Functional dyspepsia; a study of two phenotypes: diabetic dyspepsia and rumination syndrome

This thesis examines several aspects of two phenotypes of a common gastrointestinal disorder known as functional dyspepsia. Functional dyspepsia has a significant effect on the quality of life of sufferers, and the societal and economic impact of evaluating and managing this disorder is considerable. Many phenotypic expressions of functional dyspepsia have been recognized, and this thesis focuses on functional dyspepsia among patients with diabetes mellitus as well as patients with rumination syndrome. These two phenotypes share several clinical features and potentially also pathogenic mechanisms. In addition, therapeutic options for patients with diabetic dyspepsia and rumination syndrome are very limited, thus representing a significant unmet need. Research into these two specific phenotypes lags behind what has been achieved in functional dyspepsia alone. For these reasons, the projects in this thesis aimed to improve the understanding of pathogenesis in these two phenotypes, but also explore potential diagnostic and therapeutic avenues. Spread over two focuses, this work in the thesis encompasses a randomised controlled trial, a case-control study and two retrospective clinical studies. The work led to novel insights into the pathophysiology of diabetic dyspepsia; we now know that intestinal chemosensitivity is a contributor to this disease. Furthermore, the experiments and studies into rumination syndrome helped unravel the mechanics of how diaphragmatic breathing treats this disorder as well as exploring potential duodenal pathogenic mechanisms. Finally, this work in this thesis discovered that oesophageal baseline impedance, as measured during an oesophageal high resolution impedance manometry study is very abnormal among patients with rumination, and indistinguishable from patients with gastroesophageal reflux disease. Overall, this work contained with this thesis makes several steps forward in our understanding of several aspects of diabetic dyspepsia and rumination syndrome.