Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer

Abstract

Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps.

A Chromatin Basis for Cell Lineage and Disease Risk in the Human Pancreas

“…In addition to enrichment of GWAS SNPs to islet endocrine gene DORs, we found diabetes-related SNPs overlapping with exocrine specific DORs, suggesting future studies to assess the possibility that pancreatic exocrine cell dysfunction could impair islet glucose sensing or insulin output. There is strong evidence that exocrine pancreas growth (Campbell-Thompson et al, 2012), or diseases like chronic pancreatitis, cystic fibrosis and pancreatic adenocarcinoma are linked to multiple forms of diabetes (Hart et al, 2016). Our findings provide a chromatin-based framework to investigate the genetic basis of these pancreatic exocrine-endocrine disease associations.…”

Patient and Disease Characteristics Associated With the Presence of Diabetes Mellitus in Adults With Chronic Pancreatitis in the United States

“…However, the risk for DM in those who have CP is much higher than the general population. The prevalence of DM in CP has been estimated anywhere between 25 and 80% (6). Increasing age, pancreatic calcifications, and prior pancreatic surgery have emerged as factors potentially conveying a higher risk for DM (7–10).…”

Complications of Chronic Pancreatitis

“…Currently, the diabetes subtypes associated with exocrine disease of the pancreas (including CP) are collectively referred to as pancreatogenic or type 3c diabetes mellitus (T3cDM) [2]. Although T3cDM is a common name for the various subtypes, the mechanisms of hyperglycemia can differ substantially among the various types of pancreatic disease.…”

“…It is estimated that approximately 5% of all DM is attributable to T3cDM, but the true prevalence has not been elucidated [2]. For example, in the largest single-center study to assess the prevalence of T3cDM among a cohort of diabetics, the prevalence was approximately 9%; however, the presence of pancreatic disease was determined based on an abnormal fecal elastase level, which is only fairly accurate for the diagnosis of mild CP [3, 4].…”