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Byung-Wan Lee 1 Article
Causal effect of fasting serum glucose on atherosclerotic cardiovascular disease: a multivariable Mendelian randomization
Su Hyun Lee, Heejin Kimm, Byung-Wan Lee, Chung Mo Nam, So Young Kim, Sunmi Lee, Sun Ha Jee
Epidemiol Health. 2024;46:e2024096.   Published online December 6, 2024
DOI: https://doi.org/10.4178/epih.e2024096
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AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Observational studies have reported that diabetes is a risk factor that increases the risk of atherosclerotic cardiovascular disease (ASCVD). However, the causal relationship remains a matter of debate. This study aimed to analyze the relationship between fasting serum glucose (FSG) and ASCVD.
METHODS
This study used data from the Korean Cancer Prevention Study-II (KCPS-II) Biobank, consisting of 159,844 people recruited with consent from 18 health examination centers from 2004 to 2013. Outcomes were confirmed based on diagnoses on hospital discharge summaries from National Health Insurance System. We used linear and non-linear Mendelian randomization (MR) methods. The outcome data were obtained from KCPS-II, and the exposure data were derived from the Korean Genome Epidemiology Study.
RESULTS
First, a prospective cohort study estimated that for each 10 mg/dL increase in FSG level, the risk of ASCVD increased by 4% (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03 to 1.05). Second, the 2-sample MR study showed that every 10 mg/dL increase in FSG influenced the risk of ASCVD (odds ratio [OR], 1.11; 95% CI, 1.04 to 1.18). Third, the multivariable MR study showed that the OR per 10 mg/dL increase in FSG on ASCVD was 1.14 (p<0.001). Similar results were found for a 10 mg/dL increase in FSG and ischemic heart disease (IHD), but a significant relationship with stroke was not found. When performing non-linear MR, a linear relationship was observed between fasting blood sugar and ASCVD, including IHD and stroke.
CONCLUSIONS
FSG showed a linear and causal association with IHD, but not with stroke.
Summary
Korean summary
그동안 당뇨병이 심뇌혈관질환 발생에 위험요인이라는 역학적인 관찰연구는 많이 발표되었지만, 이러한 관련성에 대한 인과적 관련성에 대부분 연구는 서양인을 대상으로 발표되었고, 한국인 자료를 통해 발표된 적은 없었다. 이 연구는 관찰연구의 제한점으로 부각되는 혼란변수와 측정오류에 덜 영향을 받는 새로운 방법론으로써 다변수 멘델리언 무작위화 방법을 사용하여 공복혈당과 심뇌혈관질환의 인과성을 분석하였다. 분석결과, 공복혈당은 허혈성 심질환 발생위험에 인과적인을 관련성을 보였고 뇌졸중에 대해서는 인과적이지 않았다.
Key Message
Over the years, numerous epidemiological observational studies have reported that diabetes is a risk factor for cardiovascular and cerebrovascular diseases. However, most of these studies examining this association were conducted on Western populations, and no studies have been published using Korean data. This study employed a new methodology—multivariable Mendelian randomization—which is less affected by confounding factors and measurement errors, often highlighted as limitations of observational studies, to analyze the causal relationship between fasting glucose levels and cardiovascular and cerebrovascular diseases. The analysis revealed a causal relationship between fasting glucose levels and the risk of ischemic heart disease, while no causal association was observed with stroke.

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