Letter to the editor regarding to ‘impact of time from blood specimens collection to centrifugation on the diagnosis of gestational diabetes mellitus’

To the Editor

The paper addresses an important and often underappreciated pre-analytical issue: glycolysis-related glucose loss before plasma separation may lead to underdiagnosis of gestational diabetes mellitus (GDM) [1]. The authors’ combined prospective and real-world approaches are clinically relevant. However, I would like to raise three points for further discussion.

First, the clinical question is not merely whether delayed centrifugation lowers measured glucose (it does), but whether the observed diagnostic impact would persist under contemporary inhibitor-containing collection systems. Multiple studies have shown that the traditional sodium fluoride (NaF) tube incompletely inhibits early glycolysis, whereas citrate buffer-based additives provide more rapid stabilization and can materially change measured glucose when processing is delayed [2]. Without an explicit description and stratified analysis by tube/additive (and whether sample handling complied with current analytical guidance), it is difficult for clinicians to know whether the study’s effect size is primarily a ‘workflow’ problem or a ‘collection system’ problem. This distinction matters because switching to more effective inhibitors may be a faster, system-wide intervention than attempting to eliminate delays during high-throughput OGTT clinics.

Second, the manuscript reports reduced GDM rates with longer delays, but a clinically actionable estimate would be the patient-level reclassification across IADPSG/WHO thresholds, ideally with sensitivity analyses around each time point (fasting, 1 h, 2 h). Small downward shifts can disproportionately affect those near cutoffs. Prior diagnostic frameworks based on hyperglycemia and pregnancy outcomes emphasize that risk increases continuously across glucose distributions rather than at sharp biologic boundaries [3]. Therefore, beyond incidence differences, presenting the proportion of women who cross from ‘positive’ to ‘negative’ (and which time point drives it) would better inform counseling and quality improvement (e.g. whether a clinic should prioritize rapid separation for the 1 h and 2 h draws, or reconsider the entire OGTT pathway).

Third, even if the authors avoid assuming equal glycolysis effects, the clinical consequence of a given decrement is not equivalent at fasting vs post-load values because their proximity to cutoffs, analytic imprecision, and within-person biological variability differ [4]. A more clinically intuitive approach would be to model each specimen’s processing time as a continuous predictor and estimate the probability of meeting each diagnostic criterion, then compute marginal effects on overall GDM diagnosis [5]. This would also allow laboratories to set pragmatic ‘time-to-separation’ targets for each draw rather than relying on an aggregate score that may be difficult to operationalize in practice.

In summary, this work reinforces that pre-analytical handling can meaningfully influence GDM diagnosis. Clarifying the collection system, quantifying patient-level reclassification, modeling time effects per specimen, and linking results to implementable laboratory quality metrics would strengthen clinical applicability and ensure that workflow changes deliver measurable improvements in maternal-fetal care.

Funding Statement

No funding was received for this work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.