Lewis, Nina Ruth
Morbidity associated with coeliac disease.
PhD thesis, University of Nottingham.
Historically considered a rare disorder, it is now appreciated that coeliac disease is a major health problem affecting 1% of the population. The ability to screen for coeliac disease non-invasively and on a large-scale with the development of highly sensitive and specific serological tests has helped crystallise the coeliac iceberg of contemporary disease. Clinically overt coeliac disease only makes up the tip of this iceberg and accounts for only the minority of cases of coeliac disease. The majority of coeliacs in comparison have few obvious symptoms despite the presence of the enteropathy, have atypical symptoms or have physiological derangements such as iron deficiency anaemia.
Recent population-based studies have provided more robust estimates of risks traditionally associated with clinically overt coeliac disease such as mortality, malignancy and fracture. However other morbidity and perhaps potential benefits associated with the spectrum that is contemporary coeliac disease and the effect of treatment need clarification. The benefits and possible harm of detection and treatment of coeliac disease in otherwise asymptomatic, healthy people or those presenting with non-classic features or mild enteropathy disease is also not clear.
The rate of diagnosis of coeliac disease in developed countries has increased dramatically since the introduction of serological tests without an obvious environmental precipitant.
The principal aspect of this thesis is to examine the vascular, hepatic and psychosocial profile in people with contemporary coeliac disease to clarify the morbidity and perhaps potential benefits associated with contemporary coeliac disease. The physiological derangements and morbidity of mild versus severe enteropathy celiac disease; and coeliacs presenting with classic disease, silent disease or gastrointestinal symptoms will be compared. The benefits and possible harm of detecting contemporary coeliac disease will also be explored by examining the effect of treatment with a gluten-free diet. Reported possession of conventional breast cancer risk factors by female coeliacs will be examined and compared to those possessed by the general population to further explore potential explanations for the apparent 50% reduced risk of breast cancer in women with coeliac disease. The socio-economic distribution of people with incident coeliac disease will also be examined to improve our understanding of the aetiology of the disorder in a further part to the thesis.
1. To describe the relationship between degree of enteropathy and physiological derangement, clinical features in incident coeliac disease
2. To examine the incidence of clinically diagnosed coeliac disease by socioeconomic status
3. To quantify the impact of diagnosed coeliac disease on the risk of
4. To estimate the vascular risk profile at diagnosis of coeliac disease and quantify any change following treatment with a gluten-free diet
5. To estimate the quality of life at diagnosis of coeliac disease and observe any change following exposure to a gluten-free diet
6. To describe the breast cancer risk profile in women with coeliac disease and compare to that of the general population
To examine objectives 1,2 and 3 I generated a historical cohort of people who had been diagnosed with coeliac disease at Nottingham and Sheffield. Dietetic, histopathology, immunology, clinical coding and outpatient records were used to retrospectively identify incident cases of coeliac disease at Nottingham University Hospital and Royal Hallamshire Hospital, Sheffield. I identified 1008 adults with incident coeliac disease between 1st January 2000 and 31st December 2006 at these centres that made up this historical cohort. Demographic, clinical, histological and laboratory data were collected on these identified incident cases of coeliac disease through systematic collection.
Using a longitudinal, observational cohort study design, objectives 3 and 4 were examined. Consecutive cases of incident coeliac disease were identified at Derby, Nottingham, Sheffield study centres using clinical alerts and records; dietetic alerts and records; histopathology and immunology databases. Extensive efforts were made to identify all incident adults with coeliac disease at these three centres to help generate an unselected, large and contemporary cohort. Data was systematically collected on the vascular risk profile and health-related quality of life in adults newly diagnosed with coeliac disease and any change following treatment with a gluten-free diet determined.
Objective 5 was studied in a cross-sectional, questionnaire-based survey where the reported possession of conventional breast cancer risk factors by female coeliacs were systematically collected and compared to those possessed by the general population. Female coeliacs that were members of Coeliac UK (population-based cohort) and identified female coeliacs that have attended between 1st January 2000 – 31st December 2006 Nottingham University Hospital, Nottingham; Royal Hallamshire Hospital, Sheffield; or Derby Hospitals NHS Foundation Trust for management of their coeliac disease (historical hospital-based cohort) formed the study population. Female coeliacs with either incident or prevalent coeliac disease were identified using clinical alerts and records; dietetic alerts and records; histopathology and immunology databases. Coeliac UK, the principal national society for people with coeliac disease, has over 70,000 registered members from which we selected a random sample of 9000 women from those women identified as being over the age of 35 years who on their membership information had registered a current UK postal address and they had reported that they have coeliac disease.
