Lactoferrin is a novel predictor of fatal ischemic heart disease in diabetes mellitus type 2: Long-term follow-up of the HUNT 1 study

Abstract

Objectives The pathogenesis of diabetes and atherosclerosis is linked through inflammation. Neutrophils contribute to atherosclerotic plaque development, and are dysfunctional in diabetes. The aim of this study was to compare the predictive values of two neutrophil degranulation products, myeloperoxidase and lactoferrin, on long-term risk for fatal ischemic heart disease in persons with newly diagnosed diabetes and controls. Design Prospective population-based cohort study. Setting and patients In 1984–1986, a large population study, HUNT 1, was conducted in Norway. Previously unknown diabetes was diagnosed in 205 persons. A matched control group without diabetes was selected from the HUNT 1. Main outcome measures Fatal ischemic heart disease was registered until 2004. Baseline serum was analysed for myeloperoxidase and lactoferrin. Cox regression analysis with adjustments for age, gender, hypertension, body mass index, established cardiovascular disease and total cholesterol was used to estimate hazard ratios for fatal ischemic heart disease. Results In the diabetes group (200 subjects), the two highest tertiles of lactoferrin predicted fatal ischemic heart disease, hazard ratio 2.54 (95% CI, 1.00–6.45) and 4.06 (1.72–9.60). Myeloperoxidase did not predict death from ischemic heart disease in subjects with diabetes. In the controls (198 subjects), none of the biomarkers predicted fatal ischemic heart disease. Conclusion Increased baseline concentration of lactoferrin strongly predicted the long-term risk for fatal ischemic heart disease in patients with newly diagnosed diabetes. Based on the literature, we hypothesize that the increased concentrations may reflect neutrophil priming caused by hyperglycemia.