DataSheet_1_Association Between Fat Mass or Fat Fibrotic Gene Expression and Polyneuropathy in Subjects With Obesity: A Korean Metabolic Bariatric Surgery Cohort.docx

AimWe aimed to investigate the association between obesity-related parameters and polyneuropathy (PN) and to evaluate inflammatory and fibrotic gene expression of fat as a potential mediator in subjects scheduled to undergo metabolic bariatric surgery (MBS).
MethodsThis was a cross-sectional study of MBS cohort. Body composition and visceral fat area (VFA) were quantified by bioimpedance analysis and computed tomography scan. PN was defined by Michigan Neuropathy Screening Instrument–Physical Examination score was > 2. We measured mRNA expression level of FN1, TIMP1, CCL2, and CXCL8 in omental fat tissue.
ResultsOf 189 subjects (mean age, 39.4 years; 69 [36.5%] male; mean body mass index, 38.5 kg/m2), prevalence of PN was 9.1% in subjects without diabetes (n = 110) and 20.3% in those with diabetes (n = 79). Nondiabetic subjects with PN had higher homeostatic model assessment-insulin resistance (6.8 ± 3.5 vs 4.5 ± 2.8, p = 0.041), and increased fat mass (58.5 ± 12.5 kg vs 50.5 ± 10.7 kg, p = 0.034), and VFA (309.4 ± 117.6 cm2vs 243.5 ± 94.2 cm2, p = 0.046) compared to those without PN. These obesity-related parameters were significantly associated with the presence of PN after adjusting for conventional risk factors of PN only in subjects without diabetes. In contrast, a fibrotic gene such as TIMP1 was independently associated with PN (adjusted odds ratio of 1.56; 95% confidence interval 1.06, 2.30) only in subjects with diabetes.
ConclusionIncreased adiposity was independently associated with PN in obese subjects without diabetes. In contrast, this association was not significant after adjusting conventional risk factors of PN in obese subjects with diabetes but increased fibrotic gene expression in fat was associated with PN in this group.

研究目的 本研究旨在探讨肥胖相关参数与多发性神经病（polyneuropathy, PN）之间的关联，并评估脂肪组织的炎症与纤维化基因表达，将其作为拟接受代谢减重手术（metabolic bariatric surgery, MBS）受试者的潜在中介因子。
方法 本研究为一项针对代谢减重手术队列的横断面研究。采用生物电阻抗分析（bioimpedance analysis）与计算机断层扫描（computed tomography scan）量化受试者身体成分与内脏脂肪面积（visceral fat area, VFA）。以密歇根神经病筛查工具-体格检查评分>2作为多发性神经病的诊断标准。检测网膜脂肪组织中FN1、TIMP1、CCL2及CXCL8的mRNA表达水平。
结果 本队列共纳入189名受试者，平均年龄39.4岁，其中男性69例（占比36.5%），平均体质量指数为38.5 kg/m²。无糖尿病受试者的多发性神经病患病率为9.1%（n=110），合并糖尿病受试者的患病率为20.3%（n=79）。与无多发性神经病的非糖尿病受试者相比，合并多发性神经病的非糖尿病受试者的稳态模型评估-胰岛素抵抗指数更高（6.8±3.5 vs 4.5±2.8，p=0.041），脂肪量更高（58.5±12.5 kg vs 50.5±10.7 kg，p=0.034），内脏脂肪面积也更大（309.4±117.6 cm² vs 243.5±94.2 cm²，p=0.046）。在仅校正多发性神经病常规危险因素后，上述肥胖相关参数仅在非糖尿病受试者中与多发性神经病的发生显著相关。与之相反，仅在合并糖尿病的受试者中，纤维化基因TIMP1与多发性神经病呈独立相关（校正后优势比为1.56；95%置信区间为1.06~2.30）。
结论 在无糖尿病的肥胖受试者中，体脂升高与多发性神经病呈独立相关。与之相反，在合并糖尿病的肥胖受试者中，校正多发性神经病常规危险因素后，上述关联不再显著，但脂肪组织的纤维化基因表达升高与该人群的多发性神经病相关。