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Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study
OBJECTIVE: Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management. METHODS: We tested the shape...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714469/ https://www.ncbi.nlm.nih.gov/pubmed/36465637 http://dx.doi.org/10.3389/fendo.2022.1009095 |
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author | Ma, Yujia Zhou, Zechen Li, Xiaoyi Ding, Kexin Xiao, Han Wu, Yiqun Wu, Tao Chen, Dafang |
author_facet | Ma, Yujia Zhou, Zechen Li, Xiaoyi Ding, Kexin Xiao, Han Wu, Yiqun Wu, Tao Chen, Dafang |
author_sort | Ma, Yujia |
collection | PubMed |
description | OBJECTIVE: Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management. METHODS: We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes. RESULTS: Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72–0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258). CONCLUSIONS: We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal. |
format | Online Article Text |
id | pubmed-9714469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97144692022-12-02 Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study Ma, Yujia Zhou, Zechen Li, Xiaoyi Ding, Kexin Xiao, Han Wu, Yiqun Wu, Tao Chen, Dafang Front Endocrinol (Lausanne) Endocrinology OBJECTIVE: Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management. METHODS: We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes. RESULTS: Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72–0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258). CONCLUSIONS: We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal. Frontiers Media S.A. 2022-11-17 /pmc/articles/PMC9714469/ /pubmed/36465637 http://dx.doi.org/10.3389/fendo.2022.1009095 Text en Copyright © 2022 Ma, Zhou, Li, Ding, Xiao, Wu, Wu and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Ma, Yujia Zhou, Zechen Li, Xiaoyi Ding, Kexin Xiao, Han Wu, Yiqun Wu, Tao Chen, Dafang Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study |
title | Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study |
title_full | Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study |
title_fullStr | Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study |
title_full_unstemmed | Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study |
title_short | Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study |
title_sort | linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: the spurious u–curve in observational study |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714469/ https://www.ncbi.nlm.nih.gov/pubmed/36465637 http://dx.doi.org/10.3389/fendo.2022.1009095 |
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