1. Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus
- Author
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Goodarzi, Mark O, Nagpal, Tanvi, Greer, Phil, Cui, Jinrui, Chen, Yii-Der I, Guo, Xiuqing, Pankow, James S, Rotter, Jerome I, Alkaade, Samer, Amann, Stephen T, Baillie, John, Banks, Peter A, Brand, Randall E, Conwell, Darwin L, Cote, Gregory A, Forsmark, Christopher E, Gardner, Timothy B, Gelrud, Andres, Guda, Nalini, LaRusch, Jessica, Lewis, Michele D, Money, Mary E, Muniraj, Thiruvengadam, Papachristou, Georgios I, Romagnuolo, Joseph, Sandhu, Bimaljit S, Sherman, Stuart, Singh, Vikesh K, Wilcox, C Mel, Pandol, Stephen J, Park, Walter G, Andersen, Dana K, Bellin, Melena D, Hart, Phil A, Yadav, Dhiraj, and Whitcomb, David C
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Clinical Research ,Diabetes ,Genetics ,Genetic Testing ,Metabolic and endocrine ,Aged ,Case-Control Studies ,Comorbidity ,Cross-Sectional Studies ,Diabetes Mellitus ,Type 2 ,Female ,Genotype ,Humans ,Male ,Middle Aged ,Pancreatitis ,Chronic ,Polymorphism ,Single Nucleotide ,Risk Factors ,Consortium for the Study of Chronic Pancreatitis ,Diabetes ,and Pancreatic Cancer ,Clinical sciences - Abstract
IntroductionDiabetes 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.MethodsWe 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.ResultsThe 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.DiscussionRecognizing 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.
- Published
- 2019