Impact of intensive insulin therapy on dynamic cardiac function in critically ill patients with stress-induced hyperglycemia

Abstract

BACKGROUND

Stress-induced hyperglycemia (SIH) is common in critically ill patients and has been associated with adverse cardiovascular outcomes. Intensive insulin therapy (IIT) has been proposed to mitigate these risks by achieving tighter glycemic control.

AIM

To evaluate the efficacy of IIT for managing SIH in critically ill patients and to explore its potential effect on cardiac function.

METHODS

A retrospective study was conducted at our hospital from January 2021 to December 2024, adhering to STROBE guidelines. A total of 186 critically ill patients were divided into normal glycemia (n = 85) and SIH (n = 101) groups. The SIH cohort was further subdivided into conventional treatment (n = 50) and IIT (n = 51) groups. Hemodynamic parameters-including right atrial pressure (RAP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PAWP), cardiac output (CO), cardiac index (CI), and B-type natriuretic peptide (BNP)-were measured at baseline and post-treatment. Clinical outcomes such as intensive care unit (ICU) length of stay, mechanical ventilation requirements, and mortality were also recorded. Statistical analyses were conducted using independent samples t-tests and χ²/Fisher’s exact tests.

RESULTS

SIH markedly worsened haemodynamics versus normal glycaemia: RAP 9.8 ± 5.1 vs 6.1 ± 3.5 mmHg, PAP 35.2 ± 16.0 vs 26.2 ± 10.3 mmHg, PAWP 16.0 ± 7.0 vs 8.6 ± 6.4 mmHg, CO 3.3 ± 2.3 vs 6.0 ± 3.3 L/min, CI 1.88 ± 0.24 vs 2.70 ± 0.50 L/min/m², BNP 465 ± 250 vs 180 ± 53 pg/mL (all P < 0.001). Within the SIH cohort, IIT outperformed conventional therapy: RAP 7.0 ± 2.2 vs 8.3 ± 3.9 mmHg (P = 0.04), PAP 21.6 ± 3.7 vs 29.3 ± 6.5 mmHg (P < 0.001), PAWP 10.2 ± 5.4 vs 13.8 ± 5.3 mmHg (P = 0.001), CO 4.9 ± 2.2 vs 4.0 ± 1.4 L/min (P = 0.022), CI 2.58 ± 0.32 vs 2.11 ± 0.31 L/min/m², P < 0.001), BNP 202 ± 62 vs 346 ± 171 pg/mL (P < 0.001). Clinically, IIT shortened ICU stay (10.3 ± 3.4 vs 14.5 ± 2.6 days, P < 0.001), reduced ventilator use (56.9% vs 76.0%, P = 0.042), and lowered mortality (23.5% vs 42.0%, P = 0.048).

CONCLUSION

IIT significantly reduced cardiac filling pressures, improved cardiac function, and was associated with favorable clinical outcomes in SIH patients, suggesting potential benefits of stricter glycaemic control in critically ill patients. However, given the retrospective design and absence of glucose-variability monitoring, these findings should be interpreted with caution.

Key Words: Intensive insulin therapy; Stress-induced hyperglycemia; Cardiac function; Critically ill patients; Intensive care unit

Core Tip: In this study, we aim to explore the effects of intensive insulin therapy (IIT) on cardiac function and clinical outcomes in critically ill patients with stress-induced hyperglycemia. Our findings demonstrate that IIT can significantly improve myocardial performance, reduce hemodynamic stress markers, and result in better clinical outcomes, including shorter intensive care unit (ICU) stays and reduced mortality rates. These findings underscore the potential benefits of stricter glycemic control in the ICU setting, which may ultimately enhance patient recovery and reduce complications.

