Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study
Abstract Background Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-06-01
|
| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-022-01540-6 |
| _version_ | 1811242294930571264 |
|---|---|
| author | Sizhi Ai Xiaoyu Wang Shanshan Wang Yilin Zhao Shuxun Guo Guohua Li Zhigang Chen Fei Lin Sheng Guo Yan Li Jihui Zhang Guoan Zhao |
| author_facet | Sizhi Ai Xiaoyu Wang Shanshan Wang Yilin Zhao Shuxun Guo Guohua Li Zhigang Chen Fei Lin Sheng Guo Yan Li Jihui Zhang Guoan Zhao |
| author_sort | Sizhi Ai |
| collection | DOAJ |
| description | Abstract Background Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level are causally associated with cardiac structure and function remains unclear. Methods Genetic variants for IR, fasting insulin, HbA1c, and fasting glucose were selected based on published genome-wide association studies, which included 188,577, 108,557, 123,665, and 133,010 individuals of European ancestry, respectively. Outcome datasets for left ventricular (LV) parameters were obtained from UK Biobank Cardiovascular Magnetic Resonance sub-study (n = 16,923). Mendelian randomization (MR) analyses with the inverse-variance weighted (IVW) method were used for the primary analyses, while weighted median, MR-Egger, and MR-PRESSO were used for sensitivity analyses. Multivariable MR analyses were also conducted to examine the independent effects of glycemic traits on LV parameters. Results In the primary IVW MR analyses, per 1-standard deviation (SD) higher IR was significantly associated with lower LV end-diastolic volume (β = − 0.31 ml, 95% confidence interval [CI] − 0.48 to − 0.14 ml; P = 4.20 × 10−4), lower LV end-systolic volume (β = − 0.34 ml, 95% CI − 0.51 to − 0.16 ml; P = 1.43 × 10−4), and higher LV mass to end-diastolic volume ratio (β = 0.50 g/ml, 95% CI 0.32 to 0.67 g/ml; P = 6.24 × 10−8) after Bonferroni adjustment. However, no associations of HbA1c and fasting glucose were observed with any LV parameters. Results from sensitivity analyses were consistent with the main findings, but with a slightly attenuated estimate. Multivariable MR analyses provided further evidence for an independent effect of IR on the adverse changes in LV parameters after controlling for HbA1c. Conclusions Our study suggests that genetic liability to IR rather than those of glycemic levels are associated with adverse changes in LV structure and function, which may strengthen our understanding of IR as a risk factor for heart failure by providing evidence of direct impact on cardiac morphology. |
| first_indexed | 2024-04-12T13:49:36Z |
| format | Article |
| id | doaj.art-8d38243a5ca748e2869b616ef6ae904c |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-12T13:49:36Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-8d38243a5ca748e2869b616ef6ae904c2022-12-22T03:30:35ZengBMCCardiovascular Diabetology1475-28402022-06-0121111210.1186/s12933-022-01540-6Effects of glycemic traits on left ventricular structure and function: a mendelian randomization studySizhi Ai0Xiaoyu Wang1Shanshan Wang2Yilin Zhao3Shuxun Guo4Guohua Li5Zhigang Chen6Fei Lin7Sheng Guo8Yan Li9Jihui Zhang10Guoan Zhao11Department of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityCenter for Sleep and Circadian Medicine, The Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical UniversityAbstract Background Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level are causally associated with cardiac structure and function remains unclear. Methods Genetic variants for IR, fasting insulin, HbA1c, and fasting glucose were selected based on published genome-wide association studies, which included 188,577, 108,557, 123,665, and 133,010 individuals of European ancestry, respectively. Outcome datasets for left ventricular (LV) parameters were obtained from UK Biobank Cardiovascular Magnetic Resonance sub-study (n = 16,923). Mendelian randomization (MR) analyses with the inverse-variance weighted (IVW) method were used for the primary analyses, while weighted median, MR-Egger, and MR-PRESSO were used for sensitivity analyses. Multivariable MR analyses were also conducted to examine the independent effects of glycemic traits on LV parameters. Results In the primary IVW MR analyses, per 1-standard deviation (SD) higher IR was significantly associated with lower LV end-diastolic volume (β = − 0.31 ml, 95% confidence interval [CI] − 0.48 to − 0.14 ml; P = 4.20 × 10−4), lower LV end-systolic volume (β = − 0.34 ml, 95% CI − 0.51 to − 0.16 ml; P = 1.43 × 10−4), and higher LV mass to end-diastolic volume ratio (β = 0.50 g/ml, 95% CI 0.32 to 0.67 g/ml; P = 6.24 × 10−8) after Bonferroni adjustment. However, no associations of HbA1c and fasting glucose were observed with any LV parameters. Results from sensitivity analyses were consistent with the main findings, but with a slightly attenuated estimate. Multivariable MR analyses provided further evidence for an independent effect of IR on the adverse changes in LV parameters after controlling for HbA1c. Conclusions Our study suggests that genetic liability to IR rather than those of glycemic levels are associated with adverse changes in LV structure and function, which may strengthen our understanding of IR as a risk factor for heart failure by providing evidence of direct impact on cardiac morphology.https://doi.org/10.1186/s12933-022-01540-6Glycemic traitsInsulin resistanceLeft ventricular structure and functionMendelian randomization |
| spellingShingle | Sizhi Ai Xiaoyu Wang Shanshan Wang Yilin Zhao Shuxun Guo Guohua Li Zhigang Chen Fei Lin Sheng Guo Yan Li Jihui Zhang Guoan Zhao Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study Cardiovascular Diabetology Glycemic traits Insulin resistance Left ventricular structure and function Mendelian randomization |
| title | Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study |
| title_full | Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study |
| title_fullStr | Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study |
| title_full_unstemmed | Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study |
| title_short | Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study |
| title_sort | effects of glycemic traits on left ventricular structure and function a mendelian randomization study |
| topic | Glycemic traits Insulin resistance Left ventricular structure and function Mendelian randomization |
| url | https://doi.org/10.1186/s12933-022-01540-6 |
| work_keys_str_mv | AT sizhiai effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT xiaoyuwang effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT shanshanwang effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT yilinzhao effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT shuxunguo effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT guohuali effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT zhigangchen effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT feilin effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT shengguo effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT yanli effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT jihuizhang effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy AT guoanzhao effectsofglycemictraitsonleftventricularstructureandfunctionamendelianrandomizationstudy |