Haptoglobin phenotype and levels in type 2 diabetes and effects of fenofibrate

Abstract

Aims/Hypothesis: In diabetes haptoglobin (Hp) 2 vs Hp 1 allelic product is associated with cardiac and renal complications. Few studies report both Hp phenotype and Hp levels. In a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial substudy we evaluated the Hp phenotype, Hp levels, and fenofibrate effects. Materials and Methods: In 480 adults with type 2 diabetes (T2D) the Hp phenotype was assessed and the Hp level quantified (both using ELISAs assays) in plasma from baseline, after 6 weeks of fenofibrate, and (in n = 200) at 2 years post-randomization to fenofibrate or placebo. Results: The Hp phenotypes 1-1, 2-1, and 2-2 frequencies were 15%, 49%, and 36%, respectively. Baseline Hp levels differed by phenotype (P < 0.0001) and decreased (median 21%) after 6 weeks fenofibrate in all phenotypes (adjusted mean (95% CI): −0.27 (−0.32, −0.23) mg/mL in Hp 1-1, −0.29 (−0.31, −0.27) mg/mL in Hp 2-1 and −0.05 (−0.07, −0.02) mg/mL in Hp 2-2 (P = 0.005 and P = 0.055 vs Hp 1-1 and Hp 2-1, respectively)). At 2 years post-randomization the Hp levels in the placebo group had returned to baseline, whilst the fenofibrate-group levels remained similar to the 6 week levels. Conclusions: In type 2 diabetes, Hp levels differ by Hp phenotype and are decreased by fenofibrate in all phenotypes, but the effect is diminished in Hp 2-2.