Journal
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
Volume 10, Issue -, Pages -Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.14309/ctg.0000000000000057
Keywords
-
Categories
Funding
- NIH [R01 DK061451, R01 DK077906, U01 DK108314, U01 DK108327, U01 DK108320, U01 DK108306, U01 DK108323, P30 DK063491]
- Eris M. Field Chair in Diabetes Research
- National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR024153, UL1TR000005]
- NIH Roadmap for Medical Research (University of Pittsburgh)
- National Heart, Lung, and Blood Institute (NHLBI)
- NHLBI [N02-HL-64278]
- [HHSN268201500003I]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-000040]
- [UL1-TR-001079]
- [UL1-TR-001420]
- [UL1-TR-001881]
- [DK063491]
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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, P = 0.95), and theGRS 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.
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