Strengthening the Role of Iron After Pancreatitis

Abstract

Iron is implicated in the pathogenesis of metabolic abnormalities, even in the absence of overt derangements. The liver plays an important role in iron and glucose metabolism. Linking the endocrine and exocrine pancreas, the pathogenesis of metabolic abnormalities after pancreatitis continues to be actively investigated. However, the associations between iron metabolism, diabetes of the exocrine pancreas, and liver disease (LD) after pancreatitis are yet to be investigated. The first aim of this thesis was to investigate the associations between iron metabolism and deranged glucose metabolism in a clinical study of patients after acute pancreatitis (AP). The second aim was to investigate the role of chronic low-grade inflammation in associations between iron metabolism and deranged glucose metabolism in a clinical study of patients after AP. Last, this thesis aimed to investigate incidence of LD and factors associated with it in a New Zealand-wide population-based cohort study of more than 20,000 patients with an episode of pancreatitis. The above studies adjusted for a range of patient- and pancreatitis-related factors in multi-level statistical modelling. The results of this thesis first showed that hepcidin was significantly increased and ferritin was significantly decreased in patients with chronic hyperglycaemia after AP. It is posited that elevated hepcidin may have an adaptive role through prevention of iron uptake. Second, lipopolysaccharide binding protein was significantly associated with hepcidin and ferritin, and interleukin-6 was significantly associated with hepcidin, indicating interplay between chronic low-grade inflammation and iron metabolism in patients after AP. Last, there was a stepwise increase in LD incidence in patients who progress from first episode of AP to chronic pancreatitis and the number of pancreatitis recurrences was a significant risk factor for LD, irrespective of iron metabolism disorders. This indicates that pancreatitis should be better regarded as a risk factor for LD. This thesis provides insight into the associations between iron and pancreatitis sequalae in the aim to elucidate the pathogenesis of metabolic abnormalities after pancreatitis. Furthermore, it paves the path for future research to better understand mechanisms underlying these associations in an attempt to prevent and treat diabetes of the exocrine pancreas and LD after pancreatitis.