Guo Nuojin, Shi Hekai, Zhao Hongmei, Abuduani Yierfan, Chen Da, Chen Xishuang, Wang Hua, Li Peicheng
Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Bariatric and Metabolic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai, China.
Front Genet. 2024 Jul 8;15:1381322. doi: 10.3389/fgene.2024.1381322. eCollection 2024.
To determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR).
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.
There was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04-1.30; = 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; < 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15-1.40; < 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95-3.45; < 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications.
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.
通过孟德尔随机化（MR）确定生活方式行为和体脂分布与糖尿病微血管并发症之间的因果关系。
从英国生物银行（UKB）和芬兰基因库中提取与生活方式行为、腹型肥胖、全身性肥胖和糖尿病微血管并发症显著相关的基因变异。逆方差加权（IVW）法被视为主要方法。主要结果以每标准差（SD）增加的比值比（OR）表示，并进行了一系列敏感性分析以验证结果的稳定性。
吸烟与糖尿病视网膜病变的发生存在正因果关系（OR = 1.16；95%CI：1.04 - 1.30；P = 0.01）。所有代表腹型肥胖的指标与糖尿病微血管并发症均存在统计学显著的因果关联。关于全身性肥胖，体重指数（BMI）与糖尿病肾病（OR = 1.92；95%CI：1.58 - 2.33；P < 0.001）、糖尿病视网膜病变（OR = 1.27；95%CI：1.15 - 1.40；P < 0.001）和糖尿病神经病变（OR = 2.60；95%CI：1.95 - 3.45；P < 0.001）存在显著因果关联。其他指标，包括（左侧）腿部脂肪量和（左侧）手臂脂肪量与糖尿病微血管并发症也存在显著正因果关系。
我们的研究结果表明，吸烟与糖尿病视网膜病变的发生存在基因因果关联，而非糖尿病肾病和糖尿病神经病变。此外，腹型肥胖和全身性肥胖均为糖尿病微血管并发症的危险因素。需要注意的是，以腰围（WC）表示的腹型肥胖是最显著的危险因素。
