Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus

Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)e00057
JournalClinical and translational gastroenterology
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2019

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Chronic Pancreatitis
Type 2 Diabetes Mellitus
Diabetes Mellitus
Single Nucleotide Polymorphism
Pancreatitis
Comorbidity
Pancreas
Atherosclerosis
Prospective Studies

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus. / Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC).

In: Clinical and translational gastroenterology, Vol. 10, No. 7, 01.07.2019, p. e00057.

Research output: Contribution to journalArticle

Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) 2019, 'Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus', Clinical and translational gastroenterology, vol. 10, no. 7, pp. e00057. https://doi.org/10.14309/ctg.0000000000000057
Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). / Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus. In: Clinical and translational gastroenterology. 2019 ; Vol. 10, No. 7. pp. e00057.
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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 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.",
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AU - Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)

AU - Goodarzi, Mark O.

AU - Nagpal, Tanvi

AU - Greer, Phil

AU - Cui, Jinrui

AU - Chen, Yii Der I.

AU - Guo, Xiuqing

AU - Pankow, James S.

AU - Rotter, Jerome I.

AU - Alkaade, Samer

AU - Amann, Stephen T.

AU - Baillie, John

AU - Banks, Peter A.

AU - Brand, Randall E.

AU - Conwell, Darwin L.

AU - Cote, Gregory A.

AU - Forsmark, Christopher E.

AU - Gardner, Timothy B.

AU - Gelrud, Andres

AU - Guda, Nalini

AU - LaRusch, Jessica

AU - Lewis, Michele D.

AU - Money, Mary E.

AU - Muniraj, Thiruvengadam

AU - Papachristou, Georgios I.

AU - Romagnuolo, Joseph

AU - Sandhu, Bimaljit S.

AU - Sherman, Stuart

AU - Singh, Vikesh K.

AU - Wilcox, C. Mel

AU - Pandol, Stephen J.

AU - Park, Walter G.

AU - Andersen, Dana K.

AU - Bellin, Melena D.

AU - Hart, Phil A.

AU - Yadav, Dhiraj

AU - Whitcomb, David C.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

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