A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

MedStar author(s):
Citation: Journal of Clinical Endocrinology & Metabolism. 100(5):1855-62, 2015 May.PMID: 25603459Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Randomized Controlled Trial | Research Support, N.I.H., ExtramuralSubject headings: *Blood Glucose/me [Metabolism] | *Diabetes Mellitus, Type 2/pc [Prevention & Control] | *Glucose Intolerance/di [Diagnosis] | *Hypoglycemic Agents/tu [Therapeutic Use] | *Insulin Resistance/ph [Physiology] | *Prediabetic State/dt [Drug Therapy] | *Thiazolidinediones/tu [Therapeutic Use] | Adult | Aged | Diabetes Mellitus, Type 2/me [Metabolism] | Female | Glucose Intolerance/me [Metabolism] | Glucose Tolerance Test | Humans | Insulin/bl [Blood] | Male | Middle Aged | Prediabetic State/me [Metabolism] | Treatment OutcomeYear: 2015Local holdings: Available online through MWHC library: 1999- June 2013, Available in print through MWHC library: 1999 - 2006ISSN:
  • 0021-972X
Name of journal: The Journal of clinical endocrinology and metabolismAbstract: 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.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, alpha-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal.RESEARCH DESIGN AND 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.All authors: Adam KP, Banerji M, Bray GA, Buchanan TA, Clement SC, Cobb JE, DeFronzo RA, Ferrannini E, Gall W, George T, Henry RR, Kitabchi AE, Mudaliar S, Musi N, Ratner RE, Reaven PD, Schwenke DC, Stentz FB, Tripathy DFiscal year: FY2015Digital Object Identifier: Date added to catalog: 2016-05-24
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 25603459 Available 25603459

Available online through MWHC library: 1999- June 2013, Available in print through MWHC library: 1999 - 2006

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.

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, alpha-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal.

RESEARCH DESIGN AND 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.

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