ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes
Research output: Contribution to journal › Journal article › Research › peer-review
AIMS: Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all-cause mortality in three single-institution outpatient cohorts.
METHODS: Genotype-based analyses were performed in 269 patients from Hillerød Hospital (HIH) (follow-up: 12 years) and in 439 patients with diabetic nephropathy and 437 patients with persistent normoalbuminuria from the Steno Diabetes Center (SDC) (follow-up: 9.5 years). Patients not on renin-angiotensin system (RAS)-blocking treatment were included in analyses of serum ACE activity (HIH: n = 208) and plasma ACE concentration (SDC: n=269).
RESULTS: In the HIH cohort, carrying a D-allele was associated with excess mortality (hazard ratio (HR) = 4.0 (95% confidence interval (CI) 1.0-16)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.0-1.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not.
CONCLUSION: In unselected patients with type 1 diabetes, carrying the ACE D-allele and high spontaneous serum ACE activity were associated with 12-year excess mortality. These findings could not be reproduced in two other cohorts with persistent normoalbuminuria or diabetic nephropathy.
Original language | English |
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Journal | Journal of the Renin-Angiotensin-Aldosterone System |
Volume | 16 |
Issue number | 2 |
Pages (from-to) | 374-81 |
Number of pages | 8 |
ISSN | 1470-3203 |
DOIs | |
Publication status | Published - Jun 2015 |
- Adult, Cohort Studies, Diabetes Mellitus, Type 1, Female, Genetic Predisposition to Disease, Humans, INDEL Mutation, Male, Peptidyl-Dipeptidase A, Phenotype, Proportional Hazards Models, Renin-Angiotensin System
Research areas
ID: 161846154