Date of Award

2013

Document type

Thesis

Degree Name

MD (Medical Doctor)

First Supervisor

Professor Alf Nicholson

Second Supervisor

Associate Professor Phil Robinson

Third Supervisor

Associate Professor Sarath Ranganathan

Keywords

Cystic Fibrosis, Glucose Intolerance, Cross-Sectional Studies

Abstract

Cystic Fibrosis (CF) is the most common fatal inherited disease in Caucasians. Mean survival for this condition has increased significantly in recent decades such that extra- pulmonary complications of CF have become more apparent (1). The most important complication is abnormal glucose tolerance (AGT) as it is known to have a negative impact on important CF outcomes such as lung function and nutrition (2). Despite this, AGT in CF remains poorly understood. The overall aim of this thesis was to increase understanding of how AGT affects children and adolescents with CF. This thesis is comprised of 3 studies. The first is a cross sectional study that examined the impact of AGT on a group of children and adolescents attending the CF unit at the Royal Children’s Hospital in Melbourne. This study identified that AGT has a significantly negative impact on children and adolescents with CF including significantly worse lung function, increased admissions and infection with Pseudomonas aeruginosa. This effect was most pronounced in patients with Cystic Fibrosis Related Diabetes (CFRD) but was also present to a lesser extent in those with Impaired Glucose Tolerance (IGT). The second study examined the impact of AGT on structural lung disease in CF. In a retrospective review, spirometry and CT findings were compared in patients with Normal Glucose Tolerance (NGT), IGT and CFRD. Despite stable lung function over 2 years in all 3 groups, CT scores progressed in proportion to worsening glucose tolerance status. Finally, the impact of CF pulmonary exacerbations on glucose tolerance was studied prospectively. An oral glucose tolerance test and continuous glucose monitoring were performed during exacerbations and repeated at follow up. Contrary to a previous study, it was found that glucose tolerance status did not change significantly during exacerbations.

These findings of the first two studies confirm the importance of early diagnosis and treatment of AGT in CF. Structural lung disease progressed more rapidly in patients with AGT despite stable lung function. Glucose tolerance is therefore important as it is strongly associated with progression of lung structural damage. Conventional lung function is not a surrogate for either assessing glucose status or lung structure. Finally, hyperglycaemia found during CF pulmonary exacerbations is unlikely to resolve and consideration should be given to starting those patients on insulin.

Abstract references

1. Reid DW, Blizzard CL, Shugg DM, Flowers C, Cash C, Greville HM.Changes in cystic fibrosis mortality in Australia, 1979-2005. Med J Aust. 2011 Oct 3;195(7):392-5.

2. Moran A, Becker D, Casella SJ, Gottlieb PA, Kirkman MS, Marshall BC, et al. Epidemiology, pathophysiology, and prognostic implications of cystic fibrosis-related diabetes: a technical review. Diabetes Care. 2010 Dec;33(12):2677-83.

File Size

8,255 KB

Comments

A thesis submitted to the Royal College of Surgeons in Ireland for the degree of Doctor of Medicine from the National University of Ireland in 2013.

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