HDL particle size is increased and HDL-cholesterol efflux is enhanced in type 1 diabetes: a cross-sectional study

Aims/hypothesis The prevalence of atherosclerosis is increased in type 1 diabetes despite normal-to-high HDL-cholesterol levels. The cholesterol efflux capacity (CEC) of HDL is a better predictor of cardiovascular events than static HDL-cholesterol. This cross-sectional study addressed the hypothesis that impaired HDL function contributes to enhanced CVD risk within type 1 diabetes. Methods We compared HDL particle size and concentration (by NMR), total CEC, ATP-binding cassette subfamily A, member 1 (ABCA1)-dependent CEC and ABCA1-independent CEC (by determining [H-3]cholesterol efflux from J774-macrophages to ApoB-depleted serum), and carotid intima-media thickness (CIMT) in 100 individuals with type 1 diabetes (37.6 +/- 1.2 years; BMI 26.9 +/- 0.5 kg/m(2)) and 100 non-diabetic participants (37.7 +/- 1.1 years; 27.1 +/- 0.5 kg/m(2)). Results Compared with non-diabetic participants, total HDL particle concentration was lower (mean +/- SD 31.01 +/- 8.66 vs 34.33 +/- 8.04 mu mol/l [mean difference (MD) -3.32 mu mol/l]) in participants with type 1 diabetes. However, large HDL particle concentration was greater (9.36 +/- 3.98 vs 6.99 +/- 4.05 mu mol/l [MD +2.37 mu mol/l]), resulting in increased mean HDL particle size (9.82 +/- 0.57 vs 9.44 +/- 0.56 nm [MD +0.38 nm]) (p < 0.05 for all). Total CEC (14.57 +/- 2.47%CEC/4 h vs 12.26 +/- 3.81%CEC/4 h [MD +2.31%CEC/4 h]) was greater in participants with type 1 diabetes relative to non-diabetic participants. Increased HDL particle size was independently associated with increased total CEC; however, following adjustment for this in multivariable analysis, CEC remained greater in participants with type 1 diabetes. Both components of CEC, ABCA1-dependent (6.10 +/- 2.41%CEC/4 h vs 5.22 +/- 2.57%CEC/4 h [MD +0.88%CEC/4 h]) and ABCA1-independent (8.47 +/- 1.79% CEC/4 h vs 7.05 +/- 1.76% CEC/4 h [MD +1.42% CEC/4 h]) CEC, were greater in type 1 diabetes but the increase in ABCA1-dependent CEC was less marked and not statistically significant in multivariable analysis. CIMT was increased in participants with type 1 diabetes but in multivariable analysis it was only associated negatively with age and BMI. Conclusions/interpretation HDL particle size but not HDL-cholesterol level is independently associated with enhanced total CEC. HDL particle size is greater in individuals with type 1 diabetes but even after adjusting for this, total and ABCA1-independent CEC are enhanced in type 1 diabetes. Further studies are needed to understand the mechanisms underlying these effects, and whether they help attenuate progression of atherosclerosis in this high-risk group.

Automated summary

The size of HDL particles, rather than the level of HDL-cholesterol, is independently associated with enhanced total CEC. Individuals with type 1 diabetes have larger HDL particle size, but even after adjustment, total and ABCA1-independent CEC are increased in type 1 diabetes.