Guo Mengxiao, Mao Yuejian, Xie Feng, Wang Ruirui, Zhang Lei
Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
Endocrinology Department, Wuxi Rehabilitation Hospital, Wuxi, 214000, People's Republic of China.
Diabetes Metab Syndr Obes. 2025 Apr 29;18:1353-1364. doi: 10.2147/DMSO.S495623. eCollection 2025.
The distribution of body fat plays a critical role in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the specific metabolic profiles and biomarkers that distinguish the different obesity phenotypes in T2DM remain to be fully elucidated. Bile acids (BAs), which are recognized as pivotal signaling molecules in the regulation of glucose and lipid metabolism, warrant further investigation to characterize their profiles across different obesity phenotypes. Understanding the clinical significance of these BAs in the management of T2DM is essential and merits thorough exploration.
In this cross-sectional study conducted at the Zhangjiang Community Health Service Center in Shanghai, ninety-nine elderly participants were recruited and categorized into four groups: non-diabetic controls (NC), T2DM with lean phenotype (TN), T2DM with overweight phenotype (TO), and T2DM with abdominal obesity phenotype (TA). Biochemical indices, visceral adiposity indices, and bile acid (BA) profiles were analyzed and compared across the groups.
Healthy individuals exhibited lower triglyceride levels, waist-to-hip ratio (WHR), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI), as well as higher HDL-c level and total BA levels compared to T2DM patients. T2DM patients with different obesity phenotypes displayed distinct BA profiles. Specifically, the TN group showed higher levels of conjugated DCA BA species, GDCA, and TDCA, compared to the TO group. These BA species are essential for regulating lipid and glucose metabolism. In contrast, the TA group exhibited higher ratios of 12α-hydroxylated BAs to non 12α-hydroxylated BAs, taurine-conjugated BAs to glycine-conjugated BAs, and higher levels of LCA compared to the TO group. Additionally, CVAI was positively associated with unconjugated SBAs, CA-7S, and DLCA.
These results revealed that T2DM patients with different obesity phenotypes exhibit distinct BA profiles. Specific BAs, particularly GDCA, TDCA, and LCA, are closely associated with adiposity indices and may serve as crucial signaling molecules in modulating visceral adiposity, serum lipid profiles, and glucose homeostasis in obese T2DM patients. These BA species play a pivotal role in the pathogenetic process underlying diabetes and various forms of obesity. Furthermore, their significance highlights their potential contributors to drug development and as therapeutic targets for T2DM patients with specific obesity subtypes.
体脂分布在2型糖尿病(T2DM)发病机制中起关键作用。然而,区分T2DM中不同肥胖表型的具体代谢特征和生物标志物仍有待充分阐明。胆汁酸(BAs)被认为是调节葡萄糖和脂质代谢的关键信号分子,值得进一步研究以明确其在不同肥胖表型中的特征。了解这些胆汁酸在T2DM管理中的临床意义至关重要,值得深入探讨。
在上海张江社区卫生服务中心进行的这项横断面研究中,招募了99名老年参与者,并将其分为四组:非糖尿病对照组(NC)、瘦型T2DM(TN)、超重型T2DM(TO)和腹型肥胖型T2DM(TA)。对各组的生化指标、内脏脂肪指数和胆汁酸(BA)谱进行分析和比较。
与T2DM患者相比,健康个体的甘油三酯水平、腰臀比(WHR)、内脏脂肪指数(VAI)和中国内脏脂肪指数(CVAI)较低,高密度脂蛋白胆固醇(HDL-c)水平和总胆汁酸水平较高。不同肥胖表型的T2DM患者表现出不同的胆汁酸谱。具体而言,与TO组相比,TN组的结合型DCA胆汁酸种类、甘氨胆酸(GDCA)和牛磺胆酸(TDCA)水平较高。这些胆汁酸种类对调节脂质和葡萄糖代谢至关重要。相反,与TO组相比,TA组的12α-羟基化胆汁酸与非12α-羟基化胆汁酸的比例、牛磺酸结合型胆汁酸与甘氨酸结合型胆汁酸的比例更高,且石胆酸(LCA)水平更高。此外,CVAI与未结合型次级胆汁酸、鹅脱氧胆酸-7硫酸酯(CA-7S)和二羟基石胆酸(DLCA)呈正相关。
这些结果表明,不同肥胖表型的T2DM患者表现出不同的胆汁酸谱。特定的胆汁酸,特别是GDCA、TDCA和LCA,与肥胖指数密切相关,可能是调节肥胖T2DM患者内脏脂肪、血脂谱和葡萄糖稳态的关键信号分子。这些胆汁酸种类在糖尿病和各种形式肥胖的发病过程中起关键作用。此外,它们的重要性突出了其在药物开发中的潜在作用以及作为特定肥胖亚型T2DM患者治疗靶点的潜力。