Chronic pancreatitis and diabetes mellitus: a review of the literature

Abstract

Background: For a long time there has been a discussion about how chronic pancreatitis (CP) and diabetes mellitus (DM) are related to each other. If a patient has both conditions, should they be viewed as two separate disorders, or one of them is a plausible consequence of the other? If the latter is true, what are pathophysiological mechanisms of DM in CP? Current consensus documents by specialists in pancreatic diseases pay little attention to this issue, and their main statements have low level of evidence. The Russian consensus on the diagnosis and treatment of CP (2016) contains no statements on DM. In the Russian guidelines and consensus documents to be developed, it is necessary to include provisions on the pancreatogenic DM as an independent “other type DM’, with consideration of its pathophysiological mechanisms and clinical particulars.Aim: To characterize the state-of-the-art in pancreatogenic DM, to demonstrate its differences from DM types 1 and 2 from pathogenetic and clinical perspectives.Methods: The review is based on the results of meta-analyses, systematic reviews and main provisions of the existing clinical guidelines and consensus documents available from PubMed and E-library.Results: According to various sources, Type 3c DM, or latent impaired glucose tolerance in CP, can eventually develop in 25 to 80% patients with CP. Impaired glucose tolerance is found in 40 to 60% of patients with acute pancreatitis, with persistent hyperglycemia after acute episode seen in 15 to 18% of the patients. Exocrine pancreatic insufficiency is commonly seen in Type 1 and Type 2 diabetic patients, although the data on its prevalence are highly contradictory indicating a lack of knowledge in the field. Type 3c DM is characterized by its manifestation at later stages of CP, concomitant excretory deficiency of the pancreas, brittle course with proneness to hypoglycemia and no ketoacidosis. The highest risk group includes patients with longstanding CP, previous partial pancreatic resection and patients with early calcifying pancreatitis, mainly of the alcoholic origin. Optimal and rational medical treatment of pancreatogenic DM still remains disputable, while the evidence base of the efficacy and safety of various anti-diabetic agents in this disease is lacking, and no consensus on the issue has been yet reached. General treatment guidelines given in a number of international consensus documents are limited to cautious insulin administration.Conclusion: Pancreatogenic DM differs from Type 1 and Type 2 DM in a number of aspects, namely, mechanisms of hyperglycemia, hormonal profiles, clinical particulars and treatment approaches. Endocrine pancreatic insufficiency in CP is caused by secondary inflammatory injury of the pancreatic islets. The key to specifics of Type 3c DM lies in anatomical and physiological interplay of the exocrine and endocrine compartments of the pancreas. At presents, most provisions on pancreatogenic DM are empirical and seem to be rather declarative, because intrinsic mechanisms of this type of diabetes and moreover its pathogenetically based treatment have been poorly studied. Nevertheless, all patients with CP or other pancreatic diseases should be assessed for pancreatogenic DM.