Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes

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Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes. / Billings, Liana K; Jablonski, Kathleen A; Pan, Qing; Franks, Paul W; Goldberg, Ronald B; Hivert, Marie-France; Kahn, Steven E; Knowler, William C; Lee, Christine G; Merino, Jordi; Huerta-Chagoya, Alicia; Mercader, Josep M; Raghavan, Sridharan; Shi, Zhuqing; Srinivasan, Shylaja; Xu, Jianfeng; Florez, Jose C; Udler, Miriam S.

In: Diabetes, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Billings, LK, Jablonski, KA, Pan, Q, Franks, PW, Goldberg, RB, Hivert, M-F, Kahn, SE, Knowler, WC, Lee, CG, Merino, J, Huerta-Chagoya, A, Mercader, JM, Raghavan, S, Shi, Z, Srinivasan, S, Xu, J, Florez, JC & Udler, MS 2024, 'Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes', Diabetes. https://doi.org/10.2337/db23-0761

APA

Billings, L. K., Jablonski, K. A., Pan, Q., Franks, P. W., Goldberg, R. B., Hivert, M-F., Kahn, S. E., Knowler, W. C., Lee, C. G., Merino, J., Huerta-Chagoya, A., Mercader, J. M., Raghavan, S., Shi, Z., Srinivasan, S., Xu, J., Florez, J. C., & Udler, M. S. (2024). Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes. Diabetes. https://doi.org/10.2337/db23-0761

Vancouver

Billings LK, Jablonski KA, Pan Q, Franks PW, Goldberg RB, Hivert M-F et al. Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes. Diabetes. 2024. https://doi.org/10.2337/db23-0761

Author

Billings, Liana K ; Jablonski, Kathleen A ; Pan, Qing ; Franks, Paul W ; Goldberg, Ronald B ; Hivert, Marie-France ; Kahn, Steven E ; Knowler, William C ; Lee, Christine G ; Merino, Jordi ; Huerta-Chagoya, Alicia ; Mercader, Josep M ; Raghavan, Sridharan ; Shi, Zhuqing ; Srinivasan, Shylaja ; Xu, Jianfeng ; Florez, Jose C ; Udler, Miriam S. / Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes. In: Diabetes. 2024.

Bibtex

@article{cec2256120e84cff9a1ef8a4af524d27,
title = "Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes",
abstract = "Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the influence of T2D pPS on diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin or placebo arms. Associations were tested using general linear models and Cox regression adjusted for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher β-cell pPS was associated with lower insulinogenic index and corrected insulin response at one year follow-up adjusted for baseline measures (effect per pPS standard deviation (SD) -0.04, P=9.6 x 10-7; -8.45 uU/mg, P=5.6 x 10-6, respectively) and with increased diabetes incidence adjusted for BMI at nominal significance (HR 1.10 per SD, P=0.035). The liver/lipid pPS was associated with reduced one-year baseline-adjusted triglyceride levels (effect per SD -4.37, P=0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the β-cell cluster pPS had worsening in measures of β-cell function.",
author = "Billings, {Liana K} and Jablonski, {Kathleen A} and Qing Pan and Franks, {Paul W} and Goldberg, {Ronald B} and Marie-France Hivert and Kahn, {Steven E} and Knowler, {William C} and Lee, {Christine G} and Jordi Merino and Alicia Huerta-Chagoya and Mercader, {Josep M} and Sridharan Raghavan and Zhuqing Shi and Shylaja Srinivasan and Jianfeng Xu and Florez, {Jose C} and Udler, {Miriam S}",
note = "{\textcopyright} 2024 by the American Diabetes Association.",
year = "2024",
doi = "10.2337/db23-0761",
language = "English",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",

}

RIS

TY - JOUR

T1 - Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes

AU - Billings, Liana K

AU - Jablonski, Kathleen A

AU - Pan, Qing

AU - Franks, Paul W

AU - Goldberg, Ronald B

AU - Hivert, Marie-France

AU - Kahn, Steven E

AU - Knowler, William C

AU - Lee, Christine G

AU - Merino, Jordi

AU - Huerta-Chagoya, Alicia

AU - Mercader, Josep M

AU - Raghavan, Sridharan

AU - Shi, Zhuqing

AU - Srinivasan, Shylaja

AU - Xu, Jianfeng

AU - Florez, Jose C

AU - Udler, Miriam S

N1 - © 2024 by the American Diabetes Association.

PY - 2024

Y1 - 2024

N2 - Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the influence of T2D pPS on diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin or placebo arms. Associations were tested using general linear models and Cox regression adjusted for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher β-cell pPS was associated with lower insulinogenic index and corrected insulin response at one year follow-up adjusted for baseline measures (effect per pPS standard deviation (SD) -0.04, P=9.6 x 10-7; -8.45 uU/mg, P=5.6 x 10-6, respectively) and with increased diabetes incidence adjusted for BMI at nominal significance (HR 1.10 per SD, P=0.035). The liver/lipid pPS was associated with reduced one-year baseline-adjusted triglyceride levels (effect per SD -4.37, P=0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the β-cell cluster pPS had worsening in measures of β-cell function.

AB - Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the influence of T2D pPS on diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin or placebo arms. Associations were tested using general linear models and Cox regression adjusted for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher β-cell pPS was associated with lower insulinogenic index and corrected insulin response at one year follow-up adjusted for baseline measures (effect per pPS standard deviation (SD) -0.04, P=9.6 x 10-7; -8.45 uU/mg, P=5.6 x 10-6, respectively) and with increased diabetes incidence adjusted for BMI at nominal significance (HR 1.10 per SD, P=0.035). The liver/lipid pPS was associated with reduced one-year baseline-adjusted triglyceride levels (effect per SD -4.37, P=0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the β-cell cluster pPS had worsening in measures of β-cell function.

U2 - 10.2337/db23-0761

DO - 10.2337/db23-0761

M3 - Journal article

C2 - 38758294

JO - Diabetes

JF - Diabetes

SN - 0012-1797

ER -

ID: 392704587