The Synergistic Effect of Chronic Hyperglycemia and Dehydration on the Progression of Cerebral Infarction

Keywords

Dehydration; Chronic hyperglycemia; Infarct core; Bun/Cr; HbA1c; Infarct progression.

Abstract

Background : Studies on the role of chronic hyperglycemia and dehydration in the progression of acute cerebral infarction have confirmed that chronic hyperglycemia can promote the progression of acute cerebral infarction, and dehydration can also accelerate the development of cerebral infarction. However, there are few studies on the co-effects of chronic hyperglycemia and dehydration on infarct core volume. Since it is not uncommon for stroke patients to have chronic hyperglycemia and dehydration at the same time, it is of certain clinical significance to study the interaction of the two on stroke. Method: A total of 270 patients with acute cerebral infarction were included and admitted to hospital to improve the examination of glycosylated hemoglobin, blood urea nitrogen and blood creatinine. We would use blood urea nitrogen (BUN)/creatinine (Cr) ratio as a dehydration marker.The dehydrated group was defined as the blood urea nitrogen/creatinine ratio >15, and the non dehydrated group was defined as the blood urea nitrogen/creatinine ratio ≤15. HbA1c >7% was defined as chronic hyperglycemia group, HbA1c ≤7% was defined as non-chronic hyperglycemia group. According to the above definition, they were divided into four groups: dehydration + chronic hyperglycemia group, dehydration + non-chronic hyperglycemia group, non-dehydration + chronic hyperglycemia group, and non-dehydration + non-chronic hyperglycemia group. At the same time, the magnetic resonance DWI examination was improved, the infarct core volume was processed by the software after the acute cerebral infarction magnetic resonance image, and the correlation between the infarct core volume and glycosylated hemoglobin and blood urea/creatinine ratio was evaluated. hyperglycemia group. Results: The core volume of cerebral infarction in chronic hyperglycemia group was larger (infarct volume >43.28ml, HBA1c IQR 6.5%). The core volume of cerebral infarction in dehydrated group was larger (infarct volume >43.28ml, BUN/Cr IQR 17.632). The core volume of cerebral infarction was the largest in dehydration + chronic hyperglycemia group, followed by dehydration + non-chronic hyperglycemia group, non-dehydration + chronic hyperglycemia group, and non-dehydration + non-chronic Conclusion: Chronic hyperglycemia in patients with acute cerebral infarction is likely to lead to dehydration, which is the main reason for the enlargement of the infarct core. Therefore, it is possible for patients with chronic hyperglycemia to avoid the expansion of the infarct core by correcting the key link of critical dehydration.

Abstract

Background : Studies on the role of chronic hyperglycemia and dehydration in the progression of acute cerebral infarction have confirmed that chronic hyperglycemia can promote the progression of acute cerebral infarction, and dehydration can also accelerate the development of cerebral infarction. However, there are few studies on the co-effects of chronic hyperglycemia and dehydration on infarct core volume. Since it is not uncommon for stroke patients to have chronic hyperglycemia and dehydration at the same time, it is of certain clinical significance to study the interaction of the two on stroke. Method: A total of 270 patients with acute cerebral infarction were included and admitted to hospital to improve the examination of glycosylated hemoglobin, blood urea nitrogen and blood creatinine. We would use blood urea nitrogen (BUN)/creatinine (Cr) ratio as a dehydration marker.The dehydrated