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

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.

Age-related susceptibility to insulin resistance is due to a combination of CPT1B decline and lipid overload

“…1J). The Muscle Insulin Sensitivity Index (MISI) estimates the rate of glucose removed per minute over average insulin concentration during the OGTT (24). Based on this parameter, the HFD acted on both age groups to lower the insulin sensitivity, which was further decreased in old animals (p age and p diet <0.0001) (Fig.…”

“…Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) indexes were calculated as previously described using both the fasting insulin and fasting glucose levels and corrected for mice (23). The Muscle Insulin Sensitivity Index (MISI) calculation was adapted from (24).…”

Current metabolic perspective on malnutrition in obesity: towards more subgroup-based nutritional approaches?

“…We addressed this question by characterising the plasma metabolome (15) and lipidome (16) and adipose tissue transcriptome profiles (17) in individuals with either more pronounced hepatic IR or more pronounced muscle IR in the European multicentre DIOGenes trial in overweight and obese individuals (18) ; and used the Cohort on Diabetes and Atherosclerosis Maastricht (19) and the Maastricht study, a large population-based cohort in the Maastricht area (20) as validation cohorts. Based on a 5 or 7-points oral glucose tolerance test with insulin and glucose concentrations we estimated hepatic IR and skeletal muscle insulin sensitivity indices (HIRI and MISI, respectively) as previously described and validated against a hyperinsulinemic clamp by Abdul Ghani et al (21) , and optimised for the MISI calculation by means of cubic splining by O'Donovan et al (22) . For descriptive purposes, we divided individuals in having no IR, having muscle IR (the lowest tertile of MISI), having hepatic IR (in the highest tertile of HIRI) or having both MISI and HIRI.…”

“…(21) , and optimised for the MISI calculation by means of cubic splining by O'Donovan et al . (22) . For descriptive purposes, we divided individuals in having no IR, having muscle IR (the lowest tertile of MISI), having hepatic IR (in the highest tertile of HIRI) or having both MISI and HIRI.…”

Insulin Signaling as a Key Moderator in Myotonic Dystrophy Type 1

“…It is well-established that those with insulin resistance have an increased prevalence of type 2 diabetes, and a 2–3 times higher risk for cardiovascular disease (107–110). Heart failure associated with type 2 diabetes results from impaired microvascular functioning and myocardial perfusion dysfunction (108).…”