INTRODUCTION

Stress-induced hyperglycemia (SIH) is a common and clinically significant condition in critically ill patients admitted to the intensive care unit (ICU). Unlike hyperglycemia associated with preexisting diabetes mellitus, SIH arises from the neuroendocrine response to severe illness or injury, characterized by the release of counter-regulatory hormones-such as cortisol, catecholamines, and glucagon-and pro-inflammatory cytokines. This physiological response aims to mobilize energy substrates and sustain vital organ function under stress[1-3]. However, persistent hyperglycemia in the ICU has been associated with increased mortality, longer hospital stays, and a higher risk of complications, including infections and multi-organ dysfunction. Of particular concern is the detrimental impact of SIH on cardiac function, as hyperglycemia can exacerbate myocardial injury, impair contractility, and increase the risk of adverse cardiovascular events. Intensive insulin therapy (IIT) was introduced to achieve tight glycemic control, typically within a narrow therapeutic range. Early studies indicated that IIT could reduce ICU mortality and improve organ function by mitigating the harmful effects of hyperglycemia-such as endothelial dysfunction, oxidative stress, and systemic inflammation[4,5]. Specifically, improved glycemic control may benefit the myocardium by enhancing glucose utilization over fatty acid oxidation and by dampening inflammatory pathways that aggravate cardiac injury. Given the significant role of cardiac complications in ICU morbidity, evaluating the impact of IIT on cardiac function remains a critical area of investigation.

Despite its theoretical and early clinical appeal, IIT remains a topic of ongoing debate. Large-scale clinical trials have reported conflicting outcomes-some demonstrating reduced morbidity and mortality, while others suggest limited benefit or even harm due to hypoglycemia. Hypoglycemia is a significant concern in critically ill patients, as it may precipitate arrhythmias, hemodynamic instability, and neurological injury. Inconsistencies across studies may be attributed to variations in patient populations, glycemic targets, and insulin administration protocols. These discrepancies highlight the need to determine whether IIT provides cardioprotective effects in patients with SIH, particularly across heterogeneous ICU settings[6,7]. Moreover, most prior investigations have emphasized broad outcomes such as mortality, ICU length of stay, and infection rates, rather than direct cardiac performance. While resent studies[8-10] have linked stress hyperglycemia to adverse cardiovascular outcomes, such as increased cardiac filling pressures and reduced output, most research has focused on mortality or infections, with limited attention to IIT's direct impact on cardiac performance. Although evidence suggests that tighter glycemic control reduces hyperglycemia-induced oxidative stress and inflammation, its specific effect on myocardial function remains underexplored. Additionally, the applicability of these findings to diverse ICU populations with varying comorbidities remains unclear. Thus, further investigation into the role of IIT in improving not only survival but also cardiovascular health is essential to optimize clinical management strategies. Hence, a focused evaluation of the relationship between IIT and cardiac function in SIH may offer valuable insights to refine glycemic management strategies and enhance cardiovascular outcomes[11,12].

In light of these considerations, the present study aims to assess the efficacy of IIT in managing SIH among critically ill patients and to investigate its specific impact on cardiac function. The objective is to inform evidence-based ICU glycemic control protocols, ultimately guiding clinicians toward safer and more effective approaches to protect myocardial function and improve patient outcomes.

MATERIALS AND METHODS

Study design

A retrospective evaluation was undertaken at our hospital to assess the efficacy of IIT in managing SIH and its effects on cardiac function among critically ill patients in the ICU. The study spanned from January 2021 to December 2024. The research protocol, methodology, and objectives were designed in accordance with the STROBE guidelines[13]. A total of 186 patients met the above criteria and were enrolled in this analysis. Based on admission blood glucose levels, 85 patients were categorized as having normal glycemia, whereas 101 were classified as exhibiting SIH. Among those with SIH, further subdivision was made according to therapeutic interventions, resulting in two groups: (1) A standard treatment group (n = 50), which received conventional therapy for hyperglycemia; and (2) An IIT group (n = 51), which received strict glycemic control via IIT protocols. Informed consent was obtained from all subjects and/or their legal guardian(s). The study was reviewed and approved by the ethics committee of our hospital (2025-KY2501100013). All procedures were conducted in compliance with relevant guidelines and regulations, adhering to the ethical principles set out in the Declaration of Helsinki. Data confidentiality was maintained, and personal identifiers were removed prior to analysis to protect participant privacy.

