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

Am J Respir Crit Care Med. 2015 Jan 15;191(2):194-200. doi: 10.1164/rccm.201403-0576OC.

Abstract

Rationale: 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.

Objectives: 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.

Methods: Chart review was performed on 664 patients followed from 2008 to 2012.

Measurements and main results: 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.

Conclusions: Despite substantial improvement over time, mortality for CFRD patients greater than 30 years remains higher than for patients with CF without diabetes.

Keywords: cystic fibrosis–related diabetes; prognosis; sex differences; survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / mortality*
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / mortality*
  • Disease Progression
  • Female
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prevalence
  • Risk Factors
  • Sex Distribution
  • Young Adult