title: A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.
abstract: OBJECTIVE
  The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal.
  
  
  METHODS
  Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained.
  
  
  RESULTS
  Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose M(Q) increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min(-1)·kgwbm(-1)) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose M(Q) correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose M(Q) outperformed both Matsuda and fasting insulin in predicting incident diabetes.
  
  
  CONCLUSIONS
  In IGT subjects, Quantose M(Q) parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose M(Q) may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.
authors.affiliation: Texas Diabetes Institute (D.T., N.M., R.A.D.), University of Texas Health Science Center, San Antonio, Texas 78207; South Texas Veterans Health Care System (D.T., N.M., R.A.D.), Audie L. Murphy Division, San Antonio, Texas 78228; Metabolon, Inc (J.E.C., W.G., K.-P.A., T.G.), Durham, North Carolina 27713; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing and Health Care Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85004; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center/Louisiana State University (G.A.B.), Baton Rouge, Louisiana 70808; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California 90033; VA San Diego Healthcare System and University of California at San Diego (R.R.H., S.M.), San Diego, California 92161; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee, Memphis, Tennessee 38163; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782; and Department of Clinical and Experimental Medicine (E.F.), CNR Institute of Clinical Physiology, 56126 Pisa, Italy.
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.forename: Jeff E
authors.initials: JE
authors.lastname: Cobb
authors.forename: Walter
authors.initials: W
authors.lastname: Gall
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Adam
authors.forename: Tabitha
authors.initials: T
authors.lastname: George
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: 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: Peter D
authors.initials: PD
authors.lastname: Reaven
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D018149:Glucose Intolerance / Q000175:diagnosis* / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011236:Prediabetic State / Q000188:drug therapy* / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone