Comparison of all-cause mortality with different blood glucose control strategies in patients with diabetes in the ICU: a network meta-analysis of randomized controlled trials

Annals of Intensive Care volume 15, Article number: 51 (2025) Published: 09 April 2025

Background

The optimal glucose control strategy for intensive care unit (ICU) patients with diabetes remains a topic of debate. This study aimed to compare the effects of strict glucose control, intermediate strict glucose control, liberal glucose control, and very liberal glucose control on reducing all-cause mortality in ICU patients with diabetes through a network meta-analysis.

Methods

We conducted a search in PubMed, Cochrane Library, Embase, and Web of Science for randomized controlled trials comparing different glucose control strategies in ICU patients with diabetes up to October 1, 2024. The primary outcome was all-cause 90-day mortality. The Risk of Bias 2 tool was used to assess bias in the included studies. Data analysis was performed using Stata (version 17).

Results

A total of 12 randomized controlled trials involving 5,297 participants were included in the final analysis. The results showed that there was no statistically significant difference between the four glucose control strategies in reducing all-cause 90-day mortality. The surface under the cumulative ranking (SUCRA), which was used to rank the strategies and display the probability of each strategy being ranked first, showed the following: intermediate strict control (SUCRA 88%), liberal control (SUCRA 55.3%), very liberal control (SUCRA 40.3%), and strict control (SUCRA 16.5%). The cumulative probability of each strategy’s rank in reducing all-cause mortality, from best to worst, showed that the most likely ranking was intermediate strict control, liberal control, very liberal control, and strict control.

Conclusions

In ICU patients with diabetes, no significant statistical difference was observed among the four glucose control strategies in reducing all-cause 90-day mortality. The SUCRA rankings are hypothesis-generating and require further validation. Therefore, the current evidence is insufficient to definitively conclude that any one strategy is superior to the others in reducing mortality.

Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study—a randomized clinical trial

Intensive Care Medicine Published: 29 September 2021

 

Purpose

Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia management, by targeting the patient’s pre-admission usual glycaemia, could improve outcome.

Methods

In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days.

Results

Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI [64.2%; 70.3%]; CC group: 69.6%, 95% CI [66.7%; 72.5%]). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (p = 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI [1.05; 1.59], p = 0.018).

Conclusion

Targeting an ICU patient’s pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.

Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients

Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients

van Keulen, Kris; Knol, Wilma; Belitser, Svetlana V.; van der Linden, Paul D.; Heerdink, Eibert R.; Egberts, Toine C. G.; Slooter, Arjen J. C.

Critical Care Medicine: September 2018 - Volume 46 - Issue 9 - p 1444–1449

Objectives: To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium.

Design: Prospective cohort study. Setting: Thirty-two–bed mixed intensive care in a tertiary care center. Patients: Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded. Interventions: None.

Measurements and Main Results: The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73–1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15–1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12–2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73–3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16–1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07–2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium.

Conclusions: Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium.

Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients*

Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients*

 by Preiser, Jean-Charles; Lheureux, Olivier; Thooft, Aurelie; Brimioulle, Serge; Goldstein, Jacques; Vincent, Jean-Louis  

Critical Care Medicine: August 2018 - Volume 46 - Issue 8 - p 1224–1229

Objectives: Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5–15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients. Design: Prospective, cluster-randomized, crossover study. Setting: Thirty-five–bed medico-surgical department of intensive care with four separate ICUs. Patients: Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy. Interventions: A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was adjusted to keep blood glucose between 90 and 150 mg/dL using the blood glucose values displayed on the continuous glucose monitor (continuous glucose monitoring group—unblinded units) or according to intermittent blood glucose readings (intermittent glucose monitoring group—blinded units). Measurements and Main Results: The quality and safety of glycemic control were assessed using the proportion of time in range, the frequency of blood glucose less than 70 mg/dL, and the time spent with blood glucose less than 70 mg/dL (TB70), using blood glucose values measured by the continuous glucose monitoring device. Seventy-seven patients were enrolled: 39 in the continuous glucose monitoring group and 38 in the intermittent glucose monitoring group. A total of 43,107 blood glucose values were recorded. The time in range was similar in the two groups. The incidence of hypoglycemia (8/39 [20.5%] vs 15/38 [39.5%]) and the TB70 (0.4% ± 0.9% vs 1.6% ± 3.4%; p < 0.05) was lower in the continuous glucose monitoring than in the intermittent glucose monitoring group. Conclusions: Use of a continuous glucose monitoring–based strategy decreased the incidence and severity of hypoglycemia, thus improving the safety of glycemic control.

