Time-weighted Average Glucose Research Articles

Relationship between time-weighted average glucose and mortality in critically ill patients: a retrospective analysis of the MIMIC-IV database

Blood glucose management in intensive care units (ICU) remains a controversial topic. We assessed the association between time-weighted average glucose (TWAG) levels and ICU mortality in critically ill patients in a real-world study. This retrospective study included critically ill patients from the Medical Information Mart for Intensive Care IV database. Glycemic distance is the difference between TWAG in the ICU and preadmission usual glycemia assessed with glycated hemoglobin at ICU admission. The TWAG and glycemic distance were divided into 4 groups and 3 groups, and their associations with ICU mortality risk were evaluated using multivariate logistic regression. Restricted cubic splines were used to explore the non-linear relationship. A total of 4737 adult patients were included. After adjusting for covariates, compared with TWAG ≤ 110 mg/dL, the odds ratios (ORs) of the TWAG > 110 mg/dL groups were 1.62 (95% CI 0.97–2.84, p = 0.075), 3.41 (95% CI 1.97–6.15, p < 0.05), and 6.62 (95% CI 3.6–12.6, p < 0.05). Compared with glycemic distance at − 15.1–20.1 mg/dL, the ORs of lower or higher groups were 0.78 (95% CI 0.50–1.21, p = 0.3) and 2.84 (95% CI 2.12–3.82, p < 0.05). The effect of hyperglycemia on ICU mortality was more pronounced in non-diabetic and non-septic patients. TWAG showed a U-shaped relationship with ICU mortality risk, and the mortality risk was minimal at 111 mg/dL. Maintaining glycemic distance ≤ 20.1 mg/dL may be beneficial. In different subgroups, the impact of hyperglycemia varied.

Impact of the Time-Weighted Average Glucose Concentration and Diabetes on In-Hospital Mortality in Critically Ill Patients Older Than 75 Years: A Retrospective Cohort Study

ObjectiveTo evaluate the effects of diabetes and hyperglycemia on in-hospital mortality in critically ill patients older than 75 years. MethodsThis was a single-center retrospective cohort study of patients older than 75 years in the first intensive care unit stay. The patients were divided into the following 4 groups: time-weighted average glucose (TWAG) <140 mg/dL without diabetes (group 1), TWAG ≥140 mg/dL without diabetes (group 2), TWAG <180 mg/dL with diabetes (group 3), and TWAG ≥180 mg/dL with diabetes (group 4). Clinical and laboratory data were analyzed. ResultsA total of 6760 patients over 75 years of age were included, including 2089 patients previously diagnosed with diabetes. The patients in group 2 had the highest in-hospital mortality (27.4%). In the fully adjusted regression model, the risk of in-hospital mortality increased by 76% (odds ratio = 1.76, 95% CI: 1.49-2.08) in group 2 as compared with group 1. Those from groups 3 and 4 exhibited risks equivalent to the risks of those in group 1; similar results were observed in the subgroup analysis. A J-shaped curve relationship and threshold effect were observed in patients without diabetes. For those with diabetes, a flatter curve pattern with a small slope was observed. ConclusionStress hyperglycemia was more detrimental to short-term prognosis than diabetes status in these patients. Looser glucose control may be suitable for patients older than 75 years with diabetes but unnecessary for those without diabetes. Patients with diabetes may be more resistant to the detrimental effects of glucose variations.

Glycemic control in critically ill patients with or without diabetes

BackgroundEarly randomized controlled trials have demonstrated the benefits of tight glucose control. Subsequent NICE-SUGAR study found that tight glucose control increased mortality. The optimal glucose target in diabetic and nondiabetic patients remains unclear. This study aimed to evaluate the relationship between blood glucose levels and outcomes in critically ill patients with or without diabetes.MethodsThis was a retrospective analysis of the eICU database. Repeat ICU stays, ICU stays of less than 2 days, patients transferred from other ICUs, those with less than 2 blood glucose measurements, and those with missing data on hospital mortality were excluded. The primary outcome was hospital mortality. Generalised additive models were used to model relationship between glycemic control and mortality. Models were adjusted for age, APACHE IV scores, body mass index, admission diagnosis, mechanical ventilation, and use of vasopressor or inotropic agents.ResultsThere were 52,107 patients in the analysis. Nondiabetes patients exhibited a J-shaped association between time-weighted average glucose and hospital mortality, while this association in diabetes patients was right-shifted and flattened. Using a TWA glucose of 100 mg/dL as the reference value, the adjusted odds ratio (OR) of TWA glucose of 140 mg/dL was 3.05 (95% confidence interval (CI) 3.03–3.08) in nondiabetes and 1.14 (95% CI 1.08–1.20) in diabetes patients. The adjusted OR of TWA glucose of 180 mg/dL were 4.20 (95% CI 4.07–4.33) and 1.49 (1.41–1.57) in patients with no diabetes and patients with diabetes, respectively. The adjusted ORs of TWA glucose of 80 mg/dL compared with 100 mg/dL were 1.74 (95% CI 1.57–1.92) in nondiabetes and 1.36 (95% CI 1.12–1.66) in patients with diabetes. The glucose ranges associated with a below-average risk of mortality were 80–120 mg/dL and 90–150 mg/dL for nondiabetes and diabetes patients, respectively. Hypoglycemia was associated with increased hospital mortality in both groups but to a lesser extent in diabetic patients. Glucose variability was positively associated with hospital mortality in nondiabetics.ConclusionsTime-weighted average glucose, hypoglycemia, and glucose variability had different impacts on clinical outcomes in patients with and without diabetes. Compared with nondiabetic patients, diabetic patients showed a more blunted response to hypo- and hyperglycemia and glucose variability. Glycemic control strategies should be reconsidered to avoid both hypoglycemia and hyperglycemia.

