NMR in Personalized Medicine: Tech Can Identify Biomarkers of Metabolic Syndrome

by Óscar Millet, Principal Investigator at the CIC bioGUNE, Spain

Metabolic syndrome (MetS) is a group of five risk factors that when left untreated increase the likelihood of developing heart disease, diabetes, and stroke. It may also be called syndrome X or insulin resistance syndrome. One quarter of the developed world population is estimated to have the condition. It is associated with the risk of coronary heart disease, stroke and other conditions that affect the blood vessels.Individuals with MetS are also more susceptible to other conditions, from asthma and polycystic ovary syndrome to fatty liver and cancers of the prostate, pancreas and breast.

Óscar Millet, Principal Investigator at the CIC bioGUNE in Bilbao, Spain, has been actively involved in MetS research for many years. Millet and his team are using nuclear magnetic resonance (NMR)-based in vitro diagnostic regulation (IVDr) platform to characterize biomarkers of MetS at different stages of its progression, with the aim of identifying a person’s risk of the disease prior to symptoms developing. As the disease is both preventable and reversible, this information could eventually lead to lower instances of the disease. The resulting benefits to individuals and healthcare systems could be significant.

MetS diagnosis

In 2020, an estimated 2.5 million children and 35.5 million adolescents were living with MetS.¹ As well as affecting quality of life for patients, this places a substantial burden on healthcare systems, and has far reaching socioeconomic implications that have been described as “a medical challenge for the whole research community.”²

The definition of MetS is controversial, but diagnosis of MetS is usually determined by the presentation of at least three of the following four factors: abdominal obesity (a waist measurement of 40+ inches for men and 35 inches for women), high blood sugar (100mg/dL or more), high serum triglycerides (150mg/dL or more) and low high-density lipoprotein (less than 40mg/dL for men, 50mg/dL or less for women). A joint statement by several bodies, including the International Diabetes Federation and the American Heart Association, recognized that, although waist circumference is an important signifier of MetS, this does not account for differences in sex and across ethnic groups.³

Traditional molecular markers have been found too imprecise to detect the disease at earlier stages.

“There is a need to obtain novel molecular markers of pre-disease stages – a bottleneck that slows down personalized nutrition in metabolomics,” said Julia Hernandez-Baixauli et. al, in their 2020 publication “Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment.”

NMR in metabolomics

For many analytical scientists, NMR is a go-to technique. It is robust, reliable, and non-destructive, and its quantitative capabilities offer high coverage and low detection limits. In the analysis of biofluids, the metabolism that can be measured with NMR is statistically significant, so, the resulting spectral data are very high quality.

NMR can be applied in the characterization of disease biomarkers and also in the evaluation of the prognosis of the disease by analyzing different samples throughout disease progression.

One of the major advantages of using NMR spectroscopy is its reproducibility. NMR is both intra- and inter-reproducible, and allows the quantification of metabolites in a single acquisition, and these measurements will be exactly the same in any lab across the world.

NMR spectroscopy has emerged in recent years as a powerful analytical technique in the field of metabolomics. Its reproducibility, quantitative measurements, and ability to identify metabolites in complex mixtures make it a key technology in the study of metabolomics and other scientific areas.

Biomarker identification for Mets

Millet’s team has built up a cohort of 15,000 people and collected more than 90,000 samples in the local biobank. Their research into MetS involves collecting serum and urine samples from people at different stages of the disease and comparing them to the available medical data.

Using NMR spectroscopy on serum and urine samples, the team has developed a predictive model for MetS,⁴ which, when fully validated and translated into the clinic, could help the medical community to better predict and therefore help prevent the disease.

Large-scale studies such as this allow biomarkers to be identified that are relevant to subgroups of people. Madhusoodanan highlighted how traditional biomarkers are not accurate predictors of MetS in women, nor in people of color globally—meaning research at the population scale will help identify more relevant biomarkers.⁵

Toward a precision medicine approach for MetS

Millet’s work demonstrates that NMR spectroscopy has the potential to help make personalized precision medicine a reality. NMR’s ability to analyze a large sample cohort is important when validating complex biological samples, meaning it can help provide valuable insight into MetS and many other diseases.

About the author

After obtaining a Ph.D. in Organic Chemistry (University of Barcelona, 1999), Óscar Millet joined the Lewis Kay group in Toronto for a post-doctoral stay (University of Toronto, 2000-2004). He was then the recipient of a Ramon y Cajal reincorporation contract at the Parc Cientific de Barcelona (2004-2006), and is currently group leader at the CIC bioGUNE. His research focuses on the use of nuclear magnetic resonance (NMR) in the study of biologically relevant proteins and enzymes, particularly the delicate balance between protein stability and dynamics. Such knowledge is applied in the development of new compounds with therapeutic activity, specifically in the field of rare diseases. He has published more than 125 papers with over 5500 citations (1998-2023) and an h-index of 33.

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