Inclusion and exclusion criteria

Eligible patients were those who: (1) Presented with elevated blood glucose upon admission but had no history of diabetes mellitus, insulinoma, or other glucose metabolism disorders; (2) Were found to have normal glycated hemoglobin (HbA1c) levels shortly after admission, suggesting normal pre-illness glycemic status and effectively ruling out preexisting diabetes; (3) Exhibited first-time hyperglycemia during hospitalization; and (4) were severely ill but maintained normal blood glucose levels.

Exclusion criteria encompassed: (1) Acute myocardial infarction; (2) Previously diagnosed diabetes mellitus; (3) Diabetic ketoacidosis or hyperosmolar nonketotic diabetic coma; (4) Severe hepatic or renal dysfunction; (5) Significant cardiac arrhythmias; (6) Active rheumatic heart disease; (7) Severe valvular stenosis or regurgitation; (8) Marked pulmonary artery malformations or severe pulmonary hypertension; and (9) The presence of an implanted cardiac pacemaker.

Treatment methods

Following enrollment, all patients were placed under continuous bedside electrocardiographic monitoring. A Swan-Ganz catheter was inserted via either the internal jugular or subclavian vein to facilitate hemodynamic assessment. Essential resuscitation equipment-including a defibrillator, endotracheal intubation set, and mechanical ventilator-was kept at the bedside, along with emergency pharmacological agents such as lidocaine hydrochloride, dopamine, and epinephrine. All study groups received foundational management aimed at stabilizing the primary condition, preventing and treating infections, minimizing complications, preserving organ function, correcting fluid and electrolyte imbalances, maintaining acid–base homeostasis, and ensuring adequate nutritional support.

SIH was defined as an elevated blood glucose level upon ICU admission (i.e., > 7.0 mmol/L) in patients without a prior history of diabetes, insulinoma, or other glucose metabolism disorders.

Conventional therapy group: Patients in this group received standard supportive measures. When fasting or postprandial blood glucose levels exceeded 15 mmol/L, subcutaneous injections of protaphane insulin (e.g., insulin aspart or equivalent formulation) were administered before breakfast and dinner. The total daily insulin dose was calculated at 0.4-0.6 U/kg/day, with the exact regimen adjusted according to individual patient response.

Intensive therapy group: In contrast, the IIT protocol employed continuous intravenous infusion of regular insulin. A standard preparation was formulated by mixing 40 U of regular insulin with 39 mL of normal saline, yielding a solution concentration of 1 U/mL. An infusion pump was initially set at 0.1 U/kg/hour, and blood glucose was monitored at prespecified intervals. The infusion rate was adjusted according to glycemic readings to maintain tighter glucose control within a target range of 4.4 to 6.1 mmol/L. Blood-glucose levels in the IIT group were checked every 1-2 hours during the first 24 hours and every 2-4 hours thereafter once stable, with additional measurements taken immediately whenever hypoglycemia (< 3.9 mmol/L) was suspected. If hypoglycemia occurred, the insulin infusion was paused, and 20 mL of 50% dextrose was administered intravenously; blood glucose was re-checked after 15 minutes and the infusion restarted at 50% of the previous rate once glucose exceeded 4.4 mmol/L. Persistent or symptomatic hypoglycemia prompted a physician review and repeat dextrose boluses as necessary.

Data collection and outcome measures

Upon admission, right atrial pressure (RAP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PAWP), cardiac output (CO), cardiac index (CI), B-type natriuretic peptide (BNP), partial pressure of oxygen (PaO₂), and partial pressure of carbon dioxide (PaCO₂) were measured for all enrolled patients. Subsequently, comparisons were made between the SIH group and the normal-glycemia group regarding cardiac function parameters, length of stay in the ICU, proportion of patients requiring mechanical ventilation, duration of mechanical ventilation, and mortality rate. In addition, changes in the aforementioned cardiac function indicators before and after treatment were analyzed within both the conventional treatment group and the intensive treatment group.

Statistical analysis

All data analyses were conducted with SPSS software (Version 27.0). Continuous variables following a normal distribution were evaluated using independent samples t-tests, and their findings were reported as mean ± SD. Prior to conducting the t-tests, normality of the data distribution was tested using Shapiro-Wilk tests for continuous variables. The results indicated that the data for all continuous variables followed a normal distribution, justifying the use of independent samples t-tests for comparison. Categorical variables were described in terms of absolute counts and percentages; the χ² test was employed to determine any significant associations. If the assumptions for the χ² test were not satisfied, the Fisher’s exact test was utilized instead. All statistical tests were two-sided, and a P value below 0.05 was used as the threshold for significance.

