Pancreatogenic Diabetes: Special Considerations for Management

Background/Aims: Pancreatogenic, or type 3c, diabetes (T3cDM) occurs due to inherited or acquired pancreatic disease or resection. Although similar to the more prevalent type 1 and type 2 diabetes, pancreatogenic diabetes has a unique pattern of hormonal and metabolic characteristics and a high incidence of pancreatic carcinoma in the majority of patients with T3cDM. Despite these differences, no guidelines for therapy have been described. Methods: Published studies on the prevalence, pathophysiology, and cancer associations of T3cDM were reviewed. The recent studies on the protective role and mechanism of metformin therapy as both an anti-diabetic and anti-neoplastic agent were reviewed, and studies on the cancer risk of other anti-diabetic drugs were surveyed. Results: T3cDM accounts for 5-10% of Western diabetic populations and is associated with mild to severe disease. Hepatic insulin resistance is characteristic of T3cDM and is caused by deficiencies of both insulin and pancreatic polypeptide. 75% of T3cDM is due to chronic pancreatitis, which carries a high risk for pancreatic carcinoma. Insulin and insulin secretagogue treatment increases the risk of malignancy, whereas metformin therapy reduces it. Pancreatic exocrine insufficiency associated with T3cDM contributes to nutritional deficiencies and the development of metabolic bone disease. Conclusions: Until consensus recommendations are reached, the glycemic treatment of T3cDM should avoid insulin and insulin secretagogues if possible. Metformin should be the first line of therapy, and continued if insulin treatment must be added for adequate glucose control. Pancreatic enzyme therapy should be added to prevent secondary nutritional and metabolic complications.