Challenges of Managing Type 3c Diabetes in the Context of Pancreatic Resection, Cancer and Trauma

Abstract

Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic or pancreoprivic diabetes, is a specific type of DM that often develops as a result of diseases affecting the exocrine pancreas, exhibiting an array of hormonal and metabolic characteristics. Several pancreatic exocrine diseases and surgical procedures may cause T3cDM. Diagnosing T3cDM remains difficult as the disease characteristics frequently overlap with clinical presentations of type 1 DM (T1DM) or type 2 DM (T2DM). Managing T3cDM is likewise challenging due to numerous confounding metabolic dysfunctions, including pancreatic endocrine and exocrine insufficiencies and poor nutritional status. Treatment of pancreatic exocrine insufficiency is of paramount importance when managing patients with T3cDM. This review aims to consolidate the latest information on surgical etiologies of T3cDM, focusing on partial pancreatic resections, total pancreatectomy, pancreatic cancer and trauma.

Keywords: insulin; pancreas; pancreatic cancer; pancreatic resection; partial pancreatectomy; total pancreatectomy; trauma; type 3c diabetes mellitus.

Figure 1

Graphical abstract. This review aims to consolidate the latest information on understudied etiologies of T3cDM, focusing on partial pancreatic resections, total pancreatectomy, pancreatic cancer, and trauma.

Figure 2

Surgical methods for pancreatectomy, locations of cancer in the pancreas and grading for pancreatic trauma. The choice of pancreatic surgery is based on the underlying cause and the relevant pancreatic anatomy. The pancreas can be broadly divided into head, body and tail regions. (A) Partial pancreatectomy (PP) involves resecting either: (i) the head region in combination with some of the surrounding organs (e.g., pancreaticoduodenectomy, PD); (ii) the body region (for a central pancreatectomy, which is not commonly performed); or (iii) the tail region for a distal pancreatectomy (DP, sometimes performed in combination with the body region). (B) A total pancreatectomy (TP), often used to treat chronic pancreatitis and pancreatic cancers, is a complex surgical procedure where the entire diseased pancreas is excised, and involves removal of other surrounding organs, vessels and lymph nodes. One of the major limitations of this procedure is life-long dependence on exogenous insulin and enzyme replacements. (C) T3cDM is a major challenge after a TP procedure. In some cases, a simultaneous islet auto transplantation (IAT) procedure is performed after TP. This dual TPIAT therapy helps to preserve endogenous beta cells and insulin secretion to alleviate post-TP-induced DM. For IAT, the remaining functional islet cells from a diseased organ are recovered by digesting the pancreas with tissue dissociation enzymes to obtain an islet equivalent volume. The harvested islet autografts are then reimplanted into the host liver via portal vein infusion. (D) In the context of pancreatic cancers, a tumor can originate in the head, body or tail regions of the pancreas. The development of T3cDM can occur anywhere along the progression of disease spectrum, beginning with an inflammatory insult. Some types of pancreatic cancers include the Pancreatic Ductal Adeno Carcinoma (PDAC), pancreatic NeuroEndocrine Tumors (pNETs), Intraductal Papillary Mucinous Neoplasms (IPMNs) and the Mucinous Cystic Neoplasms. (E) T3cDM can also occur after pancreatic trauma, with traumatic injuries graded (1–5) based on the severity of the injury.