Early glucose abnormalities are associated with pulmonary inflammation in young children with cystic fibrosis

Bernadette J Prentice; Chee Y Ooi; Roxanne E Strachan; Shihab Hameed; Saeideh Ebrahimkhani; Shafagh A Waters; Charles F Verge; John Widger

doi:10.1016/j.jcf.2019.03.010

Early glucose abnormalities are associated with pulmonary inflammation in young children with cystic fibrosis

J Cyst Fibros. 2019 Nov;18(6):869-873. doi: 10.1016/j.jcf.2019.03.010. Epub 2019 Apr 26.

Authors

Bernadette J Prentice¹, Chee Y Ooi², Roxanne E Strachan³, Shihab Hameed⁴, Saeideh Ebrahimkhani⁵, Shafagh A Waters³, Charles F Verge⁴, John Widger⁶

Affiliations

¹ Department of Respiratory Medicine, Sydney Children's Hospital, Randwick, NSW, Australia; School of Women's and Children's Health, Medicine, The University of New South Wales, Randwick, NSW, Australia; Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC), Sydney, Australia. Electronic address: bernadette.prentice@health.nsw.gov.au.
² School of Women's and Children's Health, Medicine, The University of New South Wales, Randwick, NSW, Australia; Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC), Sydney, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.
³ School of Women's and Children's Health, Medicine, The University of New South Wales, Randwick, NSW, Australia; Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC), Sydney, Australia.
⁴ School of Women's and Children's Health, Medicine, The University of New South Wales, Randwick, NSW, Australia; Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC), Sydney, Australia; Department of Endocrinology, Sydney Children's Hospital, Randwick, NSW, Australia.
⁵ School of Women's and Children's Health, Medicine, The University of New South Wales, Randwick, NSW, Australia.
⁶ Department of Respiratory Medicine, Sydney Children's Hospital, Randwick, NSW, Australia; School of Women's and Children's Health, Medicine, The University of New South Wales, Randwick, NSW, Australia; Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC), Sydney, Australia.

PMID: 31036487
DOI: 10.1016/j.jcf.2019.03.010

Abstract

Background: Children with CF are insulin deficient from infancy but very little is known about the impact of glucose abnormalities in early life. We aimed to identify and describe interstitial glucose levels in CF children <6 years and to evaluate the association with pulmonary infection and inflammation.

Methods: We assessed 18 children (5 females) with median age of 3.2 years (range 0·9-5.5) with Continuous Glucose Monitoring for 3 days. Bronchoalveolar lavage (BAL) fluid was cultured for known pathogenic microbial agents and assessed for total white blood cells, percentage of neutrophils and IL-8 level.

Results: Peak sensor glucose (SG) was >11.1 mmol/L in 39% of participants. The percentage neutrophil count on BAL was positively correlated with elevated SG (peak SG r_s = 0.48, p = .044) and with glucose variability (SG standard deviation r = 0.62, β = 38.5, p = .006). BAL IL-8 level was significantly correlated with all measures of CGM hyperglycemia including % time > 7.8 mmol/L (p = .008) and standard deviation (p < .001). Participants with a history of Pseudomonas aeruginosa had a higher % time > 7.8 mmol/L glucose (16% versus 3%, p = .015).

Conclusion: Children with CF frequently demonstrate elevated SG levels before age 6 years, which are associated with increased pulmonary inflammation and Pseudomonas aeruginosa infection. Transient SG elevations into the diabetic range (≥11.1 mmol/L) were identified in children from 1 year of age.

Keywords: CGM; Continuous glucose monitoring; Cystic fibrosis; Cystic fibrosis-related diabetes; Inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Australia / epidemiology
Blood Glucose / analysis
Bronchoalveolar Lavage Fluid* / immunology
Bronchoalveolar Lavage Fluid* / microbiology
Child, Preschool
Correlation of Data
Cystic Fibrosis* / blood
Cystic Fibrosis* / diagnosis
Cystic Fibrosis* / epidemiology
Cystic Fibrosis* / microbiology
Female
Humans
Hyperglycemia* / diagnosis
Hyperglycemia* / immunology
Infant
Interleukin-8 / analysis
Leukocyte Count / methods
Male
Monitoring, Physiologic / methods
Monitoring, Physiologic / statistics & numerical data
Neutrophils*
Pneumonia* / blood
Pneumonia* / diagnosis
Pseudomonas Infections* / blood
Pseudomonas Infections* / diagnosis
Pseudomonas aeruginosa / isolation & purification*

Substances

Blood Glucose
Interleukin-8