects with impaired glucose tolerance (IGT) who converted to diabetes during followup vs those who remained IGT or NGT. The decline in-cell function (insulin secretion/insulin resistance index) was similar in subjects with IGT who developed diabetes, irrespective of whether they were treated with PIO or PLAC.
  
  
  
  1) The protective effect of PIO on incidence of diabetes attenuates after discontinuation of therapy, 2) cumulative incidence of diabetes in individuals exposed to PIO remained significantly (56%) lower than PLAC and a greater number of PIO-treated individuals maintained NGT after median followup of 11.4 mo, and 3) low insulin secretion/insulin resistance index is a strong predictor of future diabetes following PIO discontinuation.
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Schwenke
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: MaryAnn
authors.initials: M
authors.lastname: Banerji
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Clement
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Abbas E
authors.initials: AE
authors.lastname: Kitabchi
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ratner
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Frankie B
authors.initials: FB
authors.lastname: Stentz
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D015994:Incidence; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology*; D045162:Thiazolidinediones / Q000009:adverse effects*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone