Evaluating the association between Mediterranean Diet adherence and type 2 diabetes using nutritional biomarkers

In a recent study published in PLOS Medicine, researchers developed a novel method for objective assessment of the effect Mediterranean Diet on type II diabetes (T2D), which used composite nutritional biomarkers.

Study: A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study. Image Credit: AntoninaVlasova/Shutterstock.com


The Mediterranean dietary pattern emphasizes consuming more fruits, vegetables, fish, seafood, nuts, whole grains and a modest consumption of wine, meat, and dairy products.

Observational research evidenced that it helps prevent T2D; however, mainly through self-reported dietary assessment, with modest effect sizes.

Since studies on this topic have almost exclusively used self-reported tools, high-quality evidence on the effect of Mediterranean dietary patterns on T2D risk is lacking.

About the study

In the present study, researchers first derived a composite nutritional biomarker score that could discriminate (objectively) between the Mediterranean Diet and the habitual diet arms of a randomized clinical trial (RCT), the MedLey trial. The biomarker score comprised a linear aggregation of a total of 23 biomarkers.

This trial tested the effects of the Mediterranean Diet on cardiovascular risk factors and cognitive function among healthy adults aged ≥65 years in Adelaide, Australia. In this, the researchers measured circulating carotenoids and fatty acids as a composite biomarker of Mediterranean diet compliance.

The researchers used high-performance liquid chromatography (HPLC)  to assay carotenoids, and they used erythrocyte membranes to assay individual fatty acids. The final analytical sample of this RCT encompassed 67 and 61 participants in the Mediterranean Diet and the habitual diet groups, respectively.

Next, the team applied the derived biomarker score with incident T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct population-based observational cohort study, assessed via self-reported tools.

In this way, the researchers demonstrated that combining data from an RCT and an observational study could strengthen the evidence for using biomarkers in research on dietary patterns.

Additionally, they estimated the potential population impact of greater adherence to the Mediterranean diet and the future risk of T2D.


The current study had 22,202 participants, of which 9,453 developed incident T2D. The team followed up with 13,313 subcohort participants over a median of 9.7 years. The use of objective composite biomarkers fetched stronger inverse correlations (three-fold higher) than for the Mediterranean diet assessed via subjective tools and at a markedly greater magnitude.

In addition, this approach alleviated the restrictions imposed by small effect sizes in nutritional epidemiological studies.

The study model assessed that a 10-percentile higher score of the objectively assessed Mediterranean dietary pattern, i.e., stricter adherence to this diet, could avert 11% of new T2D cases, assuming a causal relationship. However, the current study could not confirm the same.

The inverse correlations of the biomarker score with T2D were independent of measured adiposity, and BMI exerted no effect modification. In the comparative analysis, this effect size was ~40% of the estimated effect of declining mean body mass index (BMI).

Thus, stricter adherence to the Mediterranean dietary pattern could considerably decrease the T2D incidence even without modifying body weight and across the population with varying adiposity levels.

Strikingly, the 95% prediction interval for the observed inverse association did not encompass the null, indicating the feasibility of extending this finding to comparable populations.

The authors compared the findings with two previous studies using biomarker scores comprised of nutritional biomarkers. One used a hypothesis-free approach prone to confounding by non-dietary regulation of nutritional biomarkers.

The second one used a novel feeding design and performed a data-driven variable selection from a suite of nutritional biomarkers than the current study.

This comparison further reinstated the usefulness of the combination of carotenoids and fatty acids for objective assessment and evaluation of nutritional biomarker groups in a data-driven manner. For example, polyphenol biomarkers are promising, but there is limited evidence of their usefulness for multivariate modeling.


Overall, the current study findings aligned well with interventional evidence from a Mediterranean population and could be used to develop personalized dietary guidelines, even public health policy.

Adopting a Mediterranean diet could help prevent T2D in Western European adults more than previously estimated from observational nutritional studies.

However, studies would have to gather more data through further investigations before nutritional biomarkers could be used widely in clinical and real-world settings.

Journal reference:
  • Sobiecki, J. et al. (2023) "A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study", PLOS Medicine, 20(4), p. e1004221. doi: 10.1371/journal.pmed.1004221. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004221

Posted in: Medical Science News | Medical Research News | Medical Condition News | Healthcare News

Tags: Assay, Biomarker, Body Mass Index, Cancer, Chromatography, Clinical Trial, Cognitive Function, Diabetes, Diet, Fatty Acids, Fish, Liquid Chromatography, Meat, Medicine, Nutrition, Polyphenol, Public Health, Research, Type 2 Diabetes, Vegetables, Wine

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Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

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