Causality between sarcopenia and diabetic nephropathy: a bidirectional Mendelian randomization study

Linan Ren; Yao Wang; Feng Ju; Meixin Sun; Xiaokun Gang; Guixia Wang

doi:10.3389/fendo.2023.1188972

Causality between sarcopenia and diabetic nephropathy: a bidirectional Mendelian randomization study

Front Endocrinol (Lausanne). 2023 May 22:14:1188972. doi: 10.3389/fendo.2023.1188972. eCollection 2023.

Authors

Linan Ren¹, Yao Wang², Feng Ju³, Meixin Sun¹, Xiaokun Gang¹, Guixia Wang¹

Affiliations

¹ Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, China.
² Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, China.
³ Department of Orthopedics, Yuci District People's Hospital, Yuci, Shanxi, China.

Abstract

Background and purpose: Observational studies have shown that sarcopenia and diabetic nephropathy (DN), are closely related; however, the causal relationship is unclear. This study aims to address this issue using a bidirectional Mendelian randomization (MR) study.

Methodology: We data from genome-wide association studies including appendicular lean mass (n = 244,730), grip strength (right: n = 461,089, left: n = 461026), walking speed (n = 459,915), and DN (3283 cases and 181,704 controls) to conduct a bidirectional MR study. First, we conducted a Forward MR analysis to evaluate the causality of sarcopenia on the risk of DN from the genetic perspective with appendicular lean mass, grip strength, and walking speed as exposure and DN as the outcome. Then, DN as the exposure, we performed a Reverse MR analysis to determine whether DN impacted the appendicular lean mass, grip strength, and walking speed of the appendices. Finally, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and Leave-one-out analyses, were conducted to assess the MR analysis's accuracy further.

Results: According to a forward MR analysis, a genetically predicted decrease in appendicular lean mass is associated with an increased risk of developing DN risk (inverse variance weighting[IVW]: odd ratio [OR] = 0.863, 95% confidence interval [CI] 0.767-0.971; P = 0.014). According to reverse MR results, grip strength decreased as DN progressed (IVW: right β = 0.003, 95% CI: - 0.021 to - 0.009, P = 5.116e-06; left β = 0.003, 95% CI: - 0.024 to - 0.012, P = 7.035e-09). However, the results of the other MR analyses were not statistically different.

Conclusion: Notably, our findings suggest that the causal relationship between sarcopenia and DN cannot be generalized. According to analysis of the individual characteristic factors of sarcopenia, reducing in appendicular lean mass increases the risk of developing DN and DN is linked to reduced grip strength. But overall, there is no causal relationship between sarcopenia and DN, because the diagnosis of sarcopenia cannot be determined by one of these factors alone.

Keywords: appendicular lean mass; causality; diabetic nephropathy; grip strength; walking speed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus*
Diabetic Nephropathies* / genetics
Genome-Wide Association Study
Hand Strength
Humans
Mendelian Randomization Analysis
Sarcopenia* / complications
Sarcopenia* / diagnosis
Sarcopenia* / genetics

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81972372), the National Natural Science Foundation of China (82272993), the Bethune Fund (G2017044), and the Department of Science and Technology of Jilin Province (20190201034JC, 20190303152SF).