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.
Description:
Department of Oncology Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, The 8th International Medical Congress for Students and Young Doctors, September 24-26, 2020