Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise - PubMed (original) (raw)

Clinical Trial

Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise

Jeremy M Robbins et al. JAMA Cardiol. 2019.

Abstract

Importance: Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual's responsiveness to exercise interventions.

Objective: To investigate 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.

Design, setting, and participants: This study involved cross-sectional and longitudinal analyses of 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. White participants with sedentary lifestyles who were free of cardiometabolic disease were included. 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.

Exposures: Plasma DMGV levels.

Main outcome and measures: The association between DMGV levels and measures of body composition, plasma lipids, insulin, and glucose homeostasis before and after exercise training.

Results: Among the 439 participants included in analyses from HERITAGE, the mean (SD) age was 36 (15) years, 228 (51.9%) were female, and the median (interquartile range) body mass index was 25 (22-28). 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 (range of β coefficients, 0.17-0.46 [SEs, 0.026-0.050]; all P < .001, after adjusting for age and sex). After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles (β, 0.14 [95% CI, 0.05-0.23]) and inversely associated with changes in medium and total high-density lipoprotein particles (β, -0.15 [95% CI, -0.24 to -0.05] and -0.19 [95% CI, -0.28 to -0.10], respectively), apolipoprotein A1 (β, -0.14 [95% CI, -0.23 to -0.05]), and insulin sensitivity (β, -0.13; P = 3.0 × 10-3) after exercise training.

Conclusions and relevance: Dimethylguanidino valeric acid is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training. Levels of DMGV may identify individuals who require additional therapies beyond guideline-directed exercise to improve their metabolic health.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Gerszten reported grants from the National Institutes of Health during the conduct of the study. Dr Wang reported grants from the National Institutes of Health during the conduct of the study. Dr Wilson reported grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Rankinen reported grants from National Heart, Lung, and Blood Institute during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.

Figure 1.. Associations Between Dimethylguanidino Valeric Acid Levels and Baseline Metabolic Traits

Effect sizes for each clinical trait are reported per SD increment of dimethylguanidino valeric acid levels in a linear regression model adjusted for age and sex. Black bars with solid diamonds meet Bonferroni statistical significance (P < .001); black bars with open diamonds meet nominal significance (P < .05). HDL indicates high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.

Figure 2.

Figure 2.. Associations Between Dimethylguanidino Valeric Acid Levels and High-Density Lipoprotein (HDL) Traits Responsiveness After 20 Weeks of Exercise Training in the Health, Risk Factors, Exercise Training, and Genetics Study Cohort

Effect sizes for each clinical trait are reported per SD increment of dimethylguanidino valeric acid level based on a generalized linear model adjusted for age and sex. Model 1 is adjusted for baseline levels of each clinical trait. Model 2 further adjusts for age and sex. Model 3 further adjusts for baseline body mass index and changes in body mass index after exercise training.

Figure 3.

Figure 3.. High-Density Lipoprotein (HDL) Particle Total and Subclass Changes After Exercise Training According to Tertile of Baseline Dimethylguanidino Valeric Acid Level

Increasing tertiles of baseline dimethylguanidino valeric acid level from left to right associated with significant decreases in total and medium HDL particle changes after exercise (β [SE], 0.19 [0.043] and 0.18 [0.045]) and nonsignificant decreases in large HDL particles. Relative change is natural logarithmically transformed final value minus log-transformed initial value.

References

    1. Knowler WC, Barrett-Connor E, Fowler SE, et al. ; Diabetes Prevention Program Research Group . Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403. doi: 10.1056/NEJMoa012512 - DOI - PMC - PubMed
    1. Kraus WE, Houmard JA, Duscha BD, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002;347(19):1483-1492. doi: 10.1056/NEJMoa020194 - DOI - PubMed
    1. Hawley JA, Hargreaves M, Joyner MJ, Zierath JR. Integrative biology of exercise. Cell. 2014;159(4):738-749. doi: 10.1016/j.cell.2014.10.029 - DOI - PubMed
    1. Bouchard C, Rankinen T. Individual differences in response to regular physical activity. Med Sci Sports Exerc. 2001;33(6)(suppl):S446-S451. doi: 10.1097/00005768-200106001-00013 - DOI - PubMed
    1. de Lannoy L, Clarke J, Stotz PJ, Ross R. Effects of intensity and amount of exercise on measures of insulin and glucose: analysis of inter-individual variability. PLoS One. 2017;12(5):e0177095. doi: 10.1371/journal.pone.0177095 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources