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. 2017 Jul 19;5(1):e000415.
doi: 10.1136/bmjdrc-2017-000415. eCollection 2017.

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

Ibiye Owei  1 , Nkiru Umekwe  1 , Casey Provo  1 , Jim Wan  2 , Samuel Dagogo-Jack  1
Affiliations

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

Ibiye Owei et al. BMJ Open Diabetes Res Care. .

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±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.

Keywords: cardiovascular disease risk; ethnic comparisons; obesity metabolism; pre-diabetes.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Upper panel: Regression plots of insulin sensitivity (Si-clamp) (A) and homeostasis model of insulin resistance (HOMA-IR) (B) versus body mass index, and Si-clamp versus HOMA-IR (C), in African Americans (closed circles) and European Americans (open circles). Lower panel: Percentile distribution of Si-clamp (D) and HOMA-IR (E) in the study cohort. HOMA-IR data were obtained in 320 subjects, of whom 206 underwent hyperinsulinemic euglycemic clamp to generate Si-clamp data.
Figure 2
Figure 2
Insulin sensitivity (Si-clamp) in obese and non-obese study subjects (A) and cumulative incidence of pre-diabetes/type 2 diabetes in insulin-resistant obese (IRO), insulin-sensitive obese (ISO), insulin-resistant non-obese (IRN) and insulin-sensitive non-obese (ISN) subjects (B). The cumulative incidence was 48.7% in IRO, 30.9% in ISO, 47.1% in IRN and 26% in ISN groups, respectively (χ2 P for trend=0.0024). (C) Kaplan-Meier plot of pre-diabetes/type 2 diabetes survival among participants stratified by IRO, IRN, ISO or ISN status (log-rank sum p=0.0001).
See this image and copyright information in PMC

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