A1 Journal article (refereed)
Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women (2024)
Selenius, J. S., Silveira, P. P., Bonsdorff, M. V., Lahti, J., Koistinen, H., Koistinen, R., Seppälä, M., Eriksson, J. G., & Wasenius, N. S. (2024). Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women. Diabetes & Metabolism Journal, Early online. https://doi.org/10.4093/dmj.2023.0039
JYU authors or editors
Publication details
All authors or editors: Selenius, Jannica S.; Silveira, Patricia P.; Bonsdorff, Mikaela von; Lahti, Jari; Koistinen, Hannu; Koistinen, Riitta; Seppälä, Markku; Eriksson, Johan G.; Wasenius, Niko S.
Journal or series: Diabetes & Metabolism Journal
ISSN: 2233-6079
eISSN: 2233-6087
Publication year: 2024
Publication date: 25/03/2024
Volume: Early online
Publisher: Korean Diabetes Association
Publication country: Korea, Republic of (South Korea)
Publication language: English
DOI: https://doi.org/10.4093/dmj.2023.0039
Publication open access: Openly available
Publication channel open access: Open Access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/94530
Abstract
To investigate associations between variations in the co-expression-based brain insulin receptor polygenic score and cardiometabolic risk factors and diabetes mellitus.
Methods
This cross-sectional study included 1,573 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Cardiometabolic markers included body composition, waist circumference, circulating lipids, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 1 and 3 (IGFBP-1 and -3). Glucose and insulin levels were measured during a standardized 2-hour 75 g oral glucose tolerance test and impaired glucose regulation status was defined by the World Health Organization 2019 criteria. Analyzes were adjusted for population stratification, age, smoking, alcohol consumption, socioeconomic status, chronic diseases, birth weight, and leisure-time physical activity.
Results
Multinomial logistic regression indicated that one standard deviation increase in hePRS-IR was associated with increased risk of diabetes mellitus in all participants (adjusted relative risk ratio, 1.17; 95% confidence interval, 1.01 to 1.35). In women, higher hePRS-IR was associated with greater waist circumference and higher body fat percentage, levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, insulin, and IGFBP-1 (all P≤0.02). The mePRS-IR was associated with decreased IGF-1 level in women (P=0.02). No associations were detected in men and studied outcomes.
Conclusion
hePRS-IR is associated with sex-specific differences in cardiometabolic risk factor profiles including impaired glucose regulation, abnormal metabolic markers, and unfavorable body composition in women.
Keywords: diabetes; cardiovascular diseases; risk factors; biomarkers; lipid metabolism; body composition; gender differences
Free keywords: cardiometabolic risk factors; diabetes mellitus; lipid metabolism
Contributing organizations
Ministry reporting: Yes
Preliminary JUFO rating: 1
