Validity of the reduced-sample insulin modified frequently-sampled intravenous glucose tolerance test using the nonlinear regression approach

Abstract

The disposition index, the product of the insulin sensitivity index (SI) and the acute insulin response to glucose, is linked in African Americans to chromosome 11q. This link was determined with SI calculated with the nonlinear regression approach to the minimal model and data from the reduced-sample insulin-modified frequently-sampled intravenous glucose tolerance test (Reduced-Sample-IM-FSIGT). However, the application of the nonlinear regression approach to calculate SI using data from the Reduced-Sample-IM-FSIGT has been challenged as being not only inaccurate but also having a high failure rate in insulin-resistant subjects. Our goal was to determine the accuracy and failure rate of the Reduced-Sample-IM-FSIGT using the nonlinear regression approach to the minimal model. With SI from the Full-Sample-IM-FSIGT considered the standard and using the nonlinear regression approach to the minimal model, we compared the agreement between SI from the Full- and Reduced-Sample-IM-FSIGT protocols. One hundred African Americans (body mass index, 31.3 ± 7.6 kg/m2 [mean ± SD]; range, 19.0-56.9 kg/m2) had FSIGTs. Glucose (0.3 g/kg) was given at baseline. Insulin was infused from 20 to 25 minutes (total insulin dose, 0.02 U/kg). For the Full-Sample-IM-FSIGT, SI was calculated based on the glucose and insulin samples taken at −1, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 minutes. For the Reduced-Sample-FSIGT, SI was calculated based on the time points that appear in bold. Agreement was determined by Spearman correlation, concordance, and the Bland-Altman method. In addition, for both protocols, the population was divided into tertiles of SI. Insulin resistance was defined by the lowest tertile of SI from the Full-Sample-IM-FSIGT. The distribution of subjects across tertiles was compared by rank order and κ statistic. We found that the rate of failure of resolution of SI by the Reduced-Sample-IM-FSIGT was 3% (3/100). For the remaining 97 subjects, SI for the Full- and Reduced-Sample-IM-FSIGTs were as follows: 3.76 ± 2.41 L mU−1 min−1 (range, 0.58-14.50) and 4.29 ± 2.89 L mU−1 min−1 (range, 0.52-14.42); relative error, 21% ± 18%; Spearman r = 0.97; and concordance, 0.94 (both P < .001). After log transformation, the Bland-Altman limits of agreement were −0.29 and 0.53. The exact agreement for distribution of the population in the insulin-resistant tertile vs the insulin-sensitive tertiles was 92%, κ of 0.82 ± 0.06. Using the nonlinear regression approach and data from the Reduced-Sample-IM-FSIGT in subjects with a wide range of insulin sensitivity, failure to resolve SI occurred in only 3% of subjects. The agreement and maintenance of rank order of SI between protocols support the use of the nonlinear regression approach to the minimal model and the Reduced-Sample-IM-FSIGT in clinical studies.