Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

TY - JOUR

T1 - Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes

T2 - A 12-Year Follow-up Study

AU - Østergaard, Jakob A

AU - Thiel, Steffen

AU - Lajer, Maria

AU - Steffensen, Rudi

AU - Parving, Hans-Henrik

AU - Flyvbjerg, Allan

AU - Rossing, Peter

AU - Tarnow, Lise

AU - Hansen, Troels K

N1 - © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2015/10

Y1 - 2015/10

N2 - OBJECTIVE: Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this.RESEARCH DESIGN AND METHODS: We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 years [95% CI 40-42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m(2) [95% CI 63-70]) and 174 normoalbuminuric patients (103 men, age 43 years [95% CI 41-44], eGFR 93 mL/min/1.73 m(2) [95% CI 91-95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL concentration was estimated by comparing patients with MBL concentrations above or below the median.RESULTS: Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002).CONCLUSIONS: High MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.

AB - OBJECTIVE: Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this.RESEARCH DESIGN AND METHODS: We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 years [95% CI 40-42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m(2) [95% CI 63-70]) and 174 normoalbuminuric patients (103 men, age 43 years [95% CI 41-44], eGFR 93 mL/min/1.73 m(2) [95% CI 91-95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL concentration was estimated by comparing patients with MBL concentrations above or below the median.RESULTS: Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002).CONCLUSIONS: High MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.

U2 - 10.2337/dc15-0851

DO - 10.2337/dc15-0851

M3 - Journal article

C2 - 26180106

SN - 0149-5992

VL - 38

SP - 1898

EP - 1903

JO - Diabetes Care

JF - Diabetes Care

IS - 10

ER -