We read with great interest the recent article by Chen et al. (1), in which they identified specific metabolites as biomarkers for predicting treatment response and loss of glycemic control in youth with type 2 diabetes. While the study is comprehensive and well-conducted, there are several concerns regarding its methodology and implications. First, the study primarily focuses on the association between metabolite levels and glycemic control outcomes. However, it does not account for the potential influence of dietary intake on metabolite levels (2). Given that diet can significantly impact metabolomics profiles, variations in participants’ dietary habits could confound the observed associations between metabolites and glycemic control. This would help to ensure that the associations observed are indeed due to the metabolites themselves and not influenced by external dietary factors. Second, although this study compares the predictive utility of these circulating metabolomics with known clinical predictors, an external validation cohort should be included to assess the model’s performance. Third, this study provides a snapshot of circulating metabolites and their association with glycemic control, but it does not provide more robust evidence regarding how these biomarkers change over time in relation to glycemic control and diabetes progression. Last, while the study suggests potential clinical applications, the practical use of these biomarkers in routine clinical settings remains unclear. Future research should address how these biomarkers can be integrated into existing clinical workflows, the cost-effectiveness of such interventions, and the extent to which they provide additive value over established measures of glycemic control like HbA1c.

Funding. The authors are grateful for the support of the China Scholarship Council (nos. 202006370051 and 202306370026).

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Handling Editors. The journal editor responsible for overseeing the review of the manuscript was Steven E. Kahn.

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Chen
Z-Z
,
Lu
C
,
Dreyfuss
JM
, et al
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Circulating metabolite biomarkers of glycemic control in youth-onset type 2 diabetes
.
Diabetes Care
2024
;
47
:
1597
1607
2.
Stella
C
,
Beckwith-Hall
B
,
Cloarec
O
, et al
.
Susceptibility of human metabolic phenotypes to dietary modulation
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J Proteome Res
2006
;
5
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2780
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