Augmented Glycemic Gap is a Marker for Predicting the Early Neurological Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

Research Article

Austin Neurol & Neurosci. 2023; 6(1): 1029.

Augmented Glycemic Gap is a Marker for Predicting the Early Neurological Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

Ling Wang1#; Nuo Wang1#; Ting Hu2#; Haiyan Liu2; Tao Wu3*; Qiantao Cheng4*

1Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China

2Department of Neurology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

3Center of Cerebrovascular Disorders, Department of Neurology, Second Military Medical University, Shanghai, China

4Department of Neurology, Huai’an 82 hospital, Jiangsu, China

#These authors have contributed equally to this article.

*Corresponding author: Tao Wu Center of Cerebrovascular Disorders, Department of Neurology, Second Military Medical University, Shanghai, China; Qiantao Cheng, Department of Neurology, Huai’ an Hospital, Jiangsu, China. Tel: (+)86-13391232009; (+)86-13033553377 Email: twu163@163.com; hongtao20030706@126.com

Received: August 23, 2023 Accepted: September 21, 2023 Published: September 28, 2023

Abstract

Background and Purpose: Glycemic Gap (GG) as an index reflecting the acute fluctuation of glycemia, has been proved to be associated with poor functional outcomes in Acute Ischemic Stroke (AIS) patients. However, it predictive value on post-thrombolysis Early Neurological Outcomes (ENOs) are still controversial. This study aimed to use GG to evaluate the influence of pretreatment relative glucose changes on post-thrombolysis ENOs, and we further explored the predictive value of GG in different glycemic control status.

Methods: Early Neurological Deterioration (END) was defined as a National Institutes of Health Stroke Scale Score (NIHSS) =4, Early Neurological Improvement (ENI) was defined as a =4-point decrease in NIHSS score or a complete resolution of neurological deficits, between the time of admission and 24 hours after intravenous recombinant tissue-type plasminogen activator (IV-rtPA). GG was calculated as Admission Blood Glucose level (ABG)- estimated average blood glucose level (eAG), eAG could be derived from HbAlc according to the equation eAG=28.7*HbAlc-46.7

Results: Increased GG was significantly associated with post-thrombolysis END and poor functional outcome at discharge (OR, 1.982; 95% CI, 1.213-3.238; P=0.006) (OR, 2.079; 95% CI, 1.305-3.312; P=0.002). Its predictive value on END was more pronounce in diabetic patients (OR, 2.434; 95% CI, 1.079-5.491; P=0.032), after dichotomizing glycemic control status, its significance was only maintained in diabetic patients with good previous glucose control (OR, 6.946; 95% CI, 1.217-39.636; P=0.029).

Conclusion: An evaluated GG was associated with high risk of post-thrombolysis END and poor functional outcome at discharge in AIS patients, and the previous glucose control should be considered when predicting ENOs.

Keywords: Acute ischemic stroke; Early neurological deterioration; Poor functional outcome; Glycemic gap; Stress induced hyperglycemia

Introduction

Stress-Induced Hyperglycemia (SIH) is a common phenomenon during acute phase of severe illness, it could be a hallmark of diseases severity [1]. SIH controlled background glycemia reflects the fluctuation of glucose in the acute phase of the diseases. The underlying mechanisms involves activation of hypotha-lamic-pituituary-adrenal axis and sympatho-adrenal system, reflects the severity of physiological stress [2]. Glycemia Gap (GG) is a novel index of glycemic excursion to quantifies the relative glycemic rise from chronic glycemia in the acute phase of illness. Previous studies have confirmed that GG is a useful marker for predicting poor outcomes after some critical illness, including ischemic stroke [3-5]. However, the prognostic value of GG requires comprehensive consideration patients previous glucometabolic level. The deleterious effects of increased GG was more pronounce in diabetic patients [6], according to the results of one study, the effect of elevated GG on poor functional outcome was more significant in diabetic patients with good previous glucose control [3].

Early Neurological Deterioration (END) after Acute Ischemic Stroke (AIS) is a prominent clinical issue that is strongly correlated with poor functional outcome and mortality [7,8]. In our previous study, we found that Stress Hyperglycemia Ratio (SHR), which is calculated as Admission Blood Glucose (ABG) level divided by glycosylated hemoglobin (HbAlc %), was significantly associated with END, and this association is more pronounced in diabetic patients [9]. Compared with SHR, the GG was calculated as ABG minus the estimating blood glucose (eAG) determined by HbAlc [10], reflecting the absolute difference from eAG [11]. The predictive value of GG on END is unclear. Therefore, the aim of this study was to validate its predictive value on Early Neurological Outcomes (ENO), and we further explored the whether the predictive effects is different in AIS patients with different previous glucose metabolism.

