AUTHOR=Guo Nuojin , Shi Hekai , Zhao Hongmei , Abuduani Yierfan , Chen Da , Chen Xishuang , Wang Hua , Li Peicheng TITLE=Causal relationships of lifestyle behaviours and body fat distribution on diabetic microvascular complications: a Mendelian randomization study JOURNAL=Frontiers in Genetics VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1381322 DOI=10.3389/fgene.2024.1381322 ISSN=1664-8021 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.