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

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

*Corresponding author for this work

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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.

Original languageEnglish
Number of pages6
JournalJournal of Diabetes Investigation
Early online date22 Aug 2024
DOIs
Publication statusEarly online date - 22 Aug 2024

Keywords

  • Haptoglobin
  • Fenofibrate
  • Type 2 diabetes

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