Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

Abstract

Objectives: Bilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM).

Design and methods: Plasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects.

Results: Triglycerides, large VLDL, small LDL and small HDL particles were increased (all p<0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p<0.05), coinciding lower bilirubin levels in T2DM (p<0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p<0.05 to p<0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p<0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p<0.05).

Conclusions: Increased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.

Keywords: Apolipoprotein E; Bilirubin; Lipoprotein subfractions; Low density lipoproteins; Nuclear magnetic resonance spectroscopy; Triglycerides; Type 2 diabetes mellitus; Very low density lipoproteins.