Stress-induced hyperglycemia and mortality of non-diabetic patients with sepsis: a meta-analysis

Jiayang HuangJunwei LiXiaowen ChenJiayu Gu^*

• Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China

Stress-induced hyperglycemia (SIH) is a common metabolic response in critically ill patients, but its prognostic significance in non-diabetic patients with sepsis remains unclear. We conducted a meta-analysis to evaluate the association between SIH and short-term mortality in this population. PubMed, Embase, and Web of Science were searched for relevant observational studies. SIH was defined by study-specific early admission blood glucose cutoffs. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model by incorporating the influence of heterogeneity. Thirteen studies encompassing 53,073 non-diabetic septic patients were included. Overall, SIH was associated with significantly increased mortality (RR = 1.75, 95% CI: 1.45–2.11, p < 0.001; I² = 72%), with a 95% prediction interval of 1.18–2.61, indicating that the association is expected to persist in most future study populations despite heterogeneity. Subgroup analyses confirmed the association across prospective and retrospective/post-hoc studies (RR: 2.01 vs. 1.63, p = 0.29), different sepsis severities (RR: 1.60 vs. 2.26, p = 0.12), diagnostic criteria (Sepsis-2.0: 1.84 vs. Sepsis-3.0: 1.73, p = 0.80), timing of SIH assessment (at admission, within 24 h, or 48 h; p = 0.16), and glucose cutoffs (7.8, 11.1, 16.7 mmol/L; p = 0.34). Notably, SIH showed a stronger association with ICU/in-hospital mortality (RR = 2.25) compared with 1-month (1.63) or 3–12-month mortality (1.35; p = 0.001). Meta-regression showed no significant effect of study characteristics (p all > 0.05). In conclusion, SIH defined by early admission blood glucose is significantly associated with increased short-term mortality in non-diabetic septic patients. These findings highlight the importance of early recognition and monitoring of SIH in this high-risk population.