title: Diabetes is associated with dramatically decreased survival in female but not male subjects with cystic fibrosis.
abstract: OBJECTIVE
  Survival analysis was performed on a prospectively followed cohort of patients with cystic fibrosis (CF) to determine the impact of the development of diabetes on survival.
  
  
  METHODS
  Clinical data were retrieved for patients diagnosed with CF-related diabetes (CFRD) at the Minnesota CF Center in 1987-2002. Kaplan-Meier survival analysis was performed to estimate median survival. Data were analyzed by Cox regression to evaluate the influence of clinical characteristics at the time of CFRD diagnosis on mortality.
  
  
  RESULTS
  Clinical information was reviewed from 1,081 CF patients. A total of 123 patients with CFRD with fasting hyperglycemia were identified (58 males). Median survival was 49.5 years for male subjects without diabetes, 47.4 years for male subjects with diabetes, 47.0 years for female subjects without diabetes, and 30.7 years for female subjects with diabetes. Only female sex and forced expiratory volume in 1 s at the time of CFRD diagnosis were significant predictors of the subsequent risk of death (P < 0.001). This strong association was not confounded by CFTR genotype, BMI, steroid use, respiratory pathogens, HbA1c, or pregnancy.
  
  
  CONCLUSIONS
  Female subjects with CFRD have a remarkably poorer prognosis compared with all male subjects with CF and female subjects with CF but without diabetes. The etiology of this sex difference is not clear. We speculate it might involve the interaction of female hormones and diabetes on promotion of a proinflammatory state or that androgens might protect male subjects from the catabolic effects of insulin deficiency. Alternatively, the appearance of frank diabetes in female subjects with CF may simply be a marker for some other biological difference that is not immediately apparent.
authors.affiliation: Department of Pediatrics, MMC 742, Minnesota Cystic Fibrosis Center, University of Minnesota, 420 Delaware St. WE, Minneapolis, Minnesota 55455, USA. milla005@umn.edu
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Milla
authors.forename: Joanne
authors.initials: J
authors.lastname: Billings
authors.forename: Antoinette
authors.initials: A
authors.lastname: Moran
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications* / Q000401:mortality* / Q000503:physiopathology; D048909:Diabetes Complications / Q000401:mortality*; D003920:Diabetes Mellitus / Q000401:mortality*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D016019:Survival Analysis; D014797:Vital Capacity