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Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus. Clinical and translational gastroenterology Goodarzi, M. O., Nagpal, T. n., Greer, P. n., Cui, J. n., Chen, Y. I., Guo, X. n., Pankow, J. S., Rotter, J. I., Alkaade, S. n., Amann, S. T., Baillie, J. n., Banks, P. A., Brand, R. E., Conwell, D. L., Cote, G. A., Forsmark, C. E., Gardner, T. B., Gelrud, A. n., Guda, N. n., LaRusch, J. n., Lewis, M. D., Money, M. E., Muniraj, T. n., Papachristou, G. I., Romagnuolo, J. n., Sandhu, B. S., Sherman, S. n., Singh, V. K., Wilcox, C. M., Pandol, S. J., Park, W. G., Andersen, D. K., Bellin, M. D., Hart, P. A., Yadav, D. n., Whitcomb, D. C. 2019

Abstract

Diabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM.We used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin.The mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM.Recognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

View details for DOI 10.14309/ctg.0000000000000057

View details for PubMedID 31232720