513-P: Sustained Reduction of Atherogenic Lipoproteins Two Years after Modest Weight Loss in the POUNDS Lost Trial

Apolipoprotein C-III (ApoC3) delays clearance of VLDL and LDL. Lipoprotein subspecies that contain ApoC3 are most predictive of CHD in type 2 diabetes. Our study's objective was to determine if diet-induced weight loss would reduce the concentration of atherogenic lipoproteins including ApoC3.

Methods: The POUNDS LOST trial was a two-year interventional study where 811 participants were randomized into four diet groups with varying macronutrient compositions. Standard lipid panels were performed at 0, 6, and 24 months. Lipoprotein subspecies by ApoC3 content and density (VLDL, LDL & HDL) were analyzed for ApoC3, ApoB, ApoE, triglyceride and cholesterol concentrations at baseline and 24 months on ~100 samples in each diet group (age 53 ± 9 y, BMI 32 ± 4 kg/m2, 60% female). Samples. Data were analyzed utilizing STATA software to perform non-parametric tests and multivariate regression models on lipoprotein subspecies.

Results: On average, participants lost 7% of the baseline weight at 6 months and 5% at 24 months. There were significant reductions in total cholesterol (-10.4±26 mg/dL, p<0.001), LDL-C (-5.7± 23 mg/dL, p=0.004), non-HDL-C (-11.4 ± 24 mg/dL, p<0.001), and triglyceride (TG) (-31.6 ± 59 mg/dL, p<0.001) as well as an increase in HDL-C (1.2± 7 mg/dL, p=0.02) at 6 months. The reduction in non-HDL-C and TG remained significant at 24 months, but changes in LDL-C, HDL-C or total cholesterol did not. At 24 months, despite an average 1.6% weight regain, plasma concentration of ApoC3 in LDL (p=0.02), HDL (p=0.03), and VLDL (p < 0.001) remained lower than baseline. Weight change (0-24 months) was positively associated with changes in ApoC3 level independent of age, sex, race, BMI, and dietary assignment (r=0.03, p=0.002).

Conclusion: Even modest weight loss reduces the concentration of atherogenic lipoproteins and increases the protective lipoprotein concentrations in individuals who were overweight or obese. These effects appear sustainable despite weight regain.