期刊
JOURNAL OF INTERNAL MEDICINE
卷 284, 期 4, 页码 377-387出版社
WILEY
DOI: 10.1111/joim.12783
关键词
diabetes mellitus; furin; mortality; population-based cohort; risk prediction
资金
- Albert Pahlsson Research Foundation
- Crafoord Research Foundation
- Ernhold Lundstrom Research Foundation
- Royal Physiographic Society of Lund
- Ake Wiberg Foundation
- Knut and Alice Wallenberg Foundation
- Goran Gustafsson Foundation
- Swedish Heart- and Lung Foundation
- Swedish Research Council
- Novo Nordisk Foundation
- Skane University Hospital
- European Research Council [649021]
- Swedish Heart and Lung Foundation
- Region Skane
- Swedish Diabetes Foundation
- Novo Nordic Foundation
- Albert Pahlsson Foundation
- Linneus Foundation for the Lund University Diabetes Center
- Swedish Foundation for Strategic Research [IRC15-0067]
- Academy of Finland [266661]
- Sigrid Juselius Foundation
- Finnish Foundation of Cardiovascular Research
- European Research Council (ERC) [649021] Funding Source: European Research Council (ERC)
Background. Diabetes mellitus is linked to premature mortality of virtually all causes. Furin is a proprotein convertase broadly involved in the maintenance of cellular homeostasis; however, little is known about its role in the development of diabetes mellitus and risk of premature mortality. Objectives. To test if fasting plasma concentration of furin is associated with the development of diabetes mellitus and mortality. Methods. Overnight fasted plasma furin levels were measured at baseline examination in 4678 individuals from the population-based prospective Malmo Diet and Cancer Study. We studied the relation of plasma furin levels with metabolic and hemodynamic traits. We used multivariable Cox proportional hazards models to investigate the association between baseline plasma furin levels and incidence of diabetes mellitus and mortality during 21.3-21.7 years follow-up. Results. An association was observed between quartiles of furin concentration at baseline and body mass index, blood pressure and plasma concentration of glucose, insulin, LDL and HDL cholesterol (vertical bar 0.11 vertical bar <= beta <= vertical bar 0.31 vertical bar, P<0.001). Plasma furin (hazard ratio [HR] per one standard deviation increment of furin) was predictive of future diabetes mellitus (727 events; HR=1.24, CI=1.14-1.36, P<0.001) after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive treatment, alcohol intake and fasting plasma level of glucose, insulin and lipoproteins cholesterol. Furin was also independently related to the risk of all-cause mortality (1229 events; HR=1.12, CI=1.05-1.19, P=0.001) after full multivariable adjustment. Conclusion. Individuals with high plasma furin concentration have a pronounced dysmetabolic phenotype and elevated risk of diabetes mellitus and premature mortality.
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