Improved quantification of muscle insulin sensitivity using oral glucose tolerance test data: the MISI Calculator

Shauna D O’Donovan,Michael Lenz,Marleen M Van Greevenbroek,Natal A W Van Riel,Gijs H Goossens,Simone J M P Eussen,Carla J H Van Der Kallen,Ilja C W Arts,Coen D A Stehouwer,Miranda T Schram,Ralf L M Peeters,Theo M C M De Kok,Simone J Sep,Ellen E Blaak

doi:10.1038/s41598-019-45858-w

Shauna D O’Donovan, Michael Lenz + Show 12 more

Open Access

https://doi.org/10.1038/s41598-019-45858-w

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Abstract

The Muscle Insulin Sensitivity Index (MISI) has been developed to estimate muscle-specific insulin sensitivity based on oral glucose tolerance test (OGTT) data. To date, the score has been implemented with considerable variation in literature and initial positive evaluations were not reproduced in subsequent studies. In this study, we investigate the computation of MISI on oral OGTT data with differing sampling schedules and aim to standardise and improve its calculation. Seven time point OGTT data for 2631 individuals from the Maastricht Study and seven time point OGTT data combined with a hyperinsulinemic-euglycaemic clamp for 71 individuals from the PRESERVE Study were used to evaluate the performance of MISI. MISI was computed on subsets of OGTT data representing four and five time point sampling schedules to determine minimal requirements for accurate computation of the score. A modified MISI computed on cubic splines of the measured data, resulting in improved identification of glucose peak and nadir, was compared with the original method yielding an increased correlation (ρ = 0.576) with the clamp measurement of peripheral insulin sensitivity as compared to the original method (ρ = 0.513). Finally, a standalone MISI calculator was developed allowing for a standardised method of calculation using both the original and improved methods.

Highlights

Insulin resistance is an important feature of the metabolic syndrome, which has been associated with approximately a threefold increased risk for the development of type 2 diabetes mellitus and cardiovascular disease[1]
Had the Oral Glucose Tolerance Test (OGTT) been sampled at just five time points (t0, 30, 60, 90, 120 min) (Fig. 1b, black bars), the majority of individuals with a peak glucose at 45 min would be distributed between having a glucose peak at 30 min (366 of 722 individuals) or 60 min (324 of 722 individuals)
Insulin resistance is often present in multiple tissues long before the onset of overt clinical disorders such as type 2 diabetes mellitus and cardio-vascular diseases

Summary

Introduction

Insulin resistance is an important feature of the metabolic syndrome, which has been associated with approximately a threefold increased risk for the development of type 2 diabetes mellitus and cardiovascular disease[1]. This approach was repeated www.nature.com/scientificreports within the PRESERVE Study data set (n = 71), comparing the MISI computed using both methods on five time point and the various four time point subsets to the ssGIR of the hyperinsulinemic-euglycaemic clamp.

Results

Conclusion