321-OR: Haptoglobin (Hp) Levels and Phenotype Are Unrelated to Severe Retinopathy in Type 2 Diabetes, but Lower Hp Reductions by Fenofibrate Are Associated with Greater Retinopathy Benefit—A FIELD Trial Study

• Published in: Diabetes (New York, N.Y.) Vol. 73; no. Supplement_1; p. 1
• Main Authors: LEUNG ONG, KWOK, JANUSZEWSKI, ANDRZEJ S., FRANCIS, HABIB, MANGANI, ABUBAKAR SIDDIQ O., O'CONNELL, RACHEL L., JENKINS, ALICIA, KEECH, ANTHONY C.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 14.06.2024
• Subjects: Coronary artery; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetic retinopathy; Fenofibrate; Genotype & phenotype; Genotypes; Haptoglobin; Kidney diseases; Oxidants; Phenotypes; Retinopathy
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db24-321-OR

Background: The abundant plasma protein Hp has anti-oxidant and anti-inflammatory effects. Its genotype/phenotype modulates chronic diabetes complication risk and fenofibrate benefit on coronary artery and kidney disease in type 2 diabetes (T2D). It is unknown whether Hp phenotype and level are associated with risk of sight-threatening diabetic retinopathy (STDR) and fenofibrate benefit. Fenofibrate reduced STDR risk by 31% in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Methods: Hp phenotype and level were measured in 8047 FIELD subjects at baseline and randomization (after a 16-week run-in with fenofibrate in the last 6-weeks). Results: There were 307 on-trial STDR events over 5 years. Hp phenotype and baseline levels were not related to STDR risk. Fenofibrate benefit on STDR risk appeared greater for the Hp 2-1/2-2 phenotypes, but p for heterogeneity was >0.05 (Table 1). During run-in fenofibrate reduced Hp level by 20.7%, p<0.001. Fenofibrate benefit was greatest in those with the lowest tertile of baseline Hp levels as well as among those in whom Hp levels decreased least with treatment. Conclusion: Whilst baseline Hp levels and phenotype are not strongly related to STDR risk in T2D Hp levels and phenotype identify subjects more likely to benefit from fenofibrate.