Work

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

Year: 2025

Type: article

Abstract: • Fenofibrate benefit against CVD in type 2 diabetes differ by HP phenotype. • This study investigated whether fenofibrate benefit on sight-threatening diabetic retinopathy (STDR) in type 2 diabetes differ by HP phenotype and levels. • Baseline HP levels and phenotype were not related to STDR risk. • Fenofibrate benefit on STDR was greater in patients with lower baseline HP levels. • STDR benefit of fenofibrate occurred in all HP phenotypes. 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). 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. 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. 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.

Source: Diabetes Research and Clinical Practice

DOI: 10.1016/j.diabres.2025.112080