Relationship between stress hyperglycaemic ratio (SHR) and critical illness: a systematic review

Abstract

Stress-induced hyperglycemia (SIH) is a physiological response to acute or chronic stress characterized by elevated blood glucose levels. It is prevalent in both patients with and without diabetes, particularly those with acute or critical illnesses. The development of SIH is characterized by complex interactions among catecholamines, cortisol, and inflammatory mediators such as cytokines, resulting in increased hepatic glucose production and insulin resistance. While mild to moderate SIH may provide a protective mechanism during stress, prolonged or excessive hyperglycemia can exacerbate inflammation and oxidative stress, contributing to adverse outcomes in conditions such as acute myocardial infarction, heart failure, and cerebrovascular diseases. The stress-hyperglycemia ratio (SHR), defined as the ratio of admission glucose to estimated mean glucose (derived from glycated hemoglobin [HbA1c]), has emerged as a valuable tool for quantifying stress hyperglycemia. Unlike absolute glucose levels, the SHR accounts for background hyperglycemia and provides a more accurate indicator of the relative glucose elevation associated with critical illness. Extensive research has demonstrated a U-shaped or J-shaped relationship of the SHR with disease outcomes, indicating that both low and high SHRs are associated with increased mortality and morbidity. The SHR has shown significant predictive value in cardiovascular diseases (e.g., acute coronary syndrome, heart failure), cerebrovascular diseases (e.g., acute ischemic stroke, intracerebral hemorrhage), and infectious diseases (e.g., sepsis, pneumonia). It also plays a role in other conditions, such as acute pancreatitis and certain cancers. The ease of calculating the SHR from widely available admission glucose and HbA1c tests makes it a practical and valuable prognostic marker in clinical settings. This review examines the relationship between the SHR and critical illnesses, highlighting its mechanisms and predictive value across various diseases.

Keywords: Cardiovascular disease; Cerebrovascular disease; Critical illness; Insulin resistance; Prognostic marker; Stress-hyperglycemia ratio (SHR); Stress-induced hyperglycemia (SIH).

Fig. 1

The mechanism between SIH and diseases. A In the disease state, the stress response, through the activation of the sympathetic nervous system and the endocrine system, causes an increase in the secretion of adrenaline, noradrenaline, cortisol, etc. Among them, adrenaline and noradrenaline can promote the breakdown of glycogen in the liver and muscles, releasing glucose into the blood. Cortisol will increase blood glucose levels by promoting gluconeogenesis in the liver. B Chronic stress can lead to insulin resistance by upregulating inflammatory factors and oxidative stress levels, resulting in post-receptor insulin signaling defects and downregulation of glucose transporter (GLUT). C Inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), NADPH oxidase-2 (NOX2), and NADPH oxidase-1 (NOX1) can disrupt the body’s metabolic pathways and interfere with the normal action of insulin, thereby promoting insulin resistance. Tumor necrosis factor-α (TNFα) may promote gluconeogenesis by stimulating the production of glucagon. D The U-shaped association between SHR and critically ill patients. Moderate SHR helps optimize cellular glucose uptake while avoiding hyperosmolar reactions. Low and high SHR levels are associated with more adverse disease outcomes and increased mortality. SIH: Stress-induced Hyperglycaemia, SHR: Stress Hyperglycaemia Ratio