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

Author:

Januszewski Andrzej S.123ORCID,Young Hayden K.4,Ong Kwok‐Leung1ORCID,Li Liping1,O’Connell Rachel L.1,Lyons Timothy J.56,Kelly Clare57,Zaharieva Dessi P.8,Sullivan David R.1,Scott Russell S.9,Keech Anthony C.1,Jenkins Alicia J.1210,

Affiliation:

1. NHMRC Clinical Trials Centre University of Sydney Sydney New South Wales Australia

2. Department of Medicine University of Melbourne Melbourne Victoria Australia

3. Sydney Pharmacy School University of Sydney Sydney New South Wales Australia

4. Joondalup Health Campus Perth Western Australia Australia

5. Division of Endocrinology, Diabetes, and Metabolic Diseases Medical University of South Carolina Charleston South Carolina USA

6. Diabetes Free South Carolina Blue Cross Blue Shield of South Carolina Columbia South Carolina USA

7. Centre for Public Health Queen's University Belfast Belfast UK

8. Division of Endocrinology, Department of Pediatrics, School of Medicine Stanford University Stanford California USA

9. New Zealand Clinical Research Ltd Christchurch New Zealand

10. Baker Heart and Diabetes Institute Melbourne Victoria Australia

Abstract

ABSTRACTAims/HypothesisIn 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 MethodsIn 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.ResultsThe 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.ConclusionsIn 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.

Funder

National Health and Medical Research Council

Publisher

Wiley

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