Affiliation:
1. Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
2. Diabetes Centre, Admiralty Medical Centre, Singapore
3. National Healthcare Group Polyclinic, Singapore
4. Saw Swee Hock School of Public Health, National University of Singapore, Singapore
Abstract
Abstract
Background
Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein in the transforming growth factor-beta superfamily. We sought to study whether LRG1 might predict risk for all-cause and cause-specific mortality in individuals with type 2 diabetes.
Methods
2012 outpatients with type 2 diabetes were followed for a median of 7.2 years and 188 death events were identified. Association of LRG1 with risk for mortality was assessed by multivariable Cox regression models.
Results
Participants with a higher concentration of LRG1 had an increased risk for all-cause mortality [HR (95% CI), 1.76 (1.03–3.01), 1.75 (1.03–2.98), and 4.37 (2.72–7.02) for quartiles 2, 3, and 4, respectively, compared to quartile 1]. The association remained significant after adjustment for known cardio-renal risk factors including estimated glomerular filtration rate and albuminuria [adjusted HR 2.76 (1.66–4.59), quartile 4 versus 1]. As a continuous variable, a 1-SD increment in LRG1 was associated with 1.34 (1.14–1.57)-fold adjusted risk for all-cause mortality. High plasma LRG1 was independently associated with mortality attributable to cardiovascular disease, infection, and renal diseases. Adding LRG1 into a clinical variable-based model improved discrimination (c statistics from 0.828 to 0.842, P = 0.006) and reclassification (net reclassification improvement 0.47, 95% CI 0.28–0.67) for prediction of 5-year all-cause mortality.
Conclusion
Plasma LRG1 predicts risk for all-cause mortality and mortality attributable to cardiovascular disease, infection, and renal disease independent of known cardio-renal risk factors. It may be a potential novel biomarker to improve risk stratification in individuals with type 2 diabetes.
Funder
Khoo Teck Puat Hospital STAR Grant 18203
Singapore National Medical Research Council Grants
Publisher
Oxford University Press (OUP)
Subject
Biochemistry (medical),Clinical Biochemistry
Cited by
4 articles.
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