Intraoperative hyperglycemia in patients with an elevated preoperative C-reactive protein level may increase the risk of acute kidney injury after cardiac surgery.

The effect of hyperglycemia on acute kidney injury (AKI) in patients undergoing cardiac surgery is unclear and may involve as yet unexplored factors. We hypothesized differential effects of intraoperative hyperglycemia on AKI after cardiac surgery depending on baseline inflammatory status, as reflected by the C-reactive protein (CRP) level. This retrospective study included patients who underwent cardiac surgery seen at our hospital from 2008 to 2018. Patients were classified into four groups according to their preoperative CRP level (≥ 1 or < 1mg/dl) and their intraoperative time-weighted average glucose concentration (> 140 or ≤ 140mg/dl): low CRP and normoglycemia, low CRP and hyperglycemia, high CRP and normoglycemia, and high CRP and hyperglycemia. The data were analyzed by multivariable logistic regression analysis. The data of 3625 patients were analyzed. The logistic regression showed that patients in the high CRP and hyperglycemia group had a significantly higher risk of AKI than patients in the low CRP and normoglycemia group [odds ratio (OR), 1.58; 95% confidence interval (CI) 1.10-2.27], low CRP with hyperglycemia group (OR, 1.69; 95% CI 1.16-2.47) and high CRP with normoglycemia group (OR, 1.50; 95% CI 1.01-2.23). Intraoperative hyperglycemia in patients with an elevated preoperative CRP level was significantly related to an increased risk of AKI after cardiac surgery. Individualized perioperative glycemic control may therefore be necessary in these patients.

Hyperglycemia as a risk factor for postoperative early wound infection after bicondylar tibial plateau fractures: Determining a predictive model based on four methods

ObjectivesIdentify a glucose threshold that would put patients with isolated bicondylar tibial plateau fractures at risk of early wound infection (i.e. < 90 days). DesignRetrospective review of medical records. SettingAcademic American College of Surgeons (ACS) Level 1 trauma center. PatientsAdult patients between 2010 and 2015 with an operatively treated isolated bicondylar tibial plateau fracture and at least three glucose measurements during their hospitalization. Main Outcome MeasurementTo predict infection using four different methods: maximum preoperative blood glucose (PBG), maximum blood glucose (MGB), Hyperglycemic Index (HGI), and Time-Weighted Average Glucose (TWAG). Results126/381 patients met our inclusion criteria. Fifteen (12%) patients had an open fracture and 30/126 (23%) developed an infection. Median glucose for each predictive method studied was 114 (IQR 101.2–137.8) mg/dL for PBG, 144 (IQR 119–169.8) mg/dL for MBG, 0.8 (IQR 0.20–1.60) mmol/L for HGI, and 120.4 (IQR 106.0–135.6) mg/dL for TWAG. As expected, infected patients had higher PBG, MGB, and TWAG. HGI was similar in both groups. None of these differences prove to be statistically significant (p > .05). Logistic regression models for all the methods showed that having an open fracture was the strongest predictor of infection. ConclusionIt is well known that stress-induced hyperglycemia increases the risk of infection, we present and compare four models that have been used in other medical fields. In our study, none of the methods presented identified a glucose threshold that would increase the risk of infection in patients with bicondylar tibial plateau fractures.Level of Evidence: Retrospective review, Level III. See Instructions for Authors for a complete description of levels of evidence.

Intraoperative glucose variability, but not average glucose concentration, may be a risk factor for acute kidney injury after cardiac surgery: a retrospective study.

Altered perioperative glycemic control may contribute to the development of renal dysfunction in cardiac surgery patients. Nevertheless, whether it is intraoperative hyperglycemia or increased glucose variability that affects postoperative outcomes is not yet clear. The aim of this study was to assess the association of intraoperative glucose concentration and variability with acute kidney injury (AKI) after cardiac surgery. We retrospectively reviewed the electronic medical records of 3,598 patients who underwent cardiac surgery between November 1, 2006 to December 31, 2016. The time-weighted average glucose (TWAG) and coefficient of variation of glucose measurements were both used as measures of intraoperative glucose control with multivariable logistic regression to evaluate their relationship to postoperative AKI. The intraoperative glucose coefficient of variation was an independent risk factor for AKI after cardiac surgery (highest quartile odds ratio, 1.38; 95% confidence interval, 1.09 to 1.75; P = 0.01). Nevertheless, the intraoperative TWAG did not remain in the final multivariable model of postoperative AKI. Intraoperative glucose variability, but not the average glucose concentration itself, may be a risk factor for AKI after cardiac surgery.

Influence of preoperative hemoglobin A1c on early outcomes in patients with diabetes mellitus undergoing off-pump coronary artery bypass surgery

ObjectiveThere seem to be modifiable components of diabetes in terms of glycemic control to improve surgical outcome. The aim of the study was to evaluate impact of preoperative glycated hemoglobin (HbA1c) level in patients with diabetes mellitus undergoing off-pump coronary bypass (OPCAB) on perioperative glycemic variability and short-term outcome. MethodsMedical records of 703 patients with diabetes mellitus who underwent OPCAB from 2005 to 2017 were reviewed. The perioperative goal of glycemic control was <180 mg/dL. Patients were divided into 2 groups according to HbA1c level (<7.0% or ≥7.0%). Glycemic variability during surgery and up to 24 hours after surgery was assessed by coefficient of variation (CV). Primary outcome was defined as composite of postoperative permanent stroke, prolonged ventilation, deep sternal wound infection, renal failure, reoperation, and 30-day mortality. ResultsIncidence of composite of postoperative morbidity and mortality endpoints was greater in patients with HbA1c ≥7.0% (21% vs 15%, P = .041). Perioperative time-weighted average glucose concentration was also greater in patients with HbA1c ≥7.0%, whereas the CV did not show any difference. Multivariable logistic regression analysis revealed that congestive heart failure, chronic kidney disease, moderate mitral regurgitation or greater, preoperative hemoglobin level, and preoperative HbA1c ≥7.0% were independently associated with composite of postoperative morbidity and mortality, but perioperative CV and time-weighted average glucose ≥200 mg/dL were not. ConclusionsIncreased preoperative HbA1c (≥7.0%) level reflecting long-term glycemic control seems to exert an adverse influence on outcome, whereas the influence of perioperative glycemic variables appear to be abrogated using a target glucose level of <180 mg/dL in patients with diabetes mellitus undergoing OPCAB.

Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications: A Randomized Clinical Trial.

Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery. This dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients. At the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl with standard glycemic management, P < 0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (P < efficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl) occurred in 6 (0.9%) patients. Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

Tight Glycemic Control in Critically Ill Children

BackgroundIn multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking.MethodsIn a 35-center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower-target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher-target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)–free days to day 28.ResultsThe trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower-target group and 353 to the higher-target group. In the intention-to-treat analysis, the median number of ICU-free days did not differ significantly between the lower-target group and the higher-target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per-protocol analyses, the median time-weighted average glucose level was significantly lower in the lower-target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher-target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower-target group also had higher rates of health care–associated infections than those in the higher-target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator-free days.ConclusionsCritically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF-PINT ClinicalTrials.gov number, NCT01565941.)

Intensive insulin therapy: enhanced Model Predictive Control algorithm versus standard care

To investigate the effectiveness of an enhanced software Model Predictive Control (eMPC) algorithm for intravenous insulin infusion, targeted at tight glucose control in critically ill patients, over 72 h, in two intensive care units with different management protocols. Comparison with standard care in a two center open randomized clinical trial. Two adult intensive care units in University Hospitals. Thirty-four critically ill patients with hyperglycaemia (glucose >120 mg/dL) or already receiving insulin infusion. Patients were randomized, within each ICU, to intravenous insulin infusion advised by eMPC algorithm or the ICU's standard insulin infusion administration regimen. Arterial glucose concentration was measured at study entry and when advised by eMPC or measured as part of standard care. Time-weighted average glucose concentrations in patients receiving eMPC advised insulin infusions were similar [104 mg/dL (5.8 mmol/L)] in both ICUs. eMPC advised glucose measurement interval was significantly different between ICUs (1.1 vs. 1.8 h, P < 0.01). The standard care insulin algorithms resulted in significantly different time-weighted average glucose concentrations between ICUs [128 vs. 99 mg/dL (7.1 vs. 5.5 mmol/L), P < 0.01]. In this feasibility study the eMPC algorithm provided similar, effective and safe tight glucose control over 72 h in critically ill patients in two different ICUs. Further development is required to reduce glucose sampling interval while maintaining a low risk of hypoglycaemia.