@article {Oweie000415, author = {Ibiye Owei and Nkiru Umekwe and Casey Provo and Jim Wan and Samuel Dagogo-Jack}, title = {Insulin-sensitive and insulin-resistant obese and non-obese phenotypes: role in prediction of incident pre-diabetes in a longitudinal biracial cohort}, volume = {5}, number = {1}, elocation-id = {e000415}, year = {2017}, doi = {10.1136/bmjdrc-2017-000415}, publisher = {BMJ Specialist Journals}, abstract = {Objective We 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 methods 320 healthy subjects (176 AA, 144 EA; mean age 44.2{\textpm}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.Results Compared 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).Conclusions Insulin 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.}, URL = {https://drc.bmj.com/content/5/1/e000415}, eprint = {https://drc.bmj.com/content/5/1/e000415.full.pdf}, journal = {BMJ Open Diabetes Research and Care} }