Citations 1
Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus
Goodarzi, Mark O. , Nagpal, Tanvi, Greer, Phil J. , Cui, Jinrui, Chen, Yii‐Der I., Pankow, James S. , Rotter, Jerome I. , Alkaade, Samer, Amann, Stephen T. , Baillie, John , Banks, Peter A. , Conwell, Darwin L. , Coté, Gregory A. , Forsmark, Christopher E., Gardner, Timothy B. , Gelrud, Andrés , Guda, Nalini M. , LaRusch, Jessica, Lewis, Michele D. , Money, Mary E. , Muniraj, Thiruvengadam , Romagnuolo, Joseph , Sandhu, Bimaljit S., Sherman, Stuart , Wilcox, C. Mel, Park, Walter G. , Andersen, Dana K. , Hart, Phil A. , Yadav, Dhiraj , Whitcomb, David C. , Whitcomb, David C , Rotter, Jerome I , Pankow, James S , Lewis, Michele D , Nagpal, Tanvi, Guo, Xiuqing , Brand, Randall E. , Papachristou, Georgios I. , Singh, Vikesh K. , Pandol, Stephen J. , Bellin, Melena D.
Clinical and Translational Gastroenterology | June 22, 2019 | Volume: 10 | Issue: 7 | Pages: e00057
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 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. 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 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. 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.