Causal relationships of lifestyle behaviours and body fat distribution on diabetic microvascular complications: a Mendelian randomization study

Nuojin Guo; Hekai Shi; Hongmei Zhao; Yierfan Abuduani; Da Chen; Xishuang Chen; Hua Wang; Peicheng Li

doi:10.3389/fgene.2024.1381322

Causal relationships of lifestyle behaviours and body fat distribution on diabetic microvascular complications: a Mendelian randomization study

Front Genet. 2024 Jul 8:15:1381322. doi: 10.3389/fgene.2024.1381322. eCollection 2024.

Authors

Nuojin Guo^#¹, Hekai Shi^#², Hongmei Zhao¹, Yierfan Abuduani¹, Da Chen¹, Xishuang Chen¹, Hua Wang¹, Peicheng Li¹

Affiliations

¹ Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
² Department of Bariatric and Metabolic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai, China.

^# Contributed equally.

Abstract

Objectives: To determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR).

Methods: Genetic variants significantly associated with lifestyle behaviours, abdominal obesity, generalized obesity and diabetic microvascular complications were extracted from the UK Biobank (UKB) and FinnGen. The inverse variance weighted (IVW) method was regarded as the primary method. The main results were presented in odds ratio (OR) per standard deviation (SD) increase, and a series of sensitivity analyses were also conducted to validate the stability of the results.

Results: There was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04-1.30; p = 0.01). All of the indicators representing abdominal obesity had a statistically significant causal association with diabetic microvascular complications. Concerning generalized obesity, there were significant causal associations of body mass index (BMI) on diabetic nephropathy (OR = 1.92; 95%CI: 1.58-2.33; p < 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15-1.40; p < 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95-3.45; p < 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications.

Conclusion: Our findings suggested that smoking has a genetically causal association with the development of diabetic retinopathy rather than diabetic nephropathy and diabetic neuropathy. In addition, both abdominal obesity and generalized obesity are risk factors for diabetic microvascular complications. To note, abdominal obesity represented by waist circumference (WC) is the most significant risk factor.

Keywords: Mendelian randomization study; body fat distribution; causality; diabetic microvascular complications; lifestyle behaviours.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This article was supported by Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai. The Discipline Leader Program of Pudong New District Health and Family Planning Commission (Grant PWRd 2018-02). The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.