Bedside Glucose Monitoring—Is it Safe? A New, Regulatory-Compliant Risk Assessment Evaluation Protocol in Critically Ill Patient Care Settings*

Bedside Glucose Monitoring Is it Safe? A New, Regulatory-Compliant Risk Assessment Evaluation Protocol in Critically Ill Patient Care Settings
DuBois, J et al

Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 567–574

Objectives: New data have emerged from ambulatory and acute care settings about adverse patient events, including death, attributable to erroneous blood glucose meter measurements and leading to questions over their use in critically ill patients. The U.S. Food and Drug Administration published new, more stringent guidelines for glucose meter manufacturers to evaluate the performance of blood glucose meters in critically ill patient settings. The primary objective of this international, multicenter, multidisciplinary clinical study was to develop and apply a rigorous clinical accuracy assessment algorithm, using four distinct statistical tools, to evaluate the clinical accuracy of a blood glucose monitoring system in critically ill patients. 
Design: Observational study. Setting: Five international medical and surgical ICUs. Patients: All patients admitted to critical care settings in the centers. Interventions: None. Measurements and Main Results: Glucose measurements were performed on 1,698 critically ill patients with 257 different clinical conditions and complex treatment regimens. The clinical accuracy assessment algorithm comprised four statistical tools to assess the performance of the study blood glucose monitoring system compared with laboratory reference methods traceable to a definitive standard. Based on POCT12-A3, the Clinical Laboratory Standards Institute standard for hospitals about hospital glucose meter procedures and performance, and Parkes error grid clinical accuracy performance criteria, no clinically significant differences were observed due to patient condition or therapy, with 96.1% and 99.3% glucose results meeting the respective criteria. Stratified sensitivity and specificity analysis (10 mg/dL glucose intervals, 50–150 mg/dL) demonstrated high sensitivity (mean = 95.2%, SD = ± 0.02) and specificity (mean = 95. 8%, SD = ± 0.03). Monte Carlo simulation modeling of the study blood glucose monitoring system showed low probability of category 2 and category 3 insulin dosing error, category 2 = 2.3% (41/1,815) and category 3 = 1.8% (32/1,815), respectively. Patient trend analysis demonstrated 99.1% (223/225) concordance in characterizing hypoglycemic patients. 
Conclusions: The multicomponent, clinical accuracy assessment algorithm demonstrated that the blood glucose monitoring system was acceptable for use in critically ill patient settings when compared to the central laboratory reference method. This clinical accuracy assessment algorithm is an effective tool for comprehensively assessing the validity of whole blood glucose measurement in critically ill patient care settings.

Continuous glucose control in the ICU

Continuous glucose control in the ICU: report of a 2013 round table meeting. Critical Care 2014, 18: 226

Wernerman, J., et al.

http://ccforum.com/content/18/3/226

Achieving adequate glucose control in critically ill patients is a complex but important part of optimal patient management. Until relatively recently, intermittent measurements of blood glucose have been the only means of monitoring blood glucose levels. With growing interest in the possible beneficial effects of continuous over intermittent monitoring and the development of several continuous glucose monitoring (CGM) systems, a round table conference was convened to discuss and, where possible, reach consensus on the various aspects related to glucose monitoring and management using these systems. In this report, we discuss the advantages and limitations of the different types of devices available, the potential advantages of continuous over intermittent testing, the relative importance of trend and point accuracy, the standards necessary for reporting results in clinical trials and for recognition by official bodies, and the changes that may be needed in current glucose management protocols as a result of a move towards increased use of CGM. We close with a list of the research priorities in this field, which will be necessary if CGM is to become a routine part of daily practice in the management of critically ill patients.