Relationships of adipocyte-fatty acid binding protein and lipocalin 2 with risk factors and chronic complications in type 2 diabetes and effects of fenofibrate: A fenofibrate Intervention and event lowering in diabetes sub-study

Abstract

Aims: To investigate determinants of circulating levels of adipocyte-fatty acid binding protein (A-FABP) and lipocalin-2 (LCN2), their relationships with cardiovascular disease (CVD) and microvascular events, and effects of fenofibrate in type 2 diabetes (T2D).

Methods: A-FABP and LCN2 were quantified in baseline plasma from 2000 T2D adults in a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial sub-study and correlates thereof determined. In a subset (n = 200) adipokines were also measured on-trial.

Results: Female sex, older age, higher body mass index (BMI), HbA1c, insulin resistance index, triglycerides, plasma creatinine and homocysteine, shorter diabetes duration, and use of oral hypoglycaemic agents alone were independent determinants of higher A-FABP. Higher BMI, fibrinogen and homocysteine, Caucasian race, and lower fasting glucose, HDL-cholesterol, apolipoprotein A-II and estimated glomerular filtration rate were independent predictors of higher LCN2 levels. Baseline A-FABP and LCN2 levels were associated with multiple new CVD and microvascular events over 5-years, though significance was lost after risk factor adjustment. Fenofibrate increased A-FABP but did not change LCN2 levels.

Conclusions: Baseline plasma A-FABP and LCN2 levels were associated with concurrent CVD risk factors, and on-trial chronic complications, likely mediated via traditional risk factors. Fenofibrate increased A-FABP modestly but did not affect LCN2 levels.

Clinical trial registration: ISRCTN 64783481.

Keywords: Adipocyte-fatty acid binding protein; Adipokine; Cardiovascular outcome; Fenofibrate; Lipocalin-2; Microvascular disease.