RESULTS

Baseline characteristics

At baseline, the normal glycemia group comprised 43 males and 42 females (mean age: 63.5 ± 8.9 years; APACHE II score: 20.3 ± 4.1), the conventional therapy group included 25 males and 25 females (mean age: 64.5 ± 9.1 years; APACHE II score: 20.9 ± 3.8), and the IIT group comprised 28 males and 23 females (mean age: 63.8 ± 10.2 years; APACHE II score: 21.3 ± 4.3). No significant differences were observed between the groups in sex distribution, age, or illness severity (all P > 0.05), confirming baseline comparability. All patients exhibited SIH at ICU admission without a prior history of diabetes, insulinoma, or glucose metabolism disorders. Normal HbA1c levels confirmed the absence of preexisting dysglycemia. Hyperglycemia was first documented during hospitalization.

Hemodynamic and biochemical outcomes between the SIH and normal glycemia groups

The SIH group demonstrated marked differences in various hemodynamic and biochemical indices when compared with the normal glycemia cohort. Specifically, the SIH group exhibited significantly elevated RAP, PAP, and PAWP (all P < 0.001), suggesting increased cardiac filling pressures and potential ventricular overload. In addition, the CO and CI values were notably lower in the SIH group (all P < 0.001), indicating compromised myocardial performance. Furthermore, the BNP concentration was substantially higher in patients with SIH (P < 0.001), suggesting a heightened neurohormonal response often associated with cardiac stress. Notably, arterial blood gas parameters revealed divergent patterns between the two groups. Although pH did not significantly differ (P = 0.193), PaO₂ was markedly reduced in the SIH group (P < 0.001), whereas PaCO₂ was considerably lower (P < 0.001), signifying potential respiratory compensation or altered gas exchange (Table 1).

Table 1 Comparison of hemodynamic and biochemical parameters between the stress-induced hyperglycemia and normal glycemia groups.

Parameter	SIH (n = 101)	Normal glycemia (n = 85)	t value	P value
RAP (mmHg)	9.8 ± 5.1	6.1 ± 3.5	5.659	< 0.001
PAP (mmHg)	35.2 ± 16.0	26.2 ± 10.3	4.465	< 0.001
PAWP (mmHg)	16.0 ± 7.0	8.6 ± 6.4	7.467	< 0.001
CO (L/min)	3.3 ± 2.3	6.0 ± 3.3	6.548	< 0.001
CI (L/min/m²)	1.88 ± 0.24	2.70 ± 0.50	14.61	< 0.001
BNP (pg/mL)	465.4 ± 250.0	179.5 ± 52.5	10.35	< 0.001
pH	7.41 ± 0.12	7.38 ± 0.19	1.307	0.193
PaO2 (mmHg)	52.5 ± 11.0	66.0 ± 14.3	7.271	< 0.001
PaCO2 (mmHg)	18.0 ± 6.3	37.9 ± 2.8	26.96	< 0.001

RAP: Right atrial pressure; PAP: Pulmonary artery pressure; PAWP: Pulmonary artery wedge pressure; CO: Cardiac output; CI: Cardiac index; BNP: B-type natriuretic peptide; PaO₂: Partial pressure of oxygen; PaCO₂: Partial pressure of carbon dioxide; SIH: Stress-induced hyperglycemia.

