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

Devjit Tripathy, Jeff E. Cobb, Walter Gall, Klaus Peter Adam, Tabitha George, Dawn C. Schwenke, Mary Ann Banerji, George A. Bray, Thomas A. Buchanan, Stephen C. Clement, Robert R. Henry, Abbas E. Kitabchi, Sunder Mudaliar, Robert E. Ratner, Frankie B. Stentz, Peter D. Reaven, Nicolas Musi, Ele Ferrannini, Ralph A. DeFronzo

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective: The objective was to test the clinical utility of Quantose MQ to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose MQ is derived from fasting measurements of insulin, α-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 MQ 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 MQ 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 MQ outperformed both Matsuda and fasting insulin in predicting incident diabetes. Conclusions: In IGT subjects, Quantose MQ 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 MQ may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.

Original languageEnglish (US)
Pages (from-to)1855-1862
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number5
DOIs
StatePublished - May 1 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Tripathy, D., Cobb, J. E., Gall, W., Adam, K. P., George, T., Schwenke, D. C., Banerji, M. A., Bray, G. A., Buchanan, T. A., Clement, S. C., Henry, R. R., Kitabchi, A. E., Mudaliar, S., Ratner, R. E., Stentz, F. B., Reaven, P. D., Musi, N., Ferrannini, E., & DeFronzo, R. A. (2015). A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: The ACT NOW study. Journal of Clinical Endocrinology and Metabolism, 100(5), 1855-1862. https://doi.org/10.1210/jc.2014-3824