Resting Whole Body Energy Metabolism in Class 3 Obesity; from Preserved Insulin Sensitivity to Overt Type 2 Diabetes

Context: Insulin resistance and diabetes may influence separately or in combination whole body energy metabolism. Objective: To assess the impact of insulin resistance and/or overt type 2 diabetes on resting energy expenditure (REE) in class 3 obese individuals. Design and Setting: Retrospective, cross-sectional analysis of a set of data about individuals attending the outpatients service of a single center of bariatric surgery between January 2015 and December 2017. Patients: We screened 382 patients in which abnormal thyroid function was excluded, and segregated them in three groups of subjects: patients with type 2 diabetes (T2DM; n=70), non-diabetic insulin-resistant patients with HOMA-IR ≥ 3 (n=236), non-diabetic insulin-sensitive patients with HOMA-IR < 3 (n=75). Main Outcome Measure: Resting energy expenditure (REE), body composition and insulin resistance assessed using indirect calorimetry, bioimpedance and HOMA-IR. Results: Non-diabetic insulin-sensitive patients resulted to be younger, with lower BMI and higher prevalence of female subjects; meanwhile, non-diabetic but insulin-resistant patients and T2DM patients were not different in terms of anthropometric parameters. REE was higher in T2DM than in non-diabetic insulin-resistant and insulin-sensitive individuals when expressed as percent of the predicted REE (based on Harris Benedict equation) (p<0.0001) or when adjusted for kg of free fat mass (p<0.0001) and was found to be higher also in insulin-resistant vs insulin-sensitive patients (p<0.001). The respiratory quotient was different between groups (0.87±0.11, 0.86±0.12 and 0.91±0.14 in T2DM, insulin-resistant and insulin-sensitive patients, respectively; p<0.03). Regression analysis confirmed that HOMA-IR was independently associated with the REE (R2=0.110, p<0.001). Conclusion: Class 3 obese patients with normal insulin sensitivity are characterized by reduced fasting REE in comparison to insulin-resistant obese patients and obese patients with short duration of diabetes supporting the hypothesis that down-regulation of nutrients’ oxidative disposal may represent an adaptation of energy metabolism in obese individuals with preserved insulin sensitivity.