Liang Jun, Hao Jie, Qin Yu, Liu Ou, Shao Kunning, Zhao Wei, Wen Jiangping
Department of Laboratory, The First Hospital of Tsinghua University, Beijing, People's Republic of China.
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, People's Republic of China.
Diabetes Metab Syndr Obes. 2025 Jul 26;18:2537-2545. doi: 10.2147/DMSO.S522576. eCollection 2025.
Conflicting evidence exists regarding the association of gut microbiota-related metabolites - TMAO and its precursor choline and betaine with type 2 diabetes Mellitus (T2DM), particularly in rural Chinese populations. This study aimed to prospectively examine these relationships in a northern rural Chinese cohort.
A nested case-control study was conducted within the Handan Eye Study. At baseline (2006-2007), 5,512 participants aged ≥30 years were enrolled. After 6.5 years of follow-up, 209 incident T2DM cases and 394 age- and sex-matched controls were included. Plasma choline, betaine, and TMAO levels were measured using ultra-performance liquid chromatography. Logistic regression and linear models assessed associations with T2DM risk, insulin resistance (IR), and metabolic parameters.
Baseline betaine level was lower in the T2DM group compared to controls (betaine: 7431.4 ng/mL versus 7821.5 ng/mL). After adjusting for BMI, waist-to-hip ratio, and diabetes history, no significant associations were found between choline, betaine, or TMAO and T2DM risk. However, higher betaine quartiles showed a trend toward reduced T2DM risk (Q4 vs Q1 OR: 0.59, 95% CI: 0.34-1.06). Betaine was inversely correlated with HOMA-IR (β = -0.16), HOMA-β (β = -0.13), and TyG index (β = -0.21) (p < 0.05). Plasma choline levels were positively associated with fruit intake frequency, while TMAO levels decreased with higher exercise intensity.
Betaine may play a protective role against dyslipidemia, adiposity, and T2DM risk in rural Chinese populations. Further studies are needed to explore TMAO's complex role in diabetes development.
关于肠道微生物群相关代谢物——氧化三甲胺（TMAO）及其前体胆碱和甜菜碱与2型糖尿病（T2DM）之间的关联，存在相互矛盾的证据，尤其是在中国农村人群中。本研究旨在对中国北方农村队列中的这些关系进行前瞻性研究。
在邯郸眼病研究中进行了一项巢式病例对照研究。在基线期（2006 - 2007年），纳入了5512名年龄≥30岁的参与者。经过6.5年的随访，纳入了209例新发T2DM病例和394例年龄及性别匹配的对照。使用超高效液相色谱法测量血浆胆碱、甜菜碱和TMAO水平。逻辑回归和线性模型评估了与T2DM风险、胰岛素抵抗（IR）和代谢参数的关联。
T2DM组的基线甜菜碱水平低于对照组（甜菜碱：7431.4 ng/mL对7821.5 ng/mL）。在调整体重指数、腰臀比和糖尿病史后，未发现胆碱、甜菜碱或TMAO与T2DM风险之间存在显著关联。然而，较高的甜菜碱四分位数显示出T2DM风险降低的趋势（Q4 vs Q1 OR：0.59，95%CI：0.34 - 1.06）。甜菜碱与HOMA - IR（β = -0.16）、HOMA - β（β = -0.13）和TyG指数（β = -0.21）呈负相关（p < 0.05）。血浆胆碱水平与水果摄入频率呈正相关，而TMAO水平随运动强度增加而降低。
甜菜碱可能对中国农村人群的血脂异常、肥胖和T2DM风险起到保护作用。需要进一步研究来探索TMAO在糖尿病发生发展中的复杂作用。
