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Mannose-binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

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posted on 02.07.2020 by Anne Gedebjerg, Mette Bjerre, Alisa Devedzic Kjaergaard, Rudi Steffensen, Jens Steen Nielsen, Jørgen Rungby, Søren Gunnar Friborg, Ivan Brandslund, Steffen Thiel, Henning Beck-Nielsen, Henrik Toft Sørensen, Troels Krarup Hansen, Reimar Wernich Thomsen
Objective: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease in diabetes, but the nature of the association is unclear. We investigated the association between MBL and risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes.

Research Design and Methods: In a cohort study of 7588 patients with type 2 diabetes, we measured serum MBL in 7305 and performed MBL expression genotyping in 3043. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, and cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses.

Results: Serum MBL and CVE showed a U-shaped association. Compared to the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI, 1.34 to 2.46) for the low-MBL category and 1.48 (95% CI, 1.14 to 1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared to the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI, 0.87 to 2.25) for the low-expression genotype and 1.44 (95% CI, 1.01 to 2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality.

Conclusions: Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for cardiovascular disease in this population.

Funding

The Danish Centre for Strategic Research in Type 2 Diabetes Project (DD2) is supported by the Danish Agency for Science (grant nos. 09-067009 and 09-075724), the Danish Health and Medicines Authority, the Danish Diabetes Association, and an unrestricted donation from Novo Nordisk A/S. Project partners are listed on the www.DD2.nu website. The work of A.G. was supported by the Danish Diabetes Academy, which is funded by an unrestricted grant from the Novo Nordisk Foundation, and by grants from the Danish Heart Foundation (grant nos. 15-R99-A5866-22891) and Aarhus University. In addition, A.G. has received funding from the Danielsen Foundation, Augustinus Foundation, A.P. Møller Foundation, Hertz Foundation, and Bønnelycke Foundation. The Department of Clinical Epidemiology, Aarhus University Hospital, participates in the International Diabetic Neuropathy Consortium research program, which is supported by a Novo Nordisk Foundation Challenge program grant (grant number NNF14SA000 6). The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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