Introduction: Type 2 diabetes (T2D) is a multifactorial disease with both heritable and environmental origins. Overweight and obesity are the primary risk factors, present in 90% of persons with T2D. However, little is known of the intrinsic risk carried by individuals with moderate to severe obesity. The purpose of this study was to identify and analyze risk factors in obese individuals with and without clinical metabolic risk factors. We hypothesized that the insulin sensitivity of metabolically healthy obese individuals would be similar to their BMI matched counterparts.
Methods: Eighty-seven sedentary adults underwent an inpatient stay consisting of anthropometric measurements, blood chemistries, body composition (DXA), aerobic capacity (VO2MAX), and insulin sensitivity testing (glucose clamp). Subjects were first stratified by BMI (<25 and >30). Those with a BMI >30 were further stratified based upon a composite metabolic health score consisting of: BMI, VO2MAX, HOMA-IR, triglycerides, and cholesterol levels. Group differences were assessed using a one-way ANOVA with multiple comparisons.
Results: Individuals with obesity had elevated HDL, LDL, blood pressure, waist-to-hip ratio and body fat (ALL P<0.05) compared to lean controls, with no differences between metabolically healthy and unhealthy individuals. Metabolically unhealthy individuals had elevated fasting insulin (P<0.05) and glucose (P<0.05) levels compared to both lean controls and metabolically healthy obese individuals. However, both the metabolically healthy and unhealthy obese individuals had reduced insulin sensitivity (lean to obese P<0.01, interaction P=0.40) compared to lean controls.
Conclusions: Metabolically healthy obese individuals retain the risk associated with T2D, most notable being reduced insulin sensitivity. Furthermore, we posit that safe and effective treatments for T2D, such as insulin sensitizing therapy or bariatric surgery, may be warranted in metabolically healthy obese individuals alike.
C.L. Axelrod: None. A. Hari: None. J.T. Mey: None. R.A. Beyl: None. J.P. Kirwan: None.
National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; Louisiana Clinical & Translational Science Center