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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.
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1 Maastricht Centre for Systems Biology (MACSBIO), Maastricht University, Maastricht, The Netherlands
2 Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
3 Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
4 Department of Epidemiology, Maastricht University, Maastricht, The Netherlands
5 Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; Heart and Vascular Center, Maastricht University Medical Center+, Maastricht, The Netherlands
6 Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands; Department of Rehabilitation Medicine, Maastricht University, Maastricht, The Netherlands
7 Maastricht Centre for Systems Biology (MACSBIO), Maastricht University, Maastricht, The Netherlands; Department of Data Science & Knowledge Engineering, Maastricht University, Maastricht, The Netherlands
8 Maastricht Centre for Systems Biology (MACSBIO), Maastricht University, Maastricht, The Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
9 Maastricht Centre for Systems Biology (MACSBIO), Maastricht University, Maastricht, The Netherlands; Department of Toxicogenomics, GROW School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
10 Maastricht Centre for Systems Biology (MACSBIO), Maastricht University, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; Department of Epidemiology, Maastricht University, Maastricht, The Netherlands