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Randomized Controlled Trial
. 2025 Apr:222:112080.
doi: 10.1016/j.diabres.2025.112080. Epub 2025 Mar 11.

Relationship of haptoglobin phenotype and levels with sight-threatening diabetic retinopathy in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in diabetes (FIELD) substudy

Kwok Leung Ong  1 , Andrzej S Januszewski  2 , Habib Francis  1 , Rachel L O'Connell  1 , Abubakar Mangani  2 , Liping Li  1 , Peter G Colman  3 , David R Sullivan  4 , Russell S Scott  5 , Alicia J Jenkins  6 , Anthony C Keech  7 ; FIELD Study Investigators
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Free article
Randomized Controlled Trial

Relationship of haptoglobin phenotype and levels with sight-threatening diabetic retinopathy in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in diabetes (FIELD) substudy

Kwok Leung Ong et al. Diabetes Res Clin Pract. 2025 Apr.
Free article

Abstract

Aims: Haptoglobin (HP) phenotype has been reported to modulate fenofibrate benefit on coronary artery disease in type 2 diabetes. It is unknown whether HP phenotype and levels modulate fenofibrate benefit on sight-threatening diabetic retinopathy (STDR).

Methods: In plasma from 8,047 Australasian adults with type 2 diabetes in the FIELD trial, HP phenotype was determined, and HP levels were measured at baseline and after six-week fenofibrate run-in.

Results: There were 307 new first on-trial STDR events over five years. Baseline HP levels and phenotype were not related to STDR risk. Fenofibrate benefit on STDR vs. placebo (-32 % overall), was greatest in participants with the lowest baseline HP level tertile (hazard ratio [95 % CI] 0.41 [0.26-0.65], vs. 0.82 [0.56-1.21] and 0.84 [0.56-1.27] for tertiles 2 and 3 respectively, P for heterogeneity = 0.019). During run-in, fenofibrate reduced HP levels by 20.7 %. However, fenofibrate benefit on STDR did not differ significantly by HP phenotype or change in HP levels during run-in after adjustment for confounding factors.

Conclusions: Regarding STDR, fenofibrate benefit is greatest in type 2 diabetes patients with the lowest baseline HP levels, which may reflect patients more susceptible to oxidative retinal injury. All HP phenotypes benefit from fenofibrate.

Keywords: Biomarkers; Fenofibrate; Haptoglobin; Retinopathy; Type 2 diabetes.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Fournier Pharma (now part of Abbott Pharmaceuticals) sponsored the FIELD trial but had no role in data collection, analysis, or interpretation. D.R.S. has received grants or contracts from Amgen, Arrowhead, Ionis, Novartis and Regeneron, Alirocumab samples from Sanofi, and consulting fees and honoraria from Amgen and Novartis. D.R.S. has participated as a member of the Data Safety Monitoring Board or Advisory board of the LIPID, FIELD and Nomad studies, and clinical committee chairman of the Australian Atherosclerosis Society Executive. A.J.J. has received honoraria from CSL and GSK, and travel support for conference attendance from American Diabetes Association and CSL. A.J.J. has served as an advisory panel member for Abbott, CSL and GSK, and has received research support from Abbott, Abbvie and Viatris, and grant funding from the NHMRC to support research activities, including relating to the FIELD trial. A.J.J. has also served as a honorary board member of an international diabetes aid Insulin For Life (a non-governmental organization), member of the International Diabetes Federation Disaster Committee, and Chair-Elect of the International Diabetes Federation Western Pacific Region. A.C.K. has received program grant and Senior Research Fellowship from the NHMRC to support all research activities. A.C.K. has received research support from Abbott, Amgen, Bayer, Mylan, Novartis and Sanofi, honoraria from Novartis, and drugs for research trials from Viatris and Aspen. A.C.K. has participated as a member of the Data Safety Monitoring Board of the PROMINENT trial (Kowa). All other authors declare no conflict of interest].

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