Biomarker Predicts Ability of Endurance Training to Improve Metabolic Health

Levels of the biomarker dimethylguanidino valeric acid in the blood are predicative of whether an individual can improve overall metabolic health through endurance training.

Considering the variable metabolic responses to exercise training, investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) examined the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before and after 20 weeks of endurance exercise training. The choice of DMGV was based on previous findings, which showed that the molecule was a marker of liver fat and that circulating levels were linked to the development of type II diabetes up to 12 years prior to disease onset.

For the current study, the investigators determined blood levels of DMGV in nearly 440 otherwise healthy participants in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study - a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997 - before and after a chronic exercise training program. Metabolomic tests were performed using a liquid chromatography, tandem mass spectrometry method on plasma samples collected before and after exercise training in the HERITAGE study. Metabolomics and data analysis were performed from August 2017 to May 2018.

Results revealed that baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides, and inversely associated with insulin sensitivity, low-density lipoprotein cholesterol, high-density lipoprotein size, and high-density lipoprotein cholesterol. After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles and inversely associated with changes in medium and total high-density lipoprotein particles and apolipoprotein A1, and insulin sensitivity after exercise training.

The results were interpreted to mean that DMGV was associated with adverse metabolic risk even in very young individuals free of overt disease. Regular exercise modulated circulating levels of DMGV, and these changes correlated with the changes in associated clinical traits after exercise training. Furthermore, higher baseline levels of DMGV were associated with reduced improvements in lipid traits and insulin sensitivity after exercise training.

"In our earlier work, what we found particularly compelling was the fact that patients who underwent weight loss surgery had decreases in DMGV,” said senior author Dr. Robert Gerszten, chief of cardiovascular medicine at Beth Israel Deaconess Medical Center. “In this new study, we were curious to see if exercise could also modulate levels of DMGV. Our findings indicate that DMGV levels may identify individuals who are less responsive to the metabolic health benefits of endurance exercise training and may require additional therapies beyond guideline-directed exercise to improve their metabolic health. These results highlight the potential application of metabolomics to inform targeted exercise therapy.”

The study was published in the June 5, 2019, online edition of the journal JAMA Cardiology.

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