Genetic risk score in diabetes associated with chronic pancreatitis versus type 2 diabetes mellitus

Mark O. Goodarzi, Tanvi Nagpal, Phil Greer, Jinrui Cui, Yii Der I. Chen, Xiuqing Guo, James S. Pankow, Jerome I. Rotter, Samer Alkaade, Stephen T. Amann, John Baillie, Peter A. Banks, Randall E. Brand, Darwin L. Conwell, Gregory A. Cote, Christopher E. Forsmark, Timothy B. Gardner, Andres Gelrud, Nalini Guda, Jessica LaRuschMichele D. Lewis, Mary E. Money, Thiruvengadam Muniraj, Georgios I. Papachristou, Joseph Romagnuolo, Bimaljit S. Sandhu, Stuart Sherman, Vikesh K. Singh, C. MelWilcox, Stephen J. Pandol, Walter G. Park, Dana K. Andersen, Melena D. Bellin, Phil A. Hart, Dhiraj Yadav, David C. Whitcomb

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

INTRODUCTION: 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 froma 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. METHODS: 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. RESULTS: The mean GRSwas identical between 321 subjects with CP-DM and 423 subjects withT2DM(66.53 vs 66.42, P50.95), and theGRS of both diabetic groups was significantly higher than that of nondiabetic controls (n 5 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 pancreasspecific 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. DISCUSSION: 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.

Original languageEnglish (US)
Article numbere-00057
JournalClinical and translational gastroenterology
Volume10
Issue number7
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Gastroenterology

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    Goodarzi, M. O., Nagpal, T., Greer, P., Cui, J., Chen, Y. D. I., Guo, X., Pankow, J. S., Rotter, J. I., Alkaade, S., Amann, S. T., Baillie, J., Banks, P. A., Brand, R. E., Conwell, D. L., Cote, G. A., Forsmark, C. E., Gardner, T. B., Gelrud, A., Guda, N., ... Whitcomb, D. C. (2019). Genetic risk score in diabetes associated with chronic pancreatitis versus type 2 diabetes mellitus. Clinical and translational gastroenterology, 10(7), [e-00057]. https://doi.org/10.14309/ctg.0000000000000057