Mengxiao Guo,1,2 Yuejian Mao,3 Feng Xie,4 Ruirui Wang,1,5,* Lei Zhang1,5,* 

1Shanghai 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; 2Endocrinology Department, Wuxi Rehabilitation Hospital, Wuxi, 214000, People’s Republic of China; 3Mengniu Institute of Nutrition Science, Inner Mongolia Mengniu Dairy Co. LTD, Hohhot, 010000, People’s Republic of China; 4Traditional Chinese Medicine Department, Beicai Community Health Service Center of Pudong New District, Shanghai, 200000, People’s Republic of China; 5State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lei Zhang, Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Zhangjiang Gaoke, Pudong New Area, Shanghai, People’s Republic of China, Email zhanglei37@sina.com Ruirui Wang, Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Zhangjiang Gaoke, Pudong New Area, Shanghai, People’s Republic of China, Email wangruirui@shutcm.edu.com

Objective: 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.
Design: 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.
Results: 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.
Conclusion: 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.

Keywords: bile acids and salts, diabetes mellitus, obesity