Endocrine Abstracts

Background: Hypocaloric diets reduce the risk for type 2 diabetes (T2D) in obese subjects. However, there is a large inter-subject variability in the response to these interventions. The factors affecting this variability remain poorly understood. We and others reported that high plasma apoB-lipoproteins predict risk factors for, and incidence of, T2D in obese subjects independent of adiposity or fat distribution.

Objective: To test the hypothesis that plasma apoB predicts the response to hypocaloric diet in reducing risk factors for T2D, namely white adipose tissue (WAT) dysfunction, insulin resistance and hyperinsulinemia.

Methods: Obese subjects were assessed before and after a 6-months hypocaloric intervention (58±6 years, 32.6±4.6 kg/m²). Insulin secretion and sensitivity were measured using a Botnia clamp (N=59). Ex vivo gynoid WAT function was measured in a subpopulation of 22 subjects as the hydrolysis and storage of ³H-triolein-labeled-triglyceride-rich-lipoproteins in WAT biopsies.

Results: Following the intervention, subjects in the highest tertile of baseline plasma apoB (9 men and 10 women, apoB=1.04–1.80 g/l) had an improvement in insulin sensitivity (HOMA-IR=−26.9% and M/I_clamp=+57.3%) and a decrease in total glucose-induced-insulin secretion (−33.8%, P=0.001 for all). However, despite equal weight loss (~ 6%), subjects in the lowest plasma apoB tertile (0.34–0.85 g/l) had no such benefits. Moreover, only subjects above median apoB (0.99 g/l) increased WAT function (+105.3%, P=0.041). Finally, among subjects with high plasma apoB, those who decreased plasma apoB had a better post-weight loss insulin sensitivity than those who did not (M/I_clamp=0.061±0.004 vs 0.045±0.006 mg/kg⁻¹.min⁻¹/uU/ml, P=0.034). Plasma apoB was not correlated with body weight or composition at baseline or following weight-loss.

Conclusions: Plasma apoB predicts the improvement in risk factors for T2D in response to hypocaloric diets. We propose that targeting subjects with hyperapoB reduce the risk for T2D maximally in an obese population.