Insulin resistance persists despite a metabolically healthy obesity phenotype

Abstract

Objective: Metabolically healthy obesity (MHO) is often defined as the absence of metabolic syndrome in the presence of obesity. However, phenotypic features of MHO are unclear. Insulin sensitivity in MHO was cross-sectionally compared with metabolically unhealthy obesity (MUO) and a reference group of young healthy participants without obesity.

Methods: Sedentary adults (n = 96) undergoing anthropometric, blood chemistries, maximal aerobic capacity, and euglycemic-hyperinsulinemic clamp measurements were classified by BMI (<25 and ≥30 kg/m2 ). MUO was defined as having obesity with metabolic syndrome (≥2 additional risk factors). Data were analyzed using a linear mixed models approach.

Results: Body weight was similar between MHO and MUO. Body fat (percentage) and high-density lipoprotein cholesterol were higher (p < 0.001), and systolic blood pressure, triglycerides, glucose, and insulin were lower in MHO versus MUO (p < 0.03, all). The MHO group also had lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol, diastolic blood pressure, and insulin compared with the reference. Both the MHO and MUO groups displayed impaired insulin sensitivity compared with the reference control (p < 0.001).

Conclusions: Participants with MHO had distinct clinical measures related to hypertension, lipid metabolism, and glycemic control compared with a healthy reference group. Peripheral insulin resistance in obesity independent of metabolic status portends increased risk for type 2 diabetes in the MHO patient population.

Conflict of interest statement

CONFLICT OF INTEREST

At the time of publication, KKH will be employed by Abbott Laboratories. Abbott was not involved in design, analysis, interpretation, or funding of the present work. The other authors declared no conflict of interest.

© 2021 The Obesity Society.

Figures

FIGURE 1

Participant classification. Those who previously completed metabolic inpatient stays were classified by BMI (2). Participants with a BMI ≥30 kg/m2 were identified as having MUO if they presented with two or more metabolic syndrome risk factor criteria, including hypertension (>130 mmHg systolic or > 85 mmHg diastolic), hyperglycemia (fasting glucose ≥100 mg/dL), triglycerides (≥150 mg/dL), and HDL cholesterol (<40 mg/dL [men] or <50 mg/dL [women]). There was no overall statistical difference observed for biological sex (p = 0.694). MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity

FIGURE 2

Comparison of whole body insulin sensitivity relative to total mass in each phenotype. Comparison of insulin sensitivity relative to total body mass in the healthy reference group (REF), MHO, and MUO. (A) Insulin-stimulated glucose disposal (GDR) (n = 94) and (B) insulin sensitivity relative to prevailing insulin concentrations (GDR/I) (n = 90). Data are displayed as a box (mean ± 95% CI) and whisker (minimum to maximum) plot. ****Denotes a significant (p < 0.001) difference relative to the healthy reference group. MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity