Association of Urine Haptoglobin With Risk of All-Cause and Cause-Specific Mortality in Individuals With Type 2 Diabetes: A Transethnic Collaborative Work

Abstract

OBJECTIVE: Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality. RESULTS: A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5-12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3-10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02-2.11], 2.28 [1.62-3.21], and 4.64 [3.39-6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15-2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09-3.42] and adjusted HR 1.49 [1.14-1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor. CONCLUSIONS: Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.