Higher serum MCFAs may reduce diabetes risk

Dietary medium-chain fatty acids (MCFAs) are inversely associated with the risk of developing type 2 diabetes mellitus (T2DM), reports a study, noting a possible interaction between genetic susceptibility and circulating octanoic acid in moderating diabetes risk.

"Our study revealed a statistically significant association between higher circulating levels of octanoic acid and nonanoic acid and reduced risks of T2DM in a nested case-control study,” the researchers said. “Furthermore, lifestyle factors and genetic predisposition influenced the association between MCFAs and diabetes risk.”

Baseline serum MCFAs (n=5) in a nested case-control study, which involved 1,701 diabetes patients and 1,707 matched normoglycaemic control individuals from the China Cardiometabolic Disease and Cancer Cohort Study, were examined.

The research team explored the associations between MCFAs and T2DM, both overall and stratified by diabetes genetic susceptibility. They also calculated the genetic risk scores (GRS) based on 82 T2DM-related genetic variants.

The fully adjusted conditional logistic regression model showed the inverse dose-response association of serum octanoic acid (odds ratio [OR], 0.90, 95 percent confidence interval [CI], 0.82–0.98) and nonanoic acid (OR, 0.84, 95 percent CI, 0.74–0.95) with diabetes risk. [J Clin Endoc Metab 2025;110:441-451]

In subgroup analysis, the inverse associations between MCFAs and incident diabetes were stronger among individuals with no physical activity (octanoic acid: p_interaction=0.042; nonanoic acid: p_interaction=0.034; decanoic acid: p_interaction=0.037). The inverse relationship between octanoic acid and diabetes risk was also notably increased among those with high vs low genetic risk.

In addition, there were statistically significant interactions seen between octanoic acid and GRS on the risk of T2DM (p_interaction=0.003).

“These results offer valuable insights for the implementation of precision nutrition both in clinical and public health settings,” the researchers said. “Our findings generally support the protective effect of MCFAs but also emphasize the personalized approaches in improving serum MCFA profiles for T2DM prevention, which could be tailored according to individuals’ genetic and lifestyle profiles.”

Mechanism

The decrease in T2DM risks associated with higher serum MCFAs could be explained by certain potential mechanisms. For instance, an earlier study investigating the intake of octanoic, decanoic, and lauric acids found enhanced glucose metabolism as well as reversal of insulin resistance, particularly in the skeletal muscle. [Diabetes 2020;70:91‐98]

“It is worth mentioning that lifestyle behaviours may inevitably influence the association between fatty acid levels and diabetes risk,” the researchers said. “Our findings demonstrate that individuals with poor lifestyle patterns, particularly those who are physically inactive, exhibit stronger inverse associations between serum MCFAs and incident T2DM risks.”

A previous study suggested that dietary fatty acids could serve as “compensatory factors” to counteract the adverse effects of traditional nonideal lifestyles. Thus, supplementation with specific octanoic and nonanoic acids could be beneficial to individuals with unhealthy lifestyle behaviours. [J Nutr Biochem 2016;36:1‐20]

“Future research using full cohort-level data is needed to more rigorously evaluate the association and underlying mechanisms linking MCFA metabolism and genetic predisposition,” the researchers said.