139-LB: Haptoglobin Phenotype and Levels in Type 2 Diabetes and Effects of Fenofibrate

Background: Haptoglobin (Hp) is a plasma protein with anti-oxidant, anti-inflammatory and pro-angiogenic properties. Based on the Hp gene alleles there are three Hp phenotypes (1-1, 2-1 and 2-2). In diabetes, Hp-2 is associated with substantially increased risk of cardiac and renal damage relative to Hp-1. AIMS: To evaluate 1) associations between Hp phenotype and levels; and 2) effects of fenofibrate vs. placebo on Hp levels.

Methods: A substudy of 180 adults with type 2 diabetes (T2D) (50% females) from the FIELD trial. Average age was 60±6 years, BMI 30.4±5.1 kg/m² and HbA1c 6.8±1.3%. Plasma (citrate) samples were evaluated at baseline, after 6-weeks daily 200 mg co-micronised fenofibrate (end of active run-in) and 2-years after randomisation to fenofibrate or placebo.

Results: Hp phenotype 1-1 was detected in 19%, Hp 2-1 in 48% and Hp 2-2 in 33% subjects. Hp levels at baseline were 1.44±1.10, 1.31±0.49 and 0.99±0.46 mg/mL in type 1-1, 2-1 and 2-2 respectively (all p<0.0001). In Hp type 2-2 baseline Hp levels correlated with HbA1c (r=0.35, p=0.005), BMI (r=0.30, p=0.02) and HDL-C (r=0.29, p=0.02). No such correlations were observed for Hp type 1-1 and 2-1. After 6-weeks fenofibrate Hp levels dropped by 22.3, 19.9 and 17.7% in type 1-1. 2-1 and 2-2 respectively (all p<0.0001; difference between types p=ns.). After 2-years of fenofibrate vs. placebo Hp levels in the placebo group had increased back to baseline values whereas Hp levels in the fenofibrate group remained reduced similar to 6-weeks levels. In Hp 1-1 subjects Hp levels dropped after 6-weeks fenofibrate in 94% of subjects, in Hp 2-1 - in 92% and in Hp 2-2 only in 73% of subjects (difference between phenotypes: p=0.002).

Conclusions: Hp levels differ by Hp phenotype in T2D adults. Fenofibrate lowers Hp levels in all phenotypes, however the effect is significantly attenuated in Hp 2-2.