Diabetes as a Determinant of Mortality in Cystic Fibrosis

Abstract

OBJECTIVEDiabetes is increasingly common in cystic fibrosis, but little information describing its influence on mortality exists. Using national U.K. data, in this study we document diabetes-specific mortality rates, estimate the impact of diabetes on survival, and estimate population-attributable fractions.RESEARCH DESIGN AND METHODSThis retrospective cohort study identified 8,029 individuals aged 0–65 years from the U.K. Cystic Fibrosis Registry (1996–2005). A total of 5,892 patients were included in analyses of mortality rates, and 4,234 were included in analyses of risk factors. We calculated age-adjusted mortality rates using Poisson regression, standardized mortality ratios using the population of England and Wales, and relative risks using proportional hazards modeling.RESULTSDuring 17,672 person-years of follow-up, 393 subjects died. The age-adjusted mortality rate was 1.8 per 100 person-years (95% CI 1.6–2.0). The age-adjusted mortality rates per 100 person-years were 2.0 (1.8–2.4) in female subjects and 1.6 (1.4–1.9) in male subjects, and 4.2 (3.4–5.1) in individuals with diabetes vs. 1.5 (1.3–1.7) in those without diabetes. Independent risk factors for death included diabetes (hazard ratio 1.31 [95% CI 1.03–1.67], female sex (1.71 [1.36–2.14]) plus poorer pulmonary function, lower BMI, Burkholderia cepacia infection, absence of Staphylococcus aureus infection, allergic bronchopulmonary aspergillosis, liver disease, prior organ transplantation, and corticosteroid use.CONCLUSIONSIndividuals with cystic fibrosis die earlier if they have diabetes, which, if delayed or better treated, might reasonably extend survival; this hypothesis merits testing.

Screening for cystic fibrosis-related diabetes: a systematic review.

“…Mortality increased with age, but for those with CFRD peaked in the 20-to 29-year age range. 62 The risk of death was higher among females than males, with age-adjusted mortality rates of 2.0 [95% confidence interval (CI) 1.8 to 2.4 age-adjusted mortality rate] and 1.6 (95% CI 1.4 to 1.9 age-adjusted mortality rate), respectively. Those with CFRD had much higher age-adjusted mortality rates at 4.2 (95% CI 3.4 to 5.1 age-adjusted mortality rate) per 100 person-years than those with CF alone: 1.5 (95% CI 1.3 to 1.7 age-adjusted mortality rate per 100 person-years).…”

“…Chamnan et al 62 carried out a retrospective cohort study to determine mortality rates, estimate the risk increase associated with diabetes, and calculate the population attributable fraction (PAF) for mortality associated with diabetes. Their cohort included 8029 people aged 0-65 years, registered on the UK Cystic Fibrosis Registry from 1996 to 2005, of whom 5892 had data for mortality rate follow-up, with 4234 complete data for analysis of risk factors for mortality; 393 subjects died during follow-up.…”

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

“…In addition, CF-related diabetes (CFRD) has negative implications in terms of pulmonary deterioration, observed years before diabetes diagnosis, and mortality (3)(4)(5)(6)(7)(8)(9)(10). CFRD prevalence and health consequences are expected to increase in the future as a result of prolonged survival of CF patients.…”

“…The classic diabetes diagnostic criteria, based on the detection of chronic hyperglycemia (19), were historically aimed at identifying the risk for microvascular complications (9). These are not the primary concern in CFRD.…”

MANAGEMENT OF ENDOCRINE DISEASE: Cystic fibrosis-related diabetes: novel pathogenic insights opening new therapeutic avenues

“…Worryingly, CFRD is associated with significantly increased morbidity and mortality in both children and adults. It has a major detrimental impact on pulmonary function, nutritional status and survival (22,23,24). These deleterious effects of hyperglycemia frequently occur before the diagnosis of overt CFRD is made (25).…”