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Title: Complications in cystic fibrosis-related diabetes
Author: Choudhury, Maitrayee
ISNI:       0000 0004 6349 4159
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2017
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Cystic fibrosis-related diabetes (CFRD) is a secondary form of diabetes, associated with increasing age in subjects with Cystic Fibrosis (CF). With improved life expectancy, CFRD is anticipated to increase in prevalence in addition to its complications. The aim of this study was to investigate the use of HbA1c as an early predictor of disease, as well as investigate microvascular and macrovascular complications in an adult CF cohort attending the All Wales Cystic Fibrosis Centre. The current method of using the conventional oral glucose tolerance test (OGTT) to diagnose CFRD was compared to using glycated haemoglobin (HbA1c). The findings demonstrated that a HbA1c value ≥ 5.5%/36mmol/mol was significantly predictive of the development of dysglycaemia over a 6-year period. The association between HbA1c and development of diabetic retinopathy (DR) was analysed. The study demonstrated 23% of CF patients with CFRD screened for DR had evidence of moderate to severe diabetic retinopathy. They had a higher HbAc1 and longer duration of CFRD compared to those without severe forms of DR. This suggests that microvascular complications are present in CFRD and to a similar extent as in type 1 diabetes mellitus. The prevalence of cardiac autonomic neuropathy (CAN) in CFRD was tested in 71 subjects with CF. CF subjects who were of an older age group demonstrated an inverse correlation with heart rate variability (HRV) during deep breathing (p < 0.05). CF dysglyaemic individuals with severe forms of diabetic retinopathy had reduced HRV during deep breathing compared to subjects with mild or no DR (p < 0.05). The presence of arterial stiffness in CFRD was examined in 65 CF subjects and 31 healthy volunteers. Age, gender and mean arterial pressure were significant predictors of increased augmentation index (AIx) and pulse wave velocity (PWV). Glycaemic control did not influence the arterial stiffness measurement outcomes. The CF group demonstrated a greater Aix than healthy volunteers (HV) (P < 0.05) when other variables were controlled in the analysis, suggesting possible increased inflammatory mechanism leading to increased Aix accounting for these findings. CF dysglycaemic subjects had greater PWV than CFNGT subjects which was only significant at the 10% level. The study findings demonstrate HbA1c has a predictive value in the diagnosis of CFRD based on a positive OGTT. Severe DR is prevalent in CFRD and is associated with a reduction in HRV during deep breathing. Glycaemic control is not predictive of arterial stiffness, in contrast to age, gender and MAP. Thus future consideration of the use of HbA1c may help to predict individuals with underlying dysglycaemia and reduce the risk of the development of associated microvascular complications.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General)