Diabetes-related mortality in adults with cystic fibrosis. Role of genotype and sex

Diabetes is associated with increased mortality in cystic fibrosis. Aggressive screening and early institution of insulin treatment significantly reduced this risk over the period of 1992-2008. To determine if progressive improvement in cystic fibrosis-related diabetes (CFRD) mortality has continued since 2008, and examine associations with CFTR genotypes linked to pancreatic insufficiency and to sex. Chart review was performed on 664 patients followed from 2008 to 2012. Overall mortality for patients with CFRD was 1.8 per 100 person-years, compared with 0.5 in patients with CF without diabetes (P = 0.0002); neither rate changed significantly from mortality reported for 2003-2008. Genotype impacted both mortality and diabetes risk: adults with severe CFTR genotypes experienced greater mortality at every age older than 32 years than those with mild genotypes (P = 0.002), and the risk of developing CFRD was also greatly increased in those with severe genotypes (prevalence 60% in adult patients with severe vs. 14% in adults with mild mutations). CFRD had a direct influence on mortality because it was associated with increased risk of death within each genotype category (20 vs. 2%, P = 0.007 for mild; 12 vs. 4%, P = 0.012 for severe). There was also a sex difference in adults with severe CFTR genotypes; both mortality and CFRD prevalence were higher at every age in females than males. Despite substantial improvement over time, mortality for CFRD patients greater than 30 years remains higher than for patients with CF without diabetes.