Coeliacs with mild enteropathy have few biochemical deficiencies at diagnosis of coeliac disease and therefore show no important biochemical improvements following treatment with a gluten-free diet in comparison to those with severe enteropathy coeliac disease. Approximately one-third of coeliacs with mild enteropathy celiac disease had negative EMA serology at diagnosis and had significantly lower tTG values in comparison to those with severe enteropathy coeliac disease. Diarrhoea was the most common symptom reported in adults being diagnosed with mild enteropathy coeliac disease and more common than that observed in severe enteropathy. Iron deficiency anaemia was much less common in mild enteropathy compared to severe enteropathy.
There was a strong, independent graded association between the incidence rate of new diagnoses of coeliac disease and socio-economic status with the rate twice as high in adults from affluent areas compared with that in adults living in poorer areas. Socioeconomic status was not associated with features of more severe coeliac disease.
Hypertransaminasaemia was uncommon (<2%) in newly diagnosed adults with coeliac disease and in those patients with an abnormal test 86% normalised following a year of treatment with a gluten-free diet. The presence of elevated transaminases in incident coeliac disease was associated independently with clinical features of malabsorption and more severe histological features of intestinal inflammation on duodenal biopsy.
At diagnosis coeliacs have much lower total cholesterol levels than the general population with the observed reduction greater in men (21%) than in women (9%) with no increase in total cholesterol observed on treatment with a gluten-free diet. Furthermore, HDL cholesterol showed a small but statistically significant increase following treatment.
The observed vascular risk profile in our study suggests both protective and adverse associations of coeliac disease. The lower mean levels of total cholesterol, LDL cholesterol, fibrinogen; the higher likelihood of being from more affluent social class; and the small but significant rise in HDL cholesterol and reduction in blood pressure amongst coeliacs presenting with gastrointestinal symptoms observed following treatment with a gluten-free diet suggests coeliacs have favourable vascular risk profile features in comparison to the general population. However, the higher likelihood of having abdominal truncal obesity amongst incident coeliacs that only worsens following treatment with a gluten-free diet together with the higher proportion of measured systolic hypertension amongst male coeliacs suggests that there are also potentially adverse vascular risk profile features associated with celiac disease.
Though incident coeliacs with silent disease reported no change in their quality of life prior to diagnosis of coeliac disease, silent coeliacs were as likely to have villous atrophy and physiological derangement to those coeliacs presenting with symptoms or with classic features of coeliac disease. The quality of life reported by coeliacs presenting with silent disease, classic disease and with gastrointestinal symptoms was worse than that observed in the general population. A year's treatment with a gluten-free diet resulted in coeliacs having similar or in some components better quality of life than that observed in the general population. The rate of change of quality of life was similar amongst those coeliacs with silent, classic or symptomatic disease.
The breast cancer risk profile suggests both protective and adverse associations of coeliac disease. The higher proportion of women being parous, having their first full-term pregnancy before 30 years and breastfeeding in addition to the younger mean age at menopause suggests women with coeliac disease have favourable breast cancer risk profile features in comparison to the general population. However, the higher likelihood of being Caucasian and of affluent social class together with higher proportion having early menarche and irregular menstrual cycles suggests there are also potentially adverse breast cancer risk profile features associated with celiac disease.
Persons with mild enteropathy disease have few physiological derangements at diagnosis of coeliac disease and show no important biochemical change following treatment with a gluten-free diet in comparison to those with severe enteropathy coeliac disease. The prevalence of hypertransaminasaemia is lower than previously reported which may be reflective of differences in study design or contemporary coeliac disease involves a milder spectrum of disease. The observed vascular and breast cancer risk profile suggests both protective and adverse associations of celiac disease and on treatment with a gluten-free diet results in an attenuation or indeed reversal of the vascular risk profile in some co-variates. Silent coeliac disease is associated with a reduction with quality in life which improves like in symptomatic and classic disease with treatment with a gluten-free diet. Incident coeliac disease is associated with more affluent social class.
Thesis (University of Nottingham only)
||Coeliac disease, Enteropathy, Disease risk factors, Gluten free diet
||W Medicine and related subjects (NLM Classification) > WD Disorders of systemic, metabolic or environmental origin
||UK Campuses > Faculty of Medicine and Health Sciences > School of Community Health Sciences
||06 Jun 2012 08:50
||13 Sep 2016 12:50
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