Anne Gedebjerg1,2, Mette Bjerre3, Alisa Devedzic Kjaergaard4, Rudi Steffensen5, Jens Steen Nielsen6, Jørgen Rungby7,8, Søren Gunnar Friborg9, Ivan Brandslund10, Steffen Thiel11, Henning Beck-Nielsen6,9, Henrik Toft Sørensen4,12,13, Troels Krarup Hansen14, Reimar Wernich Thomsen4. 1. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark aged@clin.au.dk. 2. Danish Diabetes Academy, Odense University Hospital, Odense, Denmark. 3. Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 4. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Immunology, Aalborg University Hospital, Aalborg, Denmark. 6. DD2, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark. 7. Department of Endocrinology IC, Bispebjerg University Hospital, Copenhagen, Denmark. 8. Copenhagen Center for Translational Research, Bispebjerg University Hospital, Copenhagen, Denmark. 9. Diabetes Research Centre, Department of Endocrinology, Odense University Hospital, Odense, Denmark. 10. Department of Biochemistry, Lillebaelt Hospital, Vejle, Denmark. 11. Department of Biomedicine, Aarhus University, Aarhus, Denmark. 12. Department of Epidemiology, Boston University, Boston, MA. 13. Center for Population Health Sciences, Stanford University, Stanford, CA. 14. Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Abstract
OBJECTIVE: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease (CVD) in diabetes, but the nature of the association is unclear. We investigated the association between MBL and the risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 7,588 patients with type 2 diabetes, we measured serum MBL in 7,305 patients and performed MBL expression genotyping in 3,043 patients. 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, or 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 with the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI 1.34-2.46) for the low-MBL category and 1.48 (95% CI 1.14-1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared with the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI 0.87-2.25) for the low-expression genotype and 1.44 (95% CI 1.01-2.06) 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 CVD in this population.
OBJECTIVE:Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease (CVD) in diabetes, but the nature of the association is unclear. We investigated the association between MBL and the risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 7,588 patients with type 2 diabetes, we measured serum MBL in 7,305 patients and performed MBL expression genotyping in 3,043 patients. 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, or 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 with the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI 1.34-2.46) for the low-MBL category and 1.48 (95% CI 1.14-1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared with the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI 0.87-2.25) for the low-expression genotype and 1.44 (95% CI 1.01-2.06) 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 CVD in this population.
Authors: Michael Hultström; Robert Frithiof; Jonathan Grip; Linnea Lindelöf; Hugo Zeberg; Oskar Eriksson; Olav Rooijackers; Sara Pigazzini; Mari Niemi; Mattia Cordioli; Lindo Nkambule; Tomislav Maricic; Kristina Nilsson Ekdahl; Bo Nilsson; Miklós Lipcsey Journal: Nat Immunol Date: 2022-05-27 Impact factor: 31.250
Authors: Sara Meziani; Giulia Ferrannini; Mette Bjerre; Troels K Hansen; Viveca Ritsinger; Anna Norhammar; Viveca Gyberg; Per Näsman; Lars Rydén; Linda G Mellbin Journal: Cardiovasc Diabetol Date: 2022-07-08 Impact factor: 8.949