Tier 4 — mechanistic

Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes

Xie W, Wood AR, Lyssenko V, Weedon MN, Knowles JW, Alkayyali S, Assimes TL, Quertermous T, Abbasi F, Paananen J, Häring H, Hansen T, Pedersen O, Smith U, Laakso M, MAGIC Investigators, DIAGRAM Consortium, GENESIS Consortium, RISC Consortium, Dekker JM, Nolan JJ, Groop L, Ferrannini E, Adam KP, Gall WE, Frayling TM, Walker M
Diabetes 2013 62(6):2141-2150

Bibliography

PubMed
PMID 23378610
PubMed Central
PMC3661655
DOI
10.2337/db12-0876
Funding
Support included Wellcome Trust, Medical Research Council, EU research programs, American Heart Association and AstraZeneca involvement in RISC.
Competing interests
One author was employed by the metabolomics company Metabolon; the RISC study also reported AstraZeneca support.

Study snapshot

DesignHuman genetic association and Mendelian-randomization analyses
ModelAdult humans
Sample1,004 RISC participants; replication in 342 Botnia participants, with larger trait consortia
InterventionGWAS of insulin-sensitivity-related metabolites and assessment of associated variants
DurationGenetic epidemiology; no dosing period
EndpointsGlycine-related variants; Insulin sensitivity; Type 2 diabetes

What the study showed, in plain terms

This genetic study identified determinants of glycine-related metabolites but did not find consistent evidence that the variants caused insulin resistance or diabetes.

Key findings

  • Several metabolite and metabolite-ratio associations were identified.
  • The authors found no robust association of the glycine-pathway variants with diabetes-related traits.

What this study can and cannot tell us

Genetic instruments may capture only part of glycine biology.

This is neither a supplementation trial nor proof that low measured glycine causes diabetes.

Related papers in the corpus

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The metabolic response to ingested glycine
Gannon MC et al. · The American journal of clinical nutrition · 2002
Tier 2
Effect of glycine on insulin secretion and action in healthy first-degree relatives of type 2 diabetes mellitus patients
González-Ortiz M et al. · Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2001
Tier 2
Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes
Cruz M et al. · Journal of endocrinological investigation · 2008
Tier 2
Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure
Díaz-Flores M et al. · Canadian journal of physiology and pharmacology · 2013
Tier 4
Metabolic impact of dietary glycine supplementation in individuals with severe obesity
Tan HC et al. · Scientific reports · 2025
Tier 4
De Novo Glycine Synthesis Is Reduced in Adults With Morbid Obesity and Increases Following Bariatric Surgery
Tan HC et al. · Frontiers in endocrinology · 2022

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction