Journal Article

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

Ong, Kwok‐Leung, Zaharieva, Dessi P., Scott, Russell S., Li, Liping, Kelly, Clare, Januszewski, Andrzej S., O’Connell, Rachel L., Young, Hayden K., Lyons, Timothy J., Keech, Anthony C., Sullivan, David R., Jenkins, Alicia J.

2024

Overview

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. Haptoglobin (Hp) levels differed by Hp phenotype in adults with type 2 diabetes. Fenofibrate decreased Hp levels in all Hp phenotypes. A higher baseline Hp level and a smaller fenofibrate‐related decrease in Hp levels in Hp 2‐2 phenotype subjects might be indicative of a lower protective efficacy.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Aged / Angioplasty / Biomarkers / Cardiovascular disease / Coronary vessels / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - drug therapy / Female / Fenofibrate / Fenofibrate - therapeutic use / Genotype & phenotype / Haptoglobin / Haptoglobins / Hemoglobin / High density lipoprotein / Humans / Hypolipidemic Agents - therapeutic use / Male / Middle Aged / Original / Phenotype / Phenotypes / Placebos / Plasma / Type 2 diabetes / Vein & artery diseases / Vitamin E / White people