Abstract

Objective: Longer survival of patients with cystic fibrosis has increased the occurrence of cystic fibrosis-related diabetes (CFRD). This study documents the incidence of CFRD and evaluates the association between mutations responsible for CF and incident CFRD, while identifying potential risk factors.

Research Design and Methods: Population-based longitudinal study of 50 CF speciality clinics in the United Kingdom. Subjects included 8,029 individuals aged 0 – 64 years enrolled on the UK CF Registry during 1996 – 2005. 5,196 with data and without diabetes were included in analyses of incidence, and 3,275 with complete data in analyses of risk factors. Diabetes mellitus was defined by physician diagnosis, oral glucose tolerance testing, or treatment with hypoglycemic drugs.

Results: 526 individuals developed CFRD over 15,010 person-years. The annual incidence was 3.5%. The incidence was higher in females and in patients with mutations in CF transmembrane conductance regulator (CFTR) gene in classes I and II. In a multivariate model of 377 cases of 3,275 patients, CFTR class (RR 1.70, 1.16 - 2.49, class I or II vs. others), increasing age, female sex, worse pulmonary function, liver dysfunction, pancreatic insufficiency, and corticosteroid use were independently associated with incident diabetes.

Conclusions: The incidence of CFRD is high in Britain. CFTR class I and II mutations increase the risk of diabetes independent of other risk factors including pancreatic exocrine dysfunction.