Type 3C (pancreatogenic) diabetes mellitus

Abstract

Introduction. Exocrine pancreatic insufficiency is frequently associated with diabetes, with high prevalence in both insulin-dependent or insulin-independent patients. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic diabetes mellitus, but recent literature refers to it as type 3c diabetes as it was classified by American Diabetes Association. Aim of the study. De-novo diabetes mellitus is an important consequence of distal pancreatectomy, ductal adenocarcinoma, chronic pancreatitis and a better understanding of the frequency and risk factors for this outcome may allow alteration of the treatment course. Our goal involves identifying causes and differences between some entities of type 3c diabetes mellitus Materials and methods.. The following represents a summary of the relevant literature in electronic databases, with the purpose of providing more insight into the important relationships between pancreatic ductal adenocarcinoma (PDAC), distal pancreatomy and chronic pancreatitis with diabetes. Relevant literature cited in electronic databases Scopus, EMBASE, MEDLINE, Web of Science, The Nature, The Lancet. Results. Even if in case of distal pancreatectomy etiology may be clear-absence of islets leads to lowering of the insulin, there are however some specifics: Due to an increased peripheral sensitivity to insulin and the reduced glucagon level in pancreatogenic diabetes, exogenous insulin administration frequently causes hypoglycemic attacks, characteristically called ‘brittle’ diabetes. On the other side low levels of pancreatic polypeptide raises blood glucose level drastically. In chronic pancreatitis (CP) inflammatory environment and increased concentration of pro-inflammatory cytokines such interleukin 1β, 1R, tumor necrosis factor (TNF) α and agents like adrenomedullin or vanin-1 within the pancreatic parenchyma mediate β-cell dysfunction before frank β-cell loss. As chronic pancreatitis progresses, the extensive fibrosis of the exocrine pancreas slowly destroys the pancreatic islet tissue. Moreover, deficiency of the Pancreatic polypeptide, which regulates the expression and availability of hepatic insulin receptors, leads to persistent hepatic glucose production that makes hyperglycemia more severe, fact that proves the observation that insulin resistance in CP appears to be independent of other components of the metabolic syndrome. On the other hand, in pancreatic ductal adenocarcinoma (DA), due to glandular destruction hypoinsulinemia would be expected, however, diabetes secondary to pancreatic cancer is associated with hyperinsulinaemia secondary to insulin resistance. This may be due to raised circulating level of islet amyloid polypeptide (IAPP), also known as amylin, which reduces insulin sensitivity in vivo and glycogen synthesis in vitro, that are found to be higher in patients with DA, although pancreatic tumors expressed neither IAPP nor insulin. It has been suggested that supernatant from cell lines of pancreatic ductal adenocarcinoma has been playing a key role in insulin modulation. Conclusions. Despite the potential resemblance to type 1 and type 2 diabetes, pancreatogenic diabetes has a unique structure of hormonal and metabolic characteristics; it is rated as unique clinical and metabolic unit. Clinical features are closely related to pathogenetic ones. Due to abnormal incretin response and cranky effect of PP and amylin the question of peripheral sensitivity to insulin, since it is closely related to the problem of antihyperglycemic therapy, is still open. The development and improvement of new technologies such as islet autotransplantation in liver, PP replacement, and artificial endocrine pancreas will help to provide better glycemic control in patients with type 3c diabetes.