The Interaction of Acute and Chronic Glycemia on the Relationship of Hyperglycemia, Hypoglycemia, and Glucose Variability to Mortality in the Critically Ill*

Abstract

Objectives: To determine the relationship between preadmission glycemia, reflected by hemoglobin A1c level, glucose metrics, and mortality in critically ill patients. Design: Retrospective cohort investigation. Setting: University affiliated adult medical-surgical ICU. Patients: The investigation included 5,567 critically ill patients with four or more blood glucose tests and hemoglobin A1c level admitted between October 11, 2011 and November 30, 2019. The target blood glucose level was 90–120 mg/dL for patients admitted before September 14, 2014 (n = 1,614) and 80–140 mg/dL or 110–160 mg/dL for patients with hemoglobin A1c less than 7% or greater than or equal to 7% (n = 3,953), respectively, subsequently. Interventions: None. Measurements and Main Results: Patients were stratified by hemoglobin A1c: less than 6.5.(n = 4,406), 6.5–7.9% (n = 711), and greater than or equal to 8.0% (n = 450). Increasing hemoglobin A1c levels were associated with significant increases in mean glycemia, glucose variability, as measured by coefficient of variation, and hypoglycemia (p for trend < 0.0001, < 0.0001, and 0.0010, respectively). Among patients with hemoglobin A1c less than 6.5%, mortality increased as mean glycemia increased; however, among patients with hemoglobin A1c greater than or equal to 8.0%, the opposite relationship was observed (p for trend < 0.0001 and 0.0027, respectively). Increasing glucose variability was independently associated with increasing mortality only among patients with hemoglobin A1c less than 6.5%. Hypoglycemia was independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% and 6.5–7.9% but not among those with hemoglobin A1c greater than or equal to 8.0%. Mean blood glucose 140–180 and greater than or equal to 180 mg/dL were independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% (p < 0.0001 for each). Among patients with hemoglobin A1c greater than or equal to 8.0% treated in the second era, mean blood glucose greater than or equal to 180 mg/dL was independently associated with decreased risk of mortality (p = 0.0358). Conclusions: Preadmission glycemia, reflected by hemoglobin A1c obtained at the onset of ICU admission, has a significant effect on the relationship of ICU glycemia to mortality. The different responses to increasing mean glycemia support a personalized approach to glucose control practices in the ICU.

Impaired Glucose-Insulin Metabolism in Multisystem Inflammatory Syndrome Related to SARS-CoV-2 in Children

“…Hyperglycemia is not a physiological or benign condition; clinically, hyperglycemia has been linked to increased incidences of sepsis, longer hospital stays and higher mortality [ 39 , 40 , 41 ]. A continuous glucose monitoring may be useful to detect glycemic fluctuation and to prevent metabolic imbalance.…”

Blood glucose-related indicators are associated with in-hospital mortality in critically ill patients with acute pancreatitis

“…According to some studies, transient stress hyperglycemia in critically ill patients is considered harmless, indicating that the body has normal immune regulation capabilities 5 ; nonetheless, fluctuations in blood glucose are considered to cause irreversible organ damage and affect patient prognosis 6 , 7 . However, there are no blood glucose-related indicators for the clinical treatment of patients with AP.…”

The goal of personalized glucose control in the critically ill remains elusive

“…Indeed, although subsequent single-center RCTs confirmed benefit [2,3], multicenter RCTs were largely neutral [4], and the NICE-SUGAR RCT [5] demonstrated increased mortality with tight glucose control, which the investigators attributed to an increased incidence of moderate and severe hypoglycemia [6]. Although these opposing results may be explained by numerous factors including differences in BG target, accuracy of BG measurements, and feeding strategies, emerging evidence from observational and sequential-period studies suggests that the ideal BG target may depend on the pre-existing level of glucose control as reflected by glycated haemoglobin (HbA1c) at ICU admission, whereby patients with 'inadequately controlled' diabetes may benefit from maintaining BG at greater concentrations than those that are optimal or normal for critically ill patients with no or 'well-controlled' diabetes [7][8][9][10]. Sustained hyperglycemia may decrease expression and function of GLUT1 and GLUT4 transporters [11], potentially increasing vulnerability to absolute, or even relative hypoglycemia, i.e.…”

“…Severe hypoglycemia (< 40 mg/dL [< 2.2 mmol/L]) was not statistically different between group (3.9% vs. 2.5%, p = 0.09) but hypoglycemia (defined in this study as BG < 72 mg/dL [< 4 mmol/L]) was more frequent with the intervention (31.2% vs. 15.8%, p < 0.0001). Notably, in cases of severe insulin resistance, the algorithm dictated to continue relatively large insulin doses unless BG decreased below 63 mg/dL [3.5 mmol/L], a level independently associated with mortality in several interventional and observational studies [7,9,14]. Also in the CONTROLING study, moderate and severe hypoglycemia were associated with significantly increased mortality.…”

“…Also in the CONTROLING study, moderate and severe hypoglycemia were associated with significantly increased mortality. While harm of short-lasting hypoglycemia may be context-dependent [9,15], prolonged, recurrent or severe hypoglycemia should be prevented. It should therefore be recognized that the protocol used in this trial recommended to repeat BG one hour after a hypoglycemia episode, which may not prevent prolonged hypoglycemia.…”