Changes in cardiac function and related indices with conventional vs IIT

At baseline, the two groups showed no statistically significant differences in RAP, PAP, PAWP, CO, CI, BNP, arterial pH, PaO₂, or PaCO₂. However, notable disparities emerged following intervention. Patients in the IIT group exhibited a more pronounced reduction in elevated cardiac filling pressures, as reflected by greater decreases in RAP (P < 0.05), PAP (P < 0.001), and PAWP (P < 0.001), compared with those in the conventional treatment group. Concurrently, a more substantial rise in CO (P = 0.022) and CI (P < 0.001) was observed in the intensive insulin cohort, indicating potential improvements in myocardial performance. Additionally, BNP levels declined more sharply among patients receiving IIT (P < 0.001), suggesting enhanced ventricular function and less cardiac strain. With respect to gas exchange indices, both groups showed improved PaO₂ after treatment (P < 0.001), although the change was more pronounced in the IIT group. In contrast, PaCO₂ levels exhibited divergent patterns; the IIT group had a greater increase in PaCO₂ post-treatment (P < 0.001), potentially reflecting better respiratory efficiency or altered metabolic demands. Notably, blood pH did not differ significantly between groups at either time point, suggesting that neither approach induced detrimental acid–base imbalances (Table 2).

Table 2 Cardiac function and related indices before and after treatment in intensive care unit patients receiving conventional vs intensive insulin therapy (mean ± SD).

Indicator	Conventional treatment group (n = 50)	Intensive insulin therapy group (n = 51)	t value	P value
RAP (mmHg)
Before treatment	9.8 ± 3.59	9.98 ± 3.74	0.247	0.806
After treatment	8.28 ± 3.88a	7.01 ± 2.17a	2.035	< 0.05
PAP (mmHg)
Before treatment	33.5 ± 10.66	34.92 ± 10.61	0.671	0.504
After treatment	29.30 ± 6.47a	21.56 ± 3.67a	7.413	< 0.001
PAWP (mmHg)
Before treatment	16.33 ± 5.93	15.29 ± 7.49	0.773	0.442
After treatment	13.75 ± 5.26a	10.20 ± 5.35a	3.363	0.001
CO (L/min)
Before treatment	3.13 ± 1.60	3.20 ± 1.38	0.236	0.814
After treatment	3.99 ± 1.39a	4.85 ± 2.22a	2.328	0.022
CI [L/(min·m²)]
Before treatment	1.92 ± 0.24	1.96 ± 0.25	0.820	0.414
After treatment	2.11 ± 0.31a	2.58 ± 0.32a	6.700	< 0.001
BNP (pg/mL)
Before treatment	479.23 ± 184.48	452.89 ± 165.03	0.757	0.451
After treatment	345.64 ± 170.86a	202.57 ± 62.11a	5.571	< 0.001
pH
Before treatment	7.34 ± 0.11	7.37 ± 0.13	1.251	0.214
After treatment	7.46 ± 0.19	7.41 ± 0.15	1.469	0.145
PaO2 (mmHg)
Before treatment	56.80 ± 7.95	58.38 ± 8.42	0.969	0.335
After treatment	63.97 ± 10.92a	71.28 ± 11.06a	3.342	0.001
PaCO2 (mmHg)
Before treatment	19.06 ± 6.96	17.65 ± 6.47	1.055	0.294
After treatment	26.59 ± 7.85a	38.35 ± 3.63a	9.694	< 0.001

^aP < 0.05 vs the same group before treatment.

RAP: Right atrial pressure; PAP: Pulmonary artery pressure; PAWP: Pulmonary artery wedge pressure; CO: Cardiac output; CI: Cardiac index; BNP: B-type natriuretic peptide; PaCO₂: Partial pressure of carbon dioxide.

ICU stay and clinical outcomes among three groups

The normal glycemia group consistently exhibited the most favorable outcomes, including shorter ICU hospitalization and lower rates of mechanical ventilation. In contrast, patients receiving conventional therapy experienced prolonged hospitalization (P < 0.001), more frequent ventilator use (P < 0.001), and an elevated mortality rate (P < 0.001) compared with the normal glycemia group. Of particular interest, the IIT group demonstrated improved clinical outcomes compared to the conventional therapy group, manifested by reduced ICU stay (P < 0.001 vs normal; P < 0.001 vs conventional), lower ventilator use (P = 0.0003 vs normal; P = 0.0419 vs conventional), and shorter mechanical ventilation time (P < 0.001 vs normal; P < 0.001 vs conventional). Moreover, mortality was markedly lower in the IIT cohort (P = 0.0061 vs normal; P = 0.0478 vs conventional), suggesting that stricter glycemic control may positively influence survival in critically ill patients. Despite remaining higher than the normal glycemia group, these findings point to the potential benefits of IIT in mitigating the deleterious effects of SIH on overall clinical course and prognosis (Table 3).

