Diabetes Care. 2024;47(8):1386-1394.
Higher Genetic Risk for Type 2 Diabetes Is Associated With a Faster Decline of β-Cell Function in an East Asian Population.
제1저자 이현석 · 교신저자 곽수헌
소속 (10)
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
- Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea.
- Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
- Division of Data Science Research, Innovative Biomedical Technology Research Institute, Seoul National University Hospital, Seoul, Korea.
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
- Departments of Population and Public Health Sciences and Physiology and Neuroscience, Keck School of Medicine of USC, Los Angeles, CA.
- USC Diabetes and Obesity Research Institute, Keck School of Medicine of USC, Los Angeles, CA.
- Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea.
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea.
Abstract
OBJECTIVE While most genetic variants of type 2 diabetes (T2D) are suggested to be associated with β-cell dysfunction cross sectionally, their association with the longitudinal change of β-cell function remains largely unknown.
RESEARCH DESIGN AND METHODS We analyzed data from 6,311 participants without T2D at baseline (mean [SD] age 51.6 [8.7] years) from a community-based prospective cohort in Korea. Participants underwent biennial 2-h 75-g oral glucose tolerance tests (OGTTs) during 14 years of follow-up, and the OGTT-derived disposition index (DI) was used as a marker for β-cell function. Genetic risk was quantified using the genome-wide polygenic risk score (PRS) and was stratified into low (1st quintile), intermediate (2nd-4th quintiles), and high (5th quintile) genetic risk. Lifestyle was assessed according to Life's Essential 8.
RESULTS During a mean follow-up of 10.9 years, 374 (29.6%), 851 (22.5%), and 188 (14.9%) participants developed T2D in the high, intermediate, and low genetic risk groups, respectively. Compared with the low genetic risk group, participants in the high genetic risk group had a 25% lower DI at baseline. Furthermore, in longitudinal analysis, we observed a 1.83-fold faster decline in log2-transformed DI per year (-0.034 vs. -0.019, P = 2.1 × 10-3; per 1-SD increase in T2D PRS, P = 1.2 × 10-4). Healthy lifestyle attenuated the rate of decline in DI across all genetic risk groups.
CONCLUSIONS Individuals with a higher genetic risk for T2D exhibited not only a lower OGTT-derived β-cell function at baseline but also a notably more rapid decline during follow-up. This information could be used to enable a focused precision prevention with lifestyle intervention.
© 2024 by the American Diabetes Association.
Conflict of interest statement
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- 저널
- Diabetes care · eISSN 1935-5548
- MeSH
- Adult · Female · Humans · Male · Middle Aged · Diabetes Mellitus, Type 2* / genetics / epidemiology · East Asian People / genetics · Genetic Predisposition to Disease · Glucose Tolerance Test · Insulin-Secreting Cells* / physiology · Prospective Studies · Risk Factors
- 연구비
- NHGRI NIH HHS FAIN# U01HG011723 · MD-PhD/Medical Scientist Training Program · National Research Foundation of Korea 2020R1A6A1A03047972 · NIDDK NIH HHS DK-105517 · NHGRI NIH HHS U01 HG011723 · NIDDK NIH HHS R01 DK105517
- 참고문헌
- 37편