Structure and function of the exocrine pancreas in patients with type 1 diabetes

In the last 10 years, several studies have shown that the pancreas of patients with type 1 diabetes (T1D), and even of subjects at risk for T1D, was smaller than the pancreas from healthy subjects. This arose the question of the relationships between the endocrine and exocrine parts of the pancreas in T1D pathogenesis. Our review underlines that histological anomalies of the exocrine pancreas are common in patients with T1D: intralobular and interacinar fibrosis, acinar atrophy, fatty infiltration, leucocytic infiltration, and pancreatic arteriosclerosis are all frequent observations. Moreover, 25% to 75% of adult patients with T1D present with pancreatic exocrine dysfunction. Our review summarizes the putative causal factors for these structural and functional anomalies, including: 1/ alterations of insulin, glucagon, somatostatin and pancreatic polypeptide secretion, 2/ global pancreatic inflammation 3/ autoimmunity targeting the exocrine pancreas, 4/ vascular and neural abnormalities, and 5/ the putative involvement of pancreatic stellate cells. These observations have also given rise to new theories on T1D: the primary event of T1D pathogenesis could be non-specific, e.g bacterial or viral or chemical, resulting in global pancreatic inflammation, which in turn could cause beta-cell predominant destruction by the immune system. Finally, this review emphasizes that it is advisable to evaluate pancreatic exocrine function in patients with T1D presenting with gastro-intestinal complaints, as a clinical trial has shown that pancreatic enzymes replacement therapy can reduce the frequency of hypoglycemia and thus might improve quality of life in subjects with T1D and exocrine failure.