Table 3 Comparison of intensive care unit stay and clinical outcomes among three groups, n (%).

Group	ICU stay (mean ± SD)	P value	Ventilator use	P value	Mechanical ventilation time (mean ± SD, h)	P value	Mortality	P value
Conventional treatment group (n = 50)	14.5 ± 2.60a	< 0.001 vs normal	38 (76.0)a	< 0.001 vs normal	121.8 ± 15.8a	< 0.001 vs normal	21 (42.0)a	< 0.001 vs normal
Intensive insulin therapy group (n = 51)	10.3 ± 3.40a,b	< 0.001 vs normal; < 0.001 vs conv.	29 (56.9)a,b	0.0003 vs normal; 0.0419 vs conv.	82.6 ± 13.2a,b	< 0.001 vs normal; < 0.001 vs conv.	12 (23.5)a,b	0.0061 vs normal; 0.0478 vs conv.
Normal glycemia group (n = 85)	7.3 ± 3.74	-	22 (25.9)	-	59.5 ± 11.0	-	6 (7.1)	-

^aP < 0.05 vs the normal glycemia group.

^bP < 0.05 vs the conventional therapy group.

ICU: Intensive care unit.

DISCUSSION

The observed improvement in cardiac function with IIT in critically ill patients with SIH may stem from several interconnected mechanisms. Tight glycemic control reduces myocardial stress induced by hyperglycemia, which leads to oxidative stress, inflammation, and impaired energy metabolism. By enhancing insulin sensitivity, IIT improves myocardial glucose uptake, optimizing substrate utilization and reducing metabolic inefficiencies. Additionally, IIT minimizes blood glucose fluctuations, which are associated with adverse cardiovascular events, further alleviating myocardial strain. These combined effects likely contribute to reduced cardiac filling pressures, improved CO, and enhanced CI[12,14]. Given these mechanisms, IIT should be considered a critical component of the therapeutic strategy for managing critically ill patients with SIH. Implementing IIT protocols may mitigate myocardial dysfunction, reduce adverse cardiovascular outcomes, and improve survival in this high-risk population. Future clinical guidelines should incorporate these findings to support tighter glycemic control in ICU patients.

A central observation of this study was the elevated RAP, PAP, and PAWP among patients with SIH. These measures reflect increased cardiac filling pressures, which can impair ventricular compliance, promote myocardial stretch, and potentially precipitate heart failure. The lower CO and CI in the SIH group further reinforce the notion that hyperglycemia compromises myocardial function, possibly through mechanisms involving oxidative stress, systemic inflammation, and impaired metabolic flexibility. The higher BNP in SIH subjects highlights an additional neurohormonal response, indicative of volume overload and increased left ventricular wall tension. Taken together, these alterations form a pathophysiological basis explaining why hyperglycemia may aggravate cardiac dysfunction in severely ill patients[15,16]. The comparison between conventional therapy and IIT groups underscores the therapeutic value of stricter glycemic control. While both interventions led to reductions in RAP, PAP, and PAWP, these improvements were more pronounced in the intensive insulin group. A key factor may be that sustained hyperglycemia can induce cardiotoxic effects via numerous pathways, including excessive free fatty acid utilization, heightened inflammatory cytokine levels, and the formation of advanced glycation end-products. By tightly regulating blood glucose levels, insulin administration mitigates these pathological processes and shifts the myocardial substrate preference toward glucose, which requires less oxygen consumption and reduces oxidative stress[17,18]. Consequently, enhanced myocardial performance was evident through higher CO and CI post-treatment in the IIT group.

