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.

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.

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.

Trial registration: ClinicalTrials.gov NCT00220961.

Figures

Figure 1.

Baseline (left panels) and change at closeout (right panels) values for the Matsuda index (top panels) and Quantose MQ (bottom panels) according to glucose tolerance status at closeout in subjects randomized to pioglitazone or placebo. Plots are mean + 95% CIs. #, P = .008 for the difference between NGT and IGT/T2D; *, P < .01 for the difference between NGT and IGT/T2D; and §, P < .01 for the difference between pioglitazone and placebo by two-way ANOVA.

Figure 2.

Relationship between closeout changes in Quantose MQ and the Matsuda index in subjects randomized to pioglitazone or placebo. The best fit is linear in both groups (r = 0.69, P < .0001, for pioglitazone; and r = 0.77, P < .0001, for placebo); the fitted line for the pioglitazone group is significantly (P = .01) different from that of the placebo group.