New Diabetes Type Shown to Be Reversible after Partial Pancreatic Resection

Findings of a current study have for the first time specified in more detail which patients with pancreatic tumors that develop hyperglycemia and diabetes have improved blood glucose homeostasis after a partial pancreatic resection. The results may help physicians to more accurately assess the metabolic consequences following this surgery. The study was conducted by researchers led by Dr. Florian Ehehalt, Professor Michele Solimena and Professor Robert Grützmann from the Department of Surgery at the University Hospital Carl Gustav Carus and the Paul Langerhans Institute Dresden of Helmholtz Zentrum München at the University Hospital Carl Gustav Carus of TU Dresden, which cooperate under the umbrella of the German Center for Diabetes Research (DZD).

An association between pancreatic cancer and diabetes has been known for quite some time. Diabetes mellitus that develops secondarily to a pancreatic tumor is also called type 3c diabetes. The exact mechanism behind this association, however, has long remained an enigma. The collaboration of the Department of Surgery of the University Hospital Carl Gustav Carus under Professor Weitz and the research group Molecular Diabetology under Professor Solimena has now elucidated this mechanism. The results of their current study provide evidence for a surgically reversible type of diabetes that is to be distinguished from other types of diabetes.
On the basis of their study data, the researchers hypothesize that the cause for the development of this specific, surgically reversible diabetes type is that the pancreatic tumor compresses the adjacent bile duct. This can lead to complete or partial blockage, causing the bile to accumulate in the liver (cholestasis). As a consequence, this can impair liver function and lead to increased insulin resistance and hence to diabetes. “With our study, we describe a new type of diabetes, which is often reversible after removal of the tumor. This diabetes type is induced by an obstruction of the bile ducts in the liver which in turn causes insulin resistance,” said Professor Solimena. The authors describe this newly defined diabetes type, which is reversible after tumor resection, as “cholestasis-induced diabetes”.

Which patients can benefit in terms of improvement of diabetes?
The trial comprised 84 patients who underwent partial pancreatic resection due to chronic pancreatitis or a benign or malignant pancreatic tumor. Immediately prior to surgery and three months after that, tests were performed including a 120-minute oral glucose tolerance test (OGTT), which detected the fasting glucose value and a series of co-variables. Based on their glucose levels three months after the operation, the patients were divided into three groups: deteriorated glucose values, stable glucose values or improved glucose values.
Patients who benefited from a partial pancreatic resection in terms of their glucose homeostasis displayed a pathological oral glucose tolerance prior to the operation; the diagnosis of a glucose dysregulation took place less than six months before the operation. Most of the patients were older than 50 years, and the serum markers for a tumor, acute pancreatitis, obstruction of the bile duct und liver cell damage were elevated prior to surgery. These normalized postoperatively, regardless of the type of pancreatic tumor.
However, no improvement of glucose metabolism by partial pancreatic resection could be detected in patients with chronic pancreatitis or left-sided resection of the pancreas.

Conclusions of the authors
According to the authors, the results of this trial can help physicians make a more exact prognosis of the postoperative metabolic consequences of a pancreatic resection and enable them to better inform the affected patients. In addition, the study complements previous findings on the association of diabetes and pancreatic cancer and shows that the tumor itself can induce hyperglycemia due to liver cell damage. Furthermore, a temporary control of the bile duct, the pancreas and liver cell parameters during the first months following the diagnosis of a glucose metabolism disturbance in patients older than 50 years could function as an efficient and practical filter for the screening for pancreatic tumors. The authors conclude that further studies are required to confirm these findings.

Ehehalt F et al. Blood Glucose Homeostasis in the Course of Partial Pancreatectomy – Evidence for Surgically Reversible Diabetes Induced by Cholestasis. PLoS One 2015; 10(8): e0134140. DOI: 10.1371/journal.pone.0134140

Further information on type 3c diabetes: