TY - JOUR
T1 - Mannose-binding lectin and risk of infections in type 2 diabetes
T2 - A Danish cohort study
AU - Gedebjerg, Anne
AU - Thomsen, Reimar Wernich
AU - Kjaergaard, Alisa Devedzic
AU - Steffensen, Rudi
AU - Nielsen, Jens Steen
AU - Rungby, Jørgen
AU - Friborg, Søren Gunnar
AU - Brandslund, Ivan
AU - Thiel, Steffen
AU - Beck-Nielsen, Henning
AU - Sørensen, Henrik Toft
AU - Hansen, Troels Krarup
AU - Bjerre, Mette
N1 - Funding Information:
This work was supported by The Danish Centre for Strategic Research in Type 2 Diabetes Project (DD2) which 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 Aase and Ejnar 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 sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Funding Information:
We are grateful to all participants in the DD2 study. We thank Hanne Petersen and Karen Mathiassen for their assistance with the large-volume measurements of serum MBL and hs-CRP. We gratefully acknowledge Sia Kromann Nicolaisen for assistance with data management. This work was supported by The Danish Centre for Strategic Research in Type 2 Diabetes Project (DD2) which 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 Aase and Ejnar Danielsen Foundation, Augustinus Foundation, A.P. M?ller Foundation, Hertz Foundation, and B?nnelycke 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 sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report. This study was presented as a poster presentation at the annual virtual meeting of the European Association for the Study of Diabetes (EASD), 21-25 September, 2020. All authors have seen and approved the content, have contributed significantly to the work, and fulfill the criteria given in the Authorship paragraph. The article is the authors' original work. The authors did not receive any writing assistance or copy editing outside the author group. The manuscript has not been submitted or accepted for publication elsewhere.
Publisher Copyright:
© 2021 Elsevier Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Aims: In individuals at increased risk of infections, e.g., patients with type 2 diabetes, low MBL may have detrimental effects. We used the Mendelian randomization principle to examine whether genetically low MBL is a risk factor for developing infections in patients with type 2 diabetes. Methods: Serum MBL (n = 7305) and MBL genotype (n = 3043) were determined in a nationwide cohort of patients with new type 2 diabetes and up to 8 years follow-up for hospital-treated infections and community-based antimicrobial prescriptions. The associations were examined in spline and Cox regression analyses. Results: 1140 patients (16%) were hospitalized with an infection and 5077 patients (70%) redeemed an antimicrobial prescription. For low (≤100 μg/L) versus intermediate (101–1000 μg/L) serum MBL concentration, the adjusted hazard ratios (aHRs) were 1.13(95% confidence interval, 0.96–1.33) for any hospital-treated infections and 1.19(1.01–1.41) for bacterial infections. Low MBL expression genotype was not associated with risk of any hospital-treated infections except for diarrheal diseases (aHR 2.23[1.04–4.80]). Low MBL expression genotype, but not low serum MBL, was associated with increased risk for antimicrobial prescriptions (aHR 1.18[1.04–2.34] and antibacterial prescriptions 1.20[1.05–1.36]). Conclusions: Low MBL is a weak causal risk factor for developing infections in patients with type 2 diabetes.
AB - Aims: In individuals at increased risk of infections, e.g., patients with type 2 diabetes, low MBL may have detrimental effects. We used the Mendelian randomization principle to examine whether genetically low MBL is a risk factor for developing infections in patients with type 2 diabetes. Methods: Serum MBL (n = 7305) and MBL genotype (n = 3043) were determined in a nationwide cohort of patients with new type 2 diabetes and up to 8 years follow-up for hospital-treated infections and community-based antimicrobial prescriptions. The associations were examined in spline and Cox regression analyses. Results: 1140 patients (16%) were hospitalized with an infection and 5077 patients (70%) redeemed an antimicrobial prescription. For low (≤100 μg/L) versus intermediate (101–1000 μg/L) serum MBL concentration, the adjusted hazard ratios (aHRs) were 1.13(95% confidence interval, 0.96–1.33) for any hospital-treated infections and 1.19(1.01–1.41) for bacterial infections. Low MBL expression genotype was not associated with risk of any hospital-treated infections except for diarrheal diseases (aHR 2.23[1.04–4.80]). Low MBL expression genotype, but not low serum MBL, was associated with increased risk for antimicrobial prescriptions (aHR 1.18[1.04–2.34] and antibacterial prescriptions 1.20[1.05–1.36]). Conclusions: Low MBL is a weak causal risk factor for developing infections in patients with type 2 diabetes.
KW - Association
KW - Cohort study
KW - Epidemiology
KW - Infection
KW - Mannose-binding lectin
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85101138809&partnerID=8YFLogxK
U2 - 10.1016/j.jdiacomp.2021.107873
DO - 10.1016/j.jdiacomp.2021.107873
M3 - Journal article
AN - SCOPUS:85101138809
SN - 1056-8727
VL - 35
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
IS - 5
M1 - 107873
ER -