Insulin-sensitive and insulin-resistant obese and non-obese phenotypes: role in prediction of incident pre-diabetes in a longitudinal biracial cohort

Abstract

ObjectiveWe measured insulin sensitivity with euglycemic clamp (Si-clamp) in initially normoglycemic African Americans (AA) and European Americans (EA), to probe the existence of subphenotypes of obesity and leanness, and their impact on incident dysglycemia during longitudinal follow-up.Research design and methods320 healthy subjects (176 AA, 144 EA; mean age 44.2±10.6 years) underwent baseline assessments, including Si-clamp and homeostasis model of insulin resistance (HOMA-IR) and were stratified into: insulin-resistant obese (IRO) (body mass index (BMI) >30 kg/m2, Si-clamp <0.1, HOMA-IR >2.5); insulin-sensitive obesity (ISO) (BMI >30 kg/m2, Si-clamp >0.1, HOMA-IR <2.5); insulin-resistant non-obese (IRN) (BMI <28 kg/m2, Si-clamp <0.1, HOMA-IR >2.5); insulin-sensitive non-obese (ISN) (BMI <28 kg/m2, Si-clamp >0.1, HOMA-IR <2.5). Outcome measures were cardiometabolic risks and incident pre-diabetes/type 2 diabetes (T2D) during 5.5 years.ResultsCompared with IRO, subjects with ISO had lower abdominal fat, triglycerides and high-sensitivity C reactive protein and higher adiponectin (p=0.015 to <0.0001). IRN subjects had higher cardiometabolic risk markers than ISN (p=0.03 to <0.0001). During 5.5-year follow-up, incident pre-diabetes/T2D was lower in ISO (31.3% vs 48.7%) among obese subjects and higher in IRN (47.1% vs. 26.0%) among non-obese subjects (p=0.0024). Kaplan-Meier analysis showed significantly different pre-diabetes/T2D survival probabilities across insulin sensitivity/adiposity phenotypes (p=0.0001).ConclusionsInsulin sensitivity predicts ~40% decrease in the relative risk of incident pre-diabetes/T2D among obese persons, whereas insulin resistance predicts ~80% increased risk among non-obese persons. This is the first documentation of healthy and unhealthy phenotypes of obesity and leanness in a prospective biracial cohort, using rigorous measurement of insulin sensitivity.

The Metabolic Syndrome: Emerging Novel Insights Regarding the Relationship between the Homeostasis Model Assessment of Insulin Resistance and other Key Predictive Markers in Young Adults of Western Algeria

“…The HOMA-IR model is used to yield an estimate of insulin sensitivity and B-cell function from fasting plasma insulin and glucose concentrations. The present findings demonstrate that HbA1c, BMI and plasma TG are the sole among 12 variables to achieve, both in male and female MetS patients, a highly significant correlation with the HOMA-IR index is in fair agreement with some prior observations [14,[53][54][55]. In our opinion, this finding provides further support to the view that an altered regulation of plasma D-glucose and/or insulin concentration(s), as assessed by the HOMA-IR index, plays a key role in the non-enzymatic glycation of hemoglobin and regulation of plasma triglyceride concentration and coincides with the increase in BMI.…”

Beta-Cell Function, Self-rated Health, and Lifestyle Habits in 64-Year-Old Swedish Women with Metabolically Healthy Obesity Phenotype

“…The study population and study design have previously been extensively described elsewhere. 8 In brief, all 64-year-old women (n = 4,856) identified through the County Register in Gothenburg, Sweden, were sent an invitation letter to participate in a screening examination. Those who accepted (n = 2,893) completed a brief questionnaire that was enclosed with the letter.…”

“…6,7 However, preserved insulin sensitivity and paucity of the components of the MetS may characterize the MHO phenotype. 8 Physiologically, virtually all proinsulin molecules are cleaved into insulin and C-peptide. In healthy subjects, only a minor percentage of un-cleaved intact proinsulin is released into the circulation.…”

Lipids as risk markers for type 2 diabetes

“…The TG/HDL‐C ratio appears to be one of a number of useful lipid measurements indicative of visceral adiposity, and hence of insulin resistance. The TG level correlates strongly with clamp measurements of insulin sensitivity, which, in turn, is associated with visceral adiposity and T2D risk . In an analysis of 4398 adults in the 2011 to 2014 US National Health and Nutrition Examination Survey (NHANES), two simple measures of visceral adiposity, namely the supine sagittal abdominal diameter/height ratio and the WC/height ratio, correlated more strongly than BMI with fasting insulin, TGs, and with the TG/HDL‐C ratio .…”