Tier 4 — mechanistic

Association of Betaine, Choline, and TMAO with Type 2 Diabetes in Rural China: A Nested Case-Control Study from the Handan Eye Study (HES)

Jun Liang, Jie Hao, Yu Qin, Ou Liu, Kunning Shao, Wei Zhao, Jiangping Wen
Diabetes, metabolic syndrome and obesity : targets and therapy 2025 18:2537-2545

Bibliography

PubMed
PMID 40740408
PubMed Central
PMC12309563
DOI
10.2147/DMSO.S522576
Funding
Funding was not specified in the indexed record or accessible funding metadata.
Competing interests
Reported disclosure: The authors report no conflicts of interest in this work.

Study snapshot

DesignNested case-control study
ModelHuman participants
Sample209 incident diabetes cases and 394 controls
InterventionMeasured betaine status and related metabolites; no randomized TMG treatment
Duration6.5 years
EndpointsDiabetes incidence; Insulin resistance

What the study showed, in plain terms

Published in 2025, this source examined human observational and biomarker research. Design: Nested case-control study. Sample/model: 209 incident diabetes cases and 394 controls. The exposure or intervention was Measured betaine status and related metabolites; no randomized TMG treatment. Follow-up or treatment period: 6.5 years.

Betaine was lower in future diabetes cases, but the adjusted diabetes association was not significant; inverse insulin-resistance correlations remained.

Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome. Diet recall, case selection or illness-related metabolite changes may introduce bias.

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Key findings

  • Betaine was lower in future diabetes cases, but the adjusted diabetes association was not significant; inverse insulin-resistance correlations remained.
  • The recorded outcome domains were Diabetes incidence; Insulin resistance.
  • The exposure was observed rather than assigned as an isolated supplement treatment.

What this study can and cannot tell us

  • Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome. Diet recall, case selection or illness-related metabolite changes may introduce bias.
  • Confounding, dietary patterns, illness, medication use and reverse causation can influence an association. Blood or dietary concentrations do not identify the effect of starting a capsule.
  • Source basis: Accessible full-text extract plus indexed bibliographic data. Missing method details, funding information or participant denominators are not inferred.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology