Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective cohort study

Abstract

Background While time in targeted blood glucose range (TIR) 70–140 mg/dL is a known factor associated with mortality in critically ill patients, it remains unclear whether TIR is associated with 28-day mortality under the glycemic control with a less tight target glucose range of 70–180 mg/dL. We aimed to examine whether TIR 70–180 mg/dL was associated with 28-day mortality. Methods This is a retrospective cohort study using data from a tertiary care center in Japan collected from January 2016 through October 2019. We included adult patients (aged ≥20 years) admitted to the ICU. We excluded patients 1) with diabetic ketoacidosis patients, 2) discharged within 48 hours, 3) with repeated ICU admissions. We calculated TIR 70–180 mg/dL using the measured blood glucose values (≥3 times per day). The primary outcome was 28-day mortality. We examined the association between TIR and 28-day mortality using a logistic regression and Cox proportional hazard models with a stratification by glycosylated hemoglobin (HbA1c) level of 6.5%. Additionally, we repeated the analyses using the TIR category to assess the optimal TIR. For the sensitivity analysis, we repeated the primary analysis using TIR during the first three days from ICU admission. Results Of 1,230 patients, the median age was 72 years, 65% were male, and 250 patients (20%) had HbA1c ≥6.5% on admission. In patients with HbA1c <6.5%, TIR <80% was associated with an increased risk of 28-day mortality, with an adjusted odds ratio (OR) of 1.88 (95%CI: 1.36–2.61). Likewise, when using 10% incremental TIR as a categorical variable, lower TIR was associated with a worse 28-day mortality compared with TIR ≥90% (e.g., adjusted OR of TIR <60%, 3.62 [95%CI 2.36–5.53]). Similar associations were found in the analyses using Cox proportional hazards model and using TIR during the first three days. By contrast, in patients with HbA1c ≥6.5%, there was no consistent association of TIR with 28-day mortality. Conclusions We found that lower TIR 70–180 mg/dL was associated with a higher 28-day mortality in critically ill patients with HbA1c <6.5%, whereas there was no consistent association in patients with HbA1c ≥6.5%.

Association between time in range of relative normoglycemia and in-hospital mortality in critically ill patients: a single-center retrospective study

“…One of our findings was that the TIR of absolute normoglycemia (70–140 mg/dL) was significantly associated with in-hospital mortality only among patients with A1C < 6.5% but not among those with A1C ≥ 6.5%, which was consistent with previous studies investigating a time in targeted blood glucose range of 70–139 mg/dL 13 or a time in blood glucose range using the more liberal upper limit (180 mg/dL) 14 . Therefore, our results reaffirm that the range of 70–140 mg/dL cannot be a target for all patients, as well as the importance of individual blood glucose targets in accordance with A1C levels.…”

“…Third, we did not consider the presence or absence of diabetes. However, previous studies have shown that A1C has a stronger effect on the relationship between glucose measurements and outcomes than diabetes 13 , 14 . Fourth, we defined relative normoglycemia as measured blood glucose levels in the range of 70–140% of ADAG based on previous studies; however, the external validity of this range has not yet been assessed.…”

“…The primary exposure was the TIR of relative normoglycemia > 80% during the first 72 h after ICU admission (or ICU stay, whichever was shorter). We adopted this 80% threshold based on previous studies 11 – 14 . The secondary exposure was the TIR of absolute normoglycemia > 80% during the first 72 h after ICU admission (or ICU stay, whichever was shorter).…”

“…In addition to the three domains, the time in the targeted blood glucose range is recognized as an essential factor. Previous studies have shown that a time in the targeted blood glucose range between 70 and 140 (or 180) mg/dL greater than 80% was associated with decreased mortality and other favorable outcomes 11 – 14 . Furthermore, the association between the time in the targeted blood glucose range and mortality was also reported to be dependent on pre-morbid glycemic status, indicating that the positive effects of a longer time in the targeted blood glucose range on mortality were not found in critically ill patients with poor antecedent glycemic control 11 , 13 , 14 .…”

“…Previous studies have shown that a time in the targeted blood glucose range between 70 and 140 (or 180) mg/dL greater than 80% was associated with decreased mortality and other favorable outcomes 11 – 14 . Furthermore, the association between the time in the targeted blood glucose range and mortality was also reported to be dependent on pre-morbid glycemic status, indicating that the positive effects of a longer time in the targeted blood glucose range on mortality were not found in critically ill patients with poor antecedent glycemic control 11 , 13 , 14 . These findings suggest that the optimal blood glucose range needs to be tailored to each patient and provide a rationale for investigating the time in the targeted blood glucose range according to the antecedent glycemic control of individual patients.…”