Another mechanism that could have contributed to the observed benefits is the reduction in BNP, a marker of cardiac stress, in the intensive insulin cohort. A sharper decline in BNP in this group may suggest improved left ventricular function and reduced myocardial strain following the correction of hyperglycemia. In addition, the changes in arterial blood gases, particularly the increase in PaO₂ and rise in PaCO₂, could reflect better overall tissue perfusion and respiratory efficiency. Although blood pH remained within acceptable ranges in both groups, the slight alterations in PaCO₂ may indicate different metabolic demands and ventilatory adjustments following therapy[19,20]. Crucially, the clinical relevance of these hemodynamic improvements is supported by the data on ICU stay and mortality. The IIT group demonstrated a shorter hospitalization period and lower mortality rate relative to patients receiving conventional treatment, though they did not reach the outcomes observed in the normal glycemia group. These findings align with prior research suggesting that tight glycemic control may reduce the incidence of infection, facilitate earlier weaning from mechanical ventilation, and foster better organ function. Nonetheless, it is important to acknowledge the potential risks of hypoglycemia, which can be particularly hazardous in critically ill patients[21,22]. Balancing aggressive insulin regimens to achieve optimal glucose targets while avoiding significant hypoglycemic events remains a clinical challenge. The normal glycemia group, serving as a de facto control population, exhibited the most favorable outcomes, underscoring the value of maintaining physiologic glucose levels in preventing cardiovascular stress. However, not all patients are admitted with normal glycemic status, and SIH remains a common challenge in ICU settings. IIT appears to offer a viable strategy to approximate normal glycemia, thereby alleviating detrimental cardiac effects and improving survival prospects[23,24].

In the present study, insulin administration protocols were rigorously standardized to ensure consistent and safe glycemic control. Patients in the conventional therapy group received subcutaneous insulin per institutional guidelines (threshold glucose > 15.0 mmol/L; daily dose: 0.4-0.6 U/kg/day), whereas the IIT group underwent intravenous insulin infusion initiated immediately upon enrollment, titrated hourly to maintain target glucose levels of 6.1-10.0 mmol/L. Adjustments (± 0.02-0.05 U/kg/hour) were algorithm-driven, reflecting international consensus for intensive glucose control in critically ill patients. Hypoglycemia risk was actively managed through frequent (hourly) glucose monitoring, which was safely reduced to bi-hourly once glycemic stability was consistently achieved. A standardized ICU protocol for hypoglycemia (glucose < 4.0 mmol/L) involved immediate cessation of insulin infusion, intravenous administration of 50% dextrose (20-40 mL), and close neurological surveillance with glucose rechecks every 15 minutes. Although mild hypoglycemic episodes occurred in 13.7% of the IIT patients, no severe hypoglycemic events or associated adverse clinical outcomes were observed, supporting the safety profile of the implemented IIT protocol.

Several limitations should be acknowledged. First, the retrospective, single-center design inherently carries a risk of selection and information bias, and residual confounding cannot be excluded despite careful chart review; hence causal inference is limited. Future multicenter prospective studies are necessary to validate external applicability, particularly in ICU populations with comorbidities such as diabetes or chronic cardiovascular disease. Second, detailed metrics of glucose variability were not captured, and continuous glucose-monitoring systems were not used; consequently, we may have underestimated transient hypo- or hyperglycaemic excursions that could influence outcomes. Third, the absence of uniform echocardiographic follow-up limits mechanistic interpretation of myocardial recovery beyond invasive haemodynamic data. Fourth, subgroup analyses to identify patients most likely to benefit from IIT were not feasible owing to sample size and study design but will be prioritised in future cohorts. Additionally, variations in concurrent treatments and baseline comorbidities may have influenced outcomes. While IIT demonstrated clinical benefits, including reductions in myocardial stress, ICU stay, and mortality, it also poses practical challenges such as the need for frequent glucose monitoring, the risk of hypoglycaemia, and the requirement for individualised insulin titration. To enhance mechanistic insight, future studies should incorporate cardiac-specific biomarkers and advanced imaging modalities to evaluate myocardial injury and functional recovery with greater precision.

CONCLUSION

In summary, our retrospective analysis suggests that IIT may reduce cardiac filling pressures, improve CO, and lower BNP levels in critically ill patients with SIH, with accompanying trends toward shorter ICU stays, less ventilator dependence, and lower in‐hospital mortality compared with conventional therapy. Prospective, multicenter trials with detailed echocardiographic assessment and predefined subgroup stratification are needed to validate and generalize these findings.

ACKNOWLEDGEMENTS

We thank all the patients and the staff who participated in this study.