Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study

Abstract

Diabetes and frailty are highly prevalent conditions that impact the health status of older adults. Perturbations in protein/amino acid metabolism are associated with both functional impairment and type 2 diabetes mellitus (T2DM). In the present study, we compared the concentrations of a panel of circulating 37 amino acids and derivatives between frail/pre-frail older adults with T2DM and robust non-diabetic controls. Sixty-six functionally impaired older persons aged 70+ with T2DM and 30 age and sex-matched controls were included in the analysis. We applied a partial least squares-discriminant analysis (PLS-DA)-based analytical strategy to characterize the metabotype of study participants. The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 94.1 ± 1.9% for frail/pre-frail persons with T2DM and 100% for control participants. Functionally impaired older persons with T2DM showed higher levels of 3-methyl histidine, alanine, arginine, glutamic acid, ethanolamine sarcosine, and tryptophan. Control participants had higher levels of ornithine and taurine. These findings indicate that a specific profile of amino acids and derivatives characterizes pre-frail/frail older persons with T2DM. The dissection of these pathways may provide novel insights into the metabolic perturbations involved in the disabling cascade in older persons with T2DM.

Specific Metabolites Involved in Antioxidation and Mitochondrial Function Are Correlated With Frailty in Elderly Men

“…It can be deduced that tryptophan, as a radical scavenger, its diminished level could be an important vulnerability for antioxidative defense and might be involved in the pathogenesis of frailty, and overlapped sarcopenia. Notwithstanding, our finding on lower level in tryptophan is not consistent with previous investigation that have reported higher tryptophan concentrations in patients with frailty and type 2 diabetes, according to the European Metabofrail study, which applied a partial least squares-discriminant analysis (PLS-DA)-based analytical strategy to characterize the metabotype (47). Thus, it is essential that further research be performed to confirm the specific role of tryptophan in frailty.…”

Circulating Mitochondrial-Derived Vesicles, Inflammatory Biomarkers and Amino Acids in Older Adults With Physical Frailty and Sarcopenia: A Preliminary BIOSPHERE Multi-Marker Study Using Sequential and Orthogonalized Covariance Selection – Linear Discriminant Analysis

“…Noticeably, derangements in the MQC machinery were documented in intraoperative muscle biopsies obtained from old hip-fractured patients with sarcopenia (Marzetti et al, 2016 ). Finally, phosphoethanolamine was also found among the mediators possibly involved in the disabling cascade in frail older persons with type 2 diabetes mellitus (T2DM) (Calvani et al, 2020b ).…”

“…Its metabolism is mediated by the tryptophan-kynurenine and the tryptophan-methoxyndole pathways, leading to the production of physiologically relevant bioactive compounds, such as NAD, serotonin, and melatonin (Le Floc'h et al, 2011 ). Changes in tryptophan circulating levels have been associated with low muscle quality (Moaddel et al, 2016 ), insulin resistance, and frailty in older adults with T2DM (Chen et al, 2016 ; Marcos-Pérez et al, 2017 ; Calvani et al, 2020b ).…”

Biomarkers of Physical Frailty and Sarcopenia: Coming up to the Place?

“…As such, metabolomics supports the analysis of the dynamic changes of organismal function and provides more informative data than gene or protein expression assays [101][102][103][104]. In the context of PF&S, the study of the dynamic metabolic responses to stressors and the characterization of the biochemical pathways involved are particularly relevant, as this condition is tightly associated with metabolic disorders [105,106].…”