Blood Glucose Homeostasis in the Course of Partial Pancreatectomy--Evidence for Surgically Reversible Diabetes Induced by Cholestasis

PLoS One. 2015 Aug 6;10(8):e0134140. doi: 10.1371/journal.pone.0134140. eCollection 2015.

Abstract

Background and aim: Partial pancreatic resection is accompanied not only by a reduction in the islet cell mass but also by a variety of other factors that are likely to interfere with glucose metabolism. The aim of this work was to characterize the patient dynamics of blood glucose homeostasis during the course of partial pancreatic resection and to specify the associated clinico-pathological variables.

Methods: In total, 84 individuals undergoing elective partial pancreatic resection were consecutively recruited into this observational trial. The individuals were assigned based on their fasting glucose or oral glucose tolerance testing results into one of the following groups: (I) deteriorated, (II) stable or (III) improved glucose homeostasis three months after surgery. Co-variables associated with blood glucose dynamics were identified.

Results: Of the 84 participants, 25 (30%) displayed a normal oGTT, 17 (20%) showed impaired glucose tolerance, and 10 (12%) exhibited pathological glucose tolerance. Elevated fasting glucose was present in 32 (38%) individuals before partial pancreatic resection. Three months after partial pancreatic resection, 14 (17%) patients deteriorated, 16 (19%) improved, and 54 (64%) retained stable glucose homeostasis. Stability and improvement was associated with tumor resection and postoperative normalization of recently diagnosed glucose dysregulation, preoperatively elevated tumor markers and markers for common bile duct obstruction, acute pancreatitis and liver cell damage. Improvement was linked to preoperatively elevated insulin resistance, which normalized after resection and was accompanied by a decrease in fasting- and glucose-stimulated insulin secretion.

Conclusions: Surgically reversible blood glucose dysregulation diagnosed concomitantly with a (peri-) pancreatic tumor appears secondary to compromised liver function due to tumor compression of the common bile duct and the subsequent increase in insulin resistance. It can be categorized as "cholestasis-induced diabetes" and thereby distinguished from other forms of hyperglycemic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Tumor-Associated, Carbohydrate / blood
  • Blood Glucose / analysis
  • Body Mass Index
  • Cholestasis / complications
  • Cholestasis / pathology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / surgery*
  • Female
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Middle Aged
  • Pancreas / metabolism
  • Pancreatectomy
  • Pancreatitis, Chronic / metabolism
  • Pancreatitis, Chronic / pathology
  • Pancreatitis, Chronic / surgery*

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • carbohydrate antigen 199, human
  • hemoglobin A1c protein, human
  • Glucose

Grants and funding

The work leading to this publication received support from the German Center for Diabetes Research, which is supported by the German Ministry for Education and Research, and from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 155005 (IMIDIA), the resources of which are composed of financial contributions from the European Union's Seventh Framework Program (FP7/2007-2013) and the kind contributions from EFPIA companies.