Abstract:
Metabolic abnormalities are an important and frequent sequela of acute pancreatitis. Diabetes after diseases of the exocrine pancreas has only been recently highlighted as a distinct clinical entity under the collective term of diabetes mellitus. However, the majority of evidence in this field has been in the context of chronic pancreatitis or pancreatic cancer, with research frontiers rarely extending to newonset diabetes after acute pancreatitis. Although research is beginning to gain momentum in this field, lipid metabolism and adipocytokines after acute pancreatitis have received a relative paucity of attention. The first aim of the thesis was to assess associations between adipocytokines and glucose metabolism after acute pancreatitis. The second was to study the relationship between adipocytokines and pancreatic hormones after acute pancreatitis. Last, this thesis aimed to evaluate lipid metabolism in patients with impaired glucose homeostasis after acute pancreatitis. All three studies investigated a cohort of 83 patients after acute pancreatitis, adjusting for a range of patient- and pancreatitis-related factors in multi-level statistical modeling. The results of this thesis first demonstrated that interleukin-6 was significantly associated with chronic hyperglycemia and insulin resistance - likely due to the release of interleukin-6 during the inflammatory process of acute pancreatitis, which then drives and sustains hyperglycemia. Next, several significant associations were found between adipocytokines and pancreatic hormones. Those with particular relevance to glucose metabolism after acute pancreatitis were between insulin and interleukin-6, and amylin and both monocyte chemoattractant protein-1 and tumor necrosis factor-α. Here, it is posited that interleukin-6 might lead to hyperinsulinaemia through reducing insulin clearance. Second, monocyte chemoattractant protein-1 and tumor necrosis factor-α were suggested to stimulate the release of amylin, which may have implications for future amyloid deposition and insulin sensitivity. Last, chronic hyperglycemia after acute pancreatitis was significantly associated with elevated serum glycerol and triglycerides, indicating upregulated lipolysis in patients after acute pancreatitis. This thesis has paved the path for further research opportunities to better understand mechanisms underlying the pathogenesis of diabetes after acute pancreatitis. In turn, this could translate to clinical significance through identifying novel biomarkers and redefining treatment paradigms to prevent metabolic abnormalities developing after diseases of the exocrine pancreas.