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Observational Study
. 2025 May 16;15(1):20.
doi: 10.1038/s41387-025-00370-1.

Association between Apolipoprotein B and diabetic nephropathy: insights from the National Health and Nutrition Examination Survey 2007-2016 and Mendelian randomization analysis

Hui Wang  1 , Sensen Wu  1 , Dikang Pan  1 , Yachan Ning  1 , Yanhong Fu  2 , Chunjing Feng  3 , Jianming Guo  4 , Zichuan Liu  5 , Yongquan Gu  6
Affiliations
Observational Study

Association between Apolipoprotein B and diabetic nephropathy: insights from the National Health and Nutrition Examination Survey 2007-2016 and Mendelian randomization analysis

Hui Wang et al. Nutr Diabetes. .

Abstract

Background: This study aimed to investigate the role of Apolipoprotein B (Apo B) in diabetic nephropathy (DN) from epidemiological and genetic perspectives.

Methods: We employed weighted multivariable-adjusted logistic regression to assess the relationship between ApoB and DN risk, utilizing data from the National Health and Nutrition Examination Survey spanning 2007-2016. Then, we used restricted cubic splines (RCS) to flexibly model and visualize the relation of predicted ApoB levels with DN risk. Subsequently, a bidirectional two-sample Mendelian randomization study using genome-wide association study summary statistics was performed. The primary Inverse Variance Weighted method, along with supplementary MR approaches, was employed to verify the causal link between ApoB and DN. Sensitivity analyses were conducted to confirm the robustness of the results.

Results: Our observational study enrolled 2242 participants with diabetes mellitus from NHANES. The multivariable logistic regression model indicated that elevated ApoB levels (>1.2 g/L), compared to low levels (<0.8 g/L), were significantly associated with DN risk (P < 0.05). The RCS model revealed a positive linear association with the risk of DN when ApoB levels exceeded 1.12 g/L (OR = 1.29, 95% CI: 1.07-1.57, P = 0.008). However, the MR IVW method did not reveal a direct causal effect of DN on ApoB (OR: 0.976; 95% CI: 0.950-1.004; P = 0.095), nor a direct causal effect of ApoB on DN (OR: 0.837; 95% CI: 0.950-1.078; P = 0.428).

Conclusion: The evidence from observational studies indicates a positive correlation between ApoB levels exceeding 1.12 g/L and the onset of DN. However, the causal effects of ApoB on DN and vice versa were not supported by the MR analysis.

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Conflict of interest statement

Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics approval and consent to participate: Due to the openly accessible nature of the NHANES data, an ethical review was deemed unnecessary. Written informed consent was obtained from all participants involved in the study.

Figures

Fig. 1
Fig. 1. Association between ApoB and DN with the restricted cubic spline function.
Model with 4 knots located at 5th, 35th, 65th, and 90th percentiles. The Y-axis represents the OR to present DN for any value of ApoB compared to individuals with 1.2 g/L of ApoB. DN = Diabetic nephropathy, ApoB = Apolipoprotein B.
Fig. 2
Fig. 2. Forest plot of MR analysis, the association of ApoB with the risk of DN.
DN diabetic nephropathy, ApoB Apolipoprotein B.
Fig. 3
Fig. 3. Scatter plots of primary MR analysis.
The slope of each line corresponds to the estimated MR effect in different models. A ApoB on DN, (B) DN on ApoB. DN diabetic nephropathy, ApoB Apolipoprotein B.
Fig. 4
Fig. 4. Forest plot of MR analysis, the association of DN with ApoB.
DN diabetic nephropathy, ApoB Apolipoprotein B.
See this image and copyright information in PMC

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