Stress Hyperglycemia Ratio: A Simple Biomarker with Big Implications for Exposure-Related Malnutrition (ERM)

A new study in BMC Infectious Diseases (Feng et al., 2025) has shed light on the prognostic value of the stress hyperglycemia ratio (SHR) in critically ill, non-diabetic patients with sepsis. Drawing on 1,200 cases from the MIMIC-IV database, the researchers asked a simple question:

Can SHR predict mortality risk better than glucose alone?

The answer was a clear yes.

Patients in the highest SHR quartile had double the risk of in-hospital and ICU death compared to those in the lowest quartile—even after adjusting for age, comorbidities, and severity scores. Interestingly, the relationship was U-shaped, meaning both very low and very high SHR carried risk.

Why does this matter?

Sepsis is the ultimate stress test for the body. Under the assault of infection and inflammation, hormones and cytokines push glucose levels up to fuel immune defense. But when this acute hyperglycemia is out of proportion to a patient’s long-term glycemic background (as measured by HbA1c), it signals something more dangerous: maladaptation.

Inflammation drives insulin resistance, dampening the normal signal that channels glucose into muscle and immune cells. The result is substrate misallocation: high glucose in the bloodstream, but insufficient energy where it is most needed for defense and repair. This is precisely the kind of trade-off that defines Exposure-Related Malnutrition (ERM)—a state where the body cannot balance demand and reserve under stress.

SHR as a window into ERM staging

The ERM framework proposes that resilience and vulnerability can be mapped across stages of exposure, adaptation, maladaptation, and exhaustion. SHR offers a simple, quantifiable way to place patients on that trajectory:

• Adaptive stage: SHR close to 1 — stress response proportional to background glycemia.

• Trade-off stage: SHR modestly elevated (1.2–1.5) — early signs of insulin resistance, still compensatory.

• Maladaptation stage: SHR high (>1.5) — marked hyperglycemia with impaired tissue uptake, fueling inflammation and endothelial injury.

• Exhaustion stage: SHR low (<0.9) despite stress — failure to mount a glycemic response, reflecting substrate depletion and systemic collapse.

Because SHR requires only two routine tests—admission glucose and HbA1c—it is accessible in most hospitals worldwide. Adding it to ERM staging would strengthen our ability to detect early substrate misallocation and identify high-risk patients before irreversible decline.

Moving forward

This study confirms what ERM theory anticipates: when the stress response overwhelms energy allocation, outcomes worsen. SHR is not just a diabetes metric—it is a marker of metabolic resilience under stress.

Integrating SHR into ERM staging models could bridge critical care and resilience science, helping clinicians move beyond static lab values to dynamic markers of adaptation and maladaptation. In time, such tools may guide more personalized interventions—from tighter glucose modulation to early nutrition and metabolic support—aimed at restoring balance rather than chasing numbers.

Reference:

Feng S, Zou R, Wang Y, Huang Y, Zhou Q, Huang Q, Xu H. Stress hyperglycemia ratio as a mortality predictor in non-diabetic septic patients: a retrospective cohort analysis. BMC Infect Dis. 2025;25:752. doi:10.1186/s12879-025-11151-7

#Stress Hyperglycemia Ratio (SHR), #Sepsis Prognosis, #Insulin Resistance, #Exposure-Related Malnutrition (ERM), #Metabolic Resilience