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Blood lipid profile, HbA1c, fasting glucose, and diabetes: a cohort study and a two-sample Mendelian randomization analysis

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Abstract

Purpose

The prevalence of diabetes is increasing worldwide. The associations between the lipid profile and glycated hemoglobin (HbA1c), fasting glucose, and diabetes remain unclear, so we aimed to perform a cohort study and a two-sample Mendelian randomization (MR) study to investigate the causality between blood lipid profile and HbA1c, fasting glucose, and diabetes.

Methods

A total of 25,171 participants from the Taiwan Biobank were enrolled. We applied a cohort study and an MR study to assess the association between blood lipid profile and HbA1c, fasting glucose, and diabetes. The summary statistics were obtained from the Asian Genetic Epidemiology Network (AGEN), and the estimates between the instrumental variables (IVs) and outcomes were calculated using the inverse-variance weighted (IVW) method. A series of sensitivity analyses were performed.

Results

In the cohort study, high-density lipoprotein cholesterol (HDL-C) was negatively associated with HbA1c, fasting glucose, and diabetes, while the causal associations between HDL-C and HbA1c (βIVW = − 0.098, p = 0.003) and diabetes (βIVW = − 0.594, p < 0.001) were also observed. Furthermore, there was no pleiotropy effect in this study using the MR-Egger intercept test and MR-PRESSO global test.

Conclusions

Our results support the hypothesis that a genetically determined increase in HDL-C is causally related to a reduction in HbA1c and a lower risk of diabetes.

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Data availability

Summary data of blood lipid profiles GWAS were used in our study is available at the AGEN consortium website (https://blog.nus.edu.sg/agen/summary-statistics/lipids/).

Abbreviations

MR:

Mendelian randomization

IVW:

Inverse-variance weighted

HbA1c:

Glycated hemoglobin

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

RCTs:

Randomized controlled trials

IVs:

Instrumental variables

SNPs:

Single nucleotide polymorphisms

WHR:

Waist-hip ratio

BMI:

Body mass index

PRESSO:

Pleiotropy residual sum and outliers

MBE:

Mode-based estimate

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Funding

This work was supported by grants from the Ministry of Science and Technology, Taiwan [MOST 107-2314-B-037-086-MY3 and MOST 110-2314-B-037-048 MY3]. The funding agencies had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

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Authors and Affiliations

  1. Department of Public Health, College of Health Science, Kaohsiung Medical University, No. 100, Shi-Chuan 1st Rd, Kaohsiung, 807, Taiwan

    Y.-C. Lin & T.-N. Wang

  2. Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    H.-P. Tu

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Contributions

YCL and TNW contributed to the conception and design. TNW contributed to the acquisition of data. YCL and HPT contributed to statistical analysis and interpretation. YCL and TNW drafted the manuscript for important intellectual content. TNW is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to T.-N. Wang.

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The authors have declared that they have no conflict of interest.

Ethical approval

Ethical approval for the study was granted by the Institutional Review Board of Kaohsiung Medical University and Chung-Ho Memorial Hospital and the Ethics and Governance Committee (EGC) of the Taiwan Biobank.

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Written informed consent of participation was obtained from all participants when joining TWB and the personal information of each participant was fully encrypted for protection.

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Lin, YC., Tu, HP. & Wang, TN. Blood lipid profile, HbA1c, fasting glucose, and diabetes: a cohort study and a two-sample Mendelian randomization analysis. J Endocrinol Invest 47, 913–925 (2024). https://doi.org/10.1007/s40618-023-02209-x

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