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Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors

Merino, Jordi LU ; Jablonski, Kathleen A. ; Mercader, Josep M. ; Kahn, Steven E. ; Chen, Ling ; Harden, Maegan ; Delahanty, Linda M. ; Araneta, Maria Rosario G. ; Walford, Geoffrey A. and Jacobs, Suzanne B.R. , et al. (2020) In Diabetes 69(1). p.112-120
Abstract

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with... (More)

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (Pinteraction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

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publication status
published
subject
in
Diabetes
volume
69
issue
1
pages
9 pages
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:31636172
  • scopus:85077016813
ISSN
1939-327X
DOI
10.2337/db19-0097
language
English
LU publication?
yes
id
c008d023-255f-4d6c-98bc-1d6be2123b0c
date added to LUP
2020-01-03 11:56:00
date last changed
2020-01-08 08:58:29
@article{c008d023-255f-4d6c-98bc-1d6be2123b0c,
  abstract     = {<p>Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P &lt; 0.001) irrespective of CAD genetic risk (Pinteraction &gt; 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.</p>},
  author       = {Merino, Jordi and Jablonski, Kathleen A. and Mercader, Josep M. and Kahn, Steven E. and Chen, Ling and Harden, Maegan and Delahanty, Linda M. and Araneta, Maria Rosario G. and Walford, Geoffrey A. and Jacobs, Suzanne B.R. and Ibebuogu, Uzoma N. and Franks, Paul W. and Knowler, William C. and Florez, Jose C.},
  issn         = {1939-327X},
  language     = {eng},
  number       = {1},
  pages        = {112--120},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors},
  url          = {http://dx.doi.org/10.2337/db19-0097},
  doi          = {10.2337/db19-0097},
  volume       = {69},
  year         = {2020},
}