Abstract

Cystic fibrosis-related diabetes affects up to half of cystic fibrosis patients and is associated with increased mortality and more frequent pulmonary exacerbations. However, it is unclear to what degree good glycemic control might mitigate these risks and clinical outcomes have not previously been studied in relation to glucose from the lower airways, the site of infection and CF disease progression. We initially hypothesized that diabetic cystic fibrosis patients with glycosylated hemoglobin (HbA1c) > 6.5% have worse pulmonary function, longer and more frequent exacerbations and also higher sputum glucose levels than patients with HbA1c ≤ 6.5% or cystic fibrosis patients without diabetes. To test this, we analyzed spontaneously expectorated sputum samples from 88 cystic fibrosis patients. The median sputum glucose concentration was 0.70 mM (mean, 4.75 mM; range, 0-64.6 mM). Sputum glucose was not correlated with age, sex, body mass index, diabetes diagnosis, glycemic control, exacerbation frequency or length, or pulmonary function. Surprisingly, sputum glucose was highest in subjects with normal glucose tolerance, suggesting the dynamics of glycemic control, sputum glucose and pulmonary infections are more complex than previously thought. Two-year mean HbA1c was positively correlated with the length of exacerbation admission (p < 0.01), and negatively correlated with measures of pulmonary function (p < 0.01). While total number of hospitalizations for exacerbations were not significantly different, subjects with an HbA1c > 6.5% were hospitalized on average 6 days longer than those with HbA1c ≤ 6.5% (p < 0.01). Current clinical care guidelines for cystic fibrosis-related diabetes target HbA1c ≤ 7% to limit long-term microvascular damage, but more stringent glycemic control (HbA1c ≤ 6.5%) may further reduce the short-term pulmonary complications.

Highlights

  • Proper blood glucose management of cystic fibrosis-related diabetes (CFRD) adds a substantial burden to patients who already spend hours every day managing pulmonary, GI, and other complications of cystic fibrosis (CF)

  • We sought to determine if CFRD worsens health through an increase in sputum glucose (SG), which could foster bacterial growth and worsen pulmonary infections

  • Our study found SG was highest in subjects with normal glucose tolerance (NGT) as compared to IGT or CFRD

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Summary

Introduction

Proper blood glucose management of cystic fibrosis-related diabetes (CFRD) adds a substantial burden to patients who already spend hours every day managing pulmonary, GI, and other complications of cystic fibrosis (CF). In addition to potential long-term complications, evidence suggests that CFRD reduces pulmonary function [3] and increases the frequency and likelihood of treatment failure [4, 5] in pulmonary exacerbations (PEx), the primary cause of mortality in CF [6, 7]. It is unclear by what mechanism CFRD negatively impacts pulmonary health and if stringent glycemic control would reduce these effects. It is frequently hypothesized that CFRD increases sputum glucose (SG), which could support airway pathogens and contribute to PEx [8, 9]

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