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.
K. Ong: None. A.S. Januszewski: None. H. Francis: None. A.O. Mangani: None. R.L. O'Connell: None. A. Jenkins: Research Support; Abbott, Viatris Inc. Advisory Panel; Abbott. Research Support; Medtronic. Board Member; Insulin for Life. Research Support; Leona M. and Harry B. Helmsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), Jaeb Center for Health Research, National Institutes of Health, National Health and Medical Research Council Australia. A.C. Keech: Research Support; Abbott, Amgen Inc., Bayer Inc., Kowa Company, Ltd., Mylan. Speaker's Bureau; Novartis Pharmaceuticals Corporation. Research Support; Novartis Pharmaceuticals Corporation, Sanofi, Viatris Inc.
Laboratoires Fournier, Dijon, France and the National Health and Medical Research Council of Australia (NHMRC) (457103, 1024105, 1037786, 1105467)