Method

Study Population

This study retrospectively included consecutive patients with AIS treated with intravenous recombinant tissue-type plasminogen activator (IV-rtPA) at the Department of Neurology, Center of Cerebrovascular Disorders, ChangHai Hospital and Department of Neurology, The Second Affiliated Hospital of Xu Zhou Medical School from January 2017, to December 2020. Patients enrolled in this study if they: (1) aged 18 years or older; (2) were admission within 4.5h after onset; and (3) were treatment with IV-rtPA. Patients were excluded from this study if they: (1) were diagnoses of malignant tumors, autoimmune diseases, major organ failure or presence of an active infection; and (2) had incomplete clinical data. We further excluded patients treated with IV-rtPA and endovascular thrombectomy to maintain the homogeneity of the enrolled patients. Written informed consent was obtained from participants or legal representatives. The study protocol was approved by Ethics Committee of ChangHai Hospital and The Second Affiliated Hospital of Xu Zhou Medical School.

Baseline Assessments

Stroke severity was assessed via National Institutes of Health Stroke Scale (NIHSS). The Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria was used to classified stroke subtype [12]. The diagnosis of Symptomatic Intracranial Hemorrhage (sICH) was based on the results of CT scans, combined with a NIHSS score of =4. A poor functional outcome at discharge was defined as a Modified Rankin Scale (mRS) score of 3-6 at discharge. The mRS score were collected the day before discharge by two trained physicians independent of the study. The proximal artery occlusion confirmed by the Computed Tomography Angiography (CTA), Magnetic Resonance Angiography (MRA) and Digital Subtraction Angiography (DSA). Image data were reviewed in blind manner by two physicians, with advice of the third experienced physicians in case of disagreement.

Definition of Post-Thrombolysis Early Neurological Outcome

The post-thrombolysis END was defined as a =4-point increase in NIHSS score between the time of admission and 24 hours after IV-rtPA [13]. Meanwhile post-thrombolysis ENI was defined as a =4-point decrease in NIHSS score or a complete resolution of neurological deficits between the time of admission and 24 hours after IV-rtPA [14,15]. Neurological deficit was evaluated on admission and at 24 hours after IV-rtPA by two certified neurologists blinded to the clinical data.

Assessment of Glycemic Gap

Fasting plasm glucose levels were monitored shortly after admission before IV-rtPA. Glycosylated hemoglobin (HbAlc%) was measured within 24 hours after hospitalization, estimated average blood glucose level (eAG) could be derived from HbAlc according to the equation eAG=28.7*HbAlc-46.7 [10]. GG was calculated as ABG-eAG [11].

Assessment of Abnormal Glucose Metabolism Status

According to the recommended of American Diabetes Association (ADA), DM was diagnosed based on prior history of diabetes or an HbAlc =6.5% and patients with HbAlc less than 5.7% were classified as NGM [16]. Diabetic patients were classified into 2 groups according to PGC, diabetic patients with good PGC had HbAlc <7%, diabetic patients with poor PGC had HbAlc =7% [16]. Patients HbAlc was measured within 24 hours after hospitalization. Admission blood glucose was measured shortly after arrived the emergency room, hyperglycemia was defined as blood glucose levels higher than 7.8mmol/L [17].

Statistical Analysis

The Kolmogorov–Smirnov test was performed to test the normality of variables, and continuous variables were described as the mean (standard deviation) and median (quartile) based on the normality of the data. Categorical variables are expressed as percentages. Differences in the baseline characteristics were assessed by Χ² test for categorical variables and ANOVA or Kruskal–Wallis test for continuous variables.

Multivariate logistical regression was performed to analysis the association of GG and early neurological outcome, patients were tertiled according to the GG value, the first tertile group as the reference category. The covariates entered in the multivariable logistical regression were age, gender admission NIHSS, Neutrophil to Lymphocyte Ratio (NLR), time of Onset To Treatment (OTT), proximal artery occlusion, stroke subtype, sICH. The Receiver Operating Characteristic (ROC) curve was used to determine the accuracy of GG in predicting ENOs in AIS patients treated with IV-rtPA, two-tailed P values of <0.05 were considered statistically significant. Data analyses were performed using the statistical software package SPSS 22.0 for Windows (IBM, Armonk, NY).

Results

Baseline Characteristics

A total of 798 AIS patients treated with IV-rtPA were included in this study, 139(17.4%) patients had END, 207(25.9%) patients had ENI and 215(26.9%) patients had poor function outcome. Patients were tertiled according to the GG value, the baseline characteristics were presented in table 1. Patients in the higher GG group were more likely to have higher systolic blood pressure (151 vs. 156 vs.153; P=0.019); to have a higher incidence of large artery atherosclerosis and DM (23.3% vs. 28.6% vs. 36.8%; P=0.041) (37.2% vs. 19.5% vs. 48.1%; P<0.001); to have a higher occurrence of END and poor functional outcome at discharge (13.2% vs. 14.3% vs. 24.8%; P<0.001) (11.7% vs. 16.5% vs. 52.6%; P<0.001); to have a higher level of NLR (2.3 vs. 2.4 vs. 2.8; P<0.001). Patients were less likely to experience post-thrombolysis ENI in the higher GG tertile group (31.2% vs. 26.3% vs. 20.3%; P=0.016).