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Observational Study
. 2025 Jun 18:16:1518746.
doi: 10.3389/fendo.2025.1518746. eCollection 2025.

The association between stress hyperglycemia and poor outcome in critically ill children is modulated by hyperlactatemia

Wenjun Liu  1 , Milan Dong  2 , Jing Li  1 , Guoying Zhang  3 , Ju Chen  3 , Jianyu Jiang  4 , Ling Duan  4 , Daoxue Xiong  4 , Bo Huang  5 , Yingbo Zou  5 , Fuyan Liu  5 , Hongmin Fu  6 , Kai Yu  6
Affiliations
Observational Study

The association between stress hyperglycemia and poor outcome in critically ill children is modulated by hyperlactatemia

Wenjun Liu et al. Front Endocrinol (Lausanne). .

Abstract

Background: The available evidence on tight glycemic control is conflicting, while the interaction between glucose and lactate in critically ill children remains unclear.

Objective: To explore the potential role of hyperlactatemia (HL) in modulating the relationship between stress hyperglycemia (SHG) and poor outcomes, aiming to establish tailored glucose targets in critically ill children.

Methods: This was a secondary analysis of a prospective observational cohort study conducted in five Pediatric Intensive Care Units (PICU) in southwestern China (ChiCTR2000030846). The interaction effect between glucose and lactate metrics concerning outcomes and subsequent subgroup regression analysis was conducted. SHG was defined as glucose > 150 mg/dL(8.3mmol/L) and HL as lactate > 2 mmol/L.

Results: A cohort of 433 pediatric patients with 4885 arterial blood gas measurements were finally enrolled. 90 (20.8%) cases died within 28 days of PICU admission. Significant interaction effects between SHG and HL on outcomes were observed (p < 0.05). In the non-HL group, SHG was not an independent predictor of 28-day mortality (p = 0.656) and was not correlated with either 28-day ventilator-free days (p = 0.916) or 28-day ICU-free days (p = 0.914). In contrast, in the HL group, SHG was independently associated with 28-day mortality (OR 3.55, 95% CI 1.62~7.80, p = 0.002) and correlated with a reduction of 5.04 28-day ventilator-free days (p = 0.003) and 4.10 28-day ICU-free days (p = 0.004).

Conclusions: HL potentially modulates the correlation between SHG and poor outcomes in pediatric critically ill patients. Combined SHG and HL are associated with poor outcomes, whereas SHG without HL is not.

Keywords: children; critically ill; hyperlactatemia; outcome; stress hyperglycemia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart illustrating participant selection for the study.
Figure 2
Figure 2
Three-dimensional column diagram of lactate and glucose quartiles related to 28-day mortality. (A) The combined highest Lacmean and Glumean quartiles (upper-right column) indicated the highest 28-day mortality, whereas relatively low Lacmean even with the highest Glumean didn’t correlate with high 28-day mortality (upper-left columns); (B) For the combination of Lactwmean and Glutwmean, their highest quartiles (upper-right column) corresponded to peak 28-day mortality. However, lower Lactwmean remained unrelated to high mortality, even with the highest Glutwmean (upper-left columns); (C) The combined highest Lacmean and Glumax quartiles (upper-right column) corresponded to the highest 28-day mortality, while relatively low Lacmean, even at the highest Glumean quartiles, showed no association with elevated mortality (upper-left columns). Lacmean, mean lactate concentration; Lactwmean, time-weighted mean lactate; Lacmax, maximum lactate concentration. Glumean, mean glucose concentration; Glutwmean, time-weighted mean glucose; Glumax, maximum glucose concentration.
Figure 3
Figure 3
Comparison of 28-day Mortality between SHG and non-SHG group across HL and non-HL Subgroups. † p, the p-value from the Breslow-Day test (= 0.007) of Cochran-Mantel- Haenszel test, indicates a significant difference in the odds ratios (ORs) of the association between SHG and 28-day mortality between the HL and non-HL groups. *, the difference between groups was significant.
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