The association of intravenous insulin and glucose infusion with intensive care unit and hospital mortality: a retrospective study.

BACKGROUND: We assessed the association of intravenous insulin and glucose infusion with intensive care unit (ICU) and hospital mortality. METHODS: For this retrospective association study, we used data from all patients admitted to a medical-surgical ICU between January 2012 and September 2017. We excluded patients admitted < 24 h, patients with a diabetic ketoacidosis, patients with a therapy restriction upon ICU admission and readmissions. Using multivariate logistic regression, we examined the relation between intravenous insulin and glucose infusion and ICU and hospital mortality for all patients. Additionally, we used the same model to analyze the outcomes for patients admitted > 72 h. RESULTS: Of 9507 eligible patients, 3966 were included. After correction for potential confounders, intravenous insulin was associated with ICU and hospital mortality in patients admitted > 24 h (n = 3966) (odds ratio (OR) 1.09 [95% CI 1.05-1.13] and 1.09 [95% CI 1.06-1.13] per 0.1 IU/kg added, respectively). Likewise, intravenous glucose was associated with ICU mortality (OR 1.01 [95% CI 1.00-1.01]) but not with hospital mortality and (OR 1.00 [95% CI 1.00-1.01]) per g/day added, respectively. In patients admitted > 72 h (n = 1550), insulin dose was associated with both ICU and hospital mortality (p = 0.002 and p < 0.001, respectively), but glucose infusion was not (p = 0.08 and p = 0.2, respectively). CONCLUSIONS: Intravenous insulin administration is associated with an increased risk of ICU and hospital mortality, after correction for potential confounders. Parenteral glucose administration was limited in amount but was still associated with ICU mortality. However, based on these results, it is unknown whether this association is an epiphenomenon, or represents a true harm of insulin and glucose administration.

Glycemic Effects of a Low-Carbohydrate Enteral Formula Compared With an Enteral Formula of Standard Composition in Critically Ill Patients: An Open-Label Randomized Controlled Clinical Trial.

BACKGROUND: Enteral low-carbohydrate formulas (LCFs) could serve as a noninsulin alternative for the treatment of stress hyperglycemia in critically ill patients. We compared the glycemic effects of an LCF with a standard formula. METHODS: We conducted an open-label randomized trial in patients admitted to our intensive care unit between September 2015 and June 2016. Adult patients with an indication for enteral nutrition were randomized to an LCF (Glucerna 1.5 kcal) or a standard enteral formula (Fresubin Energy Fibre, with additional protein supplement). Primary outcome was glucose variability defined as mean absolute glucose (MAG) change (mmol/L/h). Secondary outcomes were mean glucose, time in target, hypoglycemic and hyperglycemic events, and insulin requirements. We assessed glycemic outcomes per blinded continuous glucose monitoring (CGM) system and compared outcomes with glucose measurements per blood gas analysis and point-of-care device. RESULTS: We randomized 107 patients (LCF: n = 53; standard: n = 54). Six patients had no CGM data, leaving 101 patients (n = 52; n = 49) for the intention-to-treat analysis. MAG change and time in target range were not different between groups. LCF gave a lower mean glucose measured per point-of-care device (7.8 ± 1.0 vs 8.4 ± 1.1 mmol/L, P = .007). LCF patients required significantly less insulin on the second study day (46.8 vs 68.0 IU, P = .036). CONCLUSION: LCF showed a trend toward a modestly reduced mean glucose and significantly lower insulin requirements as compared with standard feeding but had no effect on glucose variability or time in target range.

Haemoglobin glycation index and risk for diabetes-related complications in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

AIMS/HYPOTHESIS: Previous studies have suggested that the haemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications in individuals with type 1 and type 2 diabetes. We investigated whether HGI was a predictor of adverse outcomes of intensive glucose lowering and of diabetes-related complications in general, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. METHODS: We studied participants in the ADVANCE trial with data available for baseline HbA1c and fasting plasma glucose (FPG) (n = 11,083). HGI is the difference between observed HbA1c and HbA1c predicted from a simple linear regression of HbA1c on FPG. Using Cox regression, we investigated the association between HGI, both categorised and continuous, and adverse outcomes, considering treatment allocation (intensive or standard glucose control) and compared prediction of HGI and HbA1c. RESULTS: Intensive glucose control lowered mortality risk in individuals with high HGI only (HR 0.74 [95% CI 0.61, 0.91]; p = 0.003), while there was no difference in the effect of intensive treatment on mortality in those with high HbA1c. Irrespective of treatment allocation, every SD increase in HGI was associated with a significant risk increase of 14-17% for macrovascular and microvascular disease and mortality. However, when adjusted for identical covariates, HbA1c was a stronger predictor of these outcomes than HGI. CONCLUSIONS/INTERPRETATION: HGI predicts risk for complications in ADVANCE participants, irrespective of treatment allocation, but no better than HbA1c. Individuals with high HGI have a lower risk for mortality when on intensive treatment. Given the discordant results and uncertain relevance beyond HbA1c, clinical use of HGI in type 2 diabetes cannot currently be recommended.

