Levels of the soluble LDL receptor-relative LR11 decrease in overweight individuals with type 2 diabetes upon diet-induced weight loss.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is a major complication in patients with type 2 diabetes (T2D), especially in those with obesity. Plasma soluble low density lipoprotein receptor-relative with 11 ligand-binding repeats (sLR11) plays a role in the development of atherosclerosis and has been linked to the metabolism of triglyceride-rich lipoproteins, adiposity, and vascular complications in T2D. We aimed to determine the effect of diet-induced weight loss on plasma sLR11 levels in overweight and obese individuals with T2D. METHODS: Plasma sLR11 levels were determined in 64 individuals with T2D and BMI >27 kg/m2 before and after a 20-week weight loss diet. As a reference, sLR11 levels were also determined in 64 healthy, non-obese controls, matched as a group for age and sex. RESULTS: Median plasma sLR11 levels of the T2D study-group at baseline (15.4 ng/mL (IQR 12.9-19.5)) were higher than in controls (10.2 (IQR: 8.7-12.2) ng/mL; p = 0.001). The diet resulted in a weight loss of 9.7 ± 5.2% (p = 0.001) and improved CVD risk factors. sLR11 levels were reduced to 13.3 ng/mL (IQR 11.0-17.1; p = 0.001). Changes in sLR11 levels positively associated with changes in non-HDL cholesterol (B = 1.54, R2 = 0.17, p = 0.001) and HbA1c (B = 0.07, R2 = 0.11, p = 0.007), but not with weight loss (B = 0.04, R2 = 0.05, p = 0.076). The changes in non-HDL cholesterol and HbA1c together explained 24% of the variance of sLR11 reduction (p = 0.001). CONCLUSIONS: Weight loss dieting in overweight and obese individuals with T2D resulted in a reduction in plasma sLR11 levels that was associated with improvements in lipid-profile and glycemic state.