Venous, Arterialized-Venous, or Capillary Glucose Reference Measurements for the Accuracy Assessment of a Continuous Glucose Monitoring System.

BACKGROUND: Different reference methods are used for the accuracy assessment of continuous glucose monitoring (CGM) systems. The effect of using venous, arterialized-venous, or capillary reference measurements on CGM accuracy is unclear. METHODS: We evaluated 21 individuals with type 1 diabetes using a capillary calibrated CGM system. Venous or arterialized-venous reference glucose samples were taken every 15 min at two separate visits and assessed per YSI 2300 STAT Plus. Arterialization was achieved by heated-hand technique. Capillary samples were collected hourly during the venous reference visit. The investigation sequence (venous or arterialized-venous) was randomized. Effectiveness of arterialization was measured by comparing free venous oxygen pressure (PO2) of both visit days. Primary endpoint was the median absolute relative difference (ARD). RESULTS: Median ARD using arterialized-venous reference samples was not different from venous samples (point estimated difference 0.52%, P = 0.181). When comparing the three reference methods, median ARD was also not different over the full glycemic range (venous 9.0% [n = 681], arterialized-venous 8.3% [n = 684], and capillary 8.1% [n = 205], P = 0.216), nor over the separate glucose ranges. Arterialization was successful (PO2 venous 5.4 kPa vs. arterialized-venous 8.9 kPa, P < 0.001). Arterialized-venous glucose was significantly higher than venous glucose and numerically higher than capillary glucose (arterialized-venous 142 mg/dL vs. venous 129 mg/dL [P < 0.001] and vs. capillary 134 mg/dL [P = 0.231]). Inconvenience related to arterialization included transient mild edema and redness of the hand in 4 out of 21 (19%) patients. CONCLUSIONS: The use of venous, arterialized-venous, or capillary reference measurements did not significantly impact CGM accuracy. Venous reference seems preferable due to its ease of operation.

The Clinical Benefits and Accuracy of Continuous Glucose Monitoring Systems in Critically Ill Patients-A Systematic Scoping Review.

Continuous Glucose Monitoring (CGM) systems could improve glycemic control in critically ill patients. We aimed to identify the evidence on the clinical benefits and accuracy of CGM systems in these patients. For this, we performed a systematic search in Ovid MEDLINE, from inception to 26 July 2016. Outcomes were efficacy, accuracy, safety, workload and costs. Our search retrieved 356 articles, of which 37 were included. Randomized controlled trials on efficacy were scarce (n = 5) and show methodological limitations. CGM with automated insulin infusion improved time in target and mean glucose in one trial and two trials showed a decrease in hypoglycemic episodes and time in hypoglycemia. Thirty-two articles assessed accuracy, which was overall moderate to good, the latter mainly with intravascular devices. Accuracy in critically ill children seemed lower than in adults. Adverse events were rare. One study investigated the effect on workload and cost, and showed a significant reduction in both. In conclusion, studies on the efficacy and accuracy were heterogeneous and difficult to compare. There was no consistent clinical benefit in the small number of studies available. Overall accuracy was moderate to good with some intravascular devices. CGM systems seemed however safe, and might positively affect workload and costs.

Higher glucose variability in type 1 than in type 2 diabetes patients admitted to the intensive care unit: A retrospective cohort study.

PURPOSE: Although the course of disease of type 1 and type 2 diabetes differs, the distinction is rarely made when patients are admitted to the intensive care unit (ICU). Here, we report patient- and admission-related characteristics in relation to glycemic measures of patients with type 1 and type 2 diabetes admitted to the ICU. MATERIALS AND METHODS: A retrospective chart review was performed of 1574 patients with diabetes admitted between 2004 and 2011 to our ICU. Glycemic measures included mean glucose, the incidence of hypoglycemia and hyperglycemia, percentage of glucose values in/below/above target, and glucose variability. The ICU and hospital mortality were secondary outcomes. RESULTS: We classified 2% (n=27) of patients as having type 1 diabetes and 98% (n=1547) as having type 2 diabetes. Patients with type 1 diabetes were significantly younger, had a lower body mass index, and were more frequently admitted to the ICU for medical diagnoses. No differences in glycemic measures were found, apart from a 20% higher glucose variability in the type 1 diabetes group. CONCLUSIONS: Patients with type 1 diabetes showed a higher glucose variability, but overall glycemic control was not different between patients with type 1 and type 2 diabetes. Very few diabetes patients admitted to the ICU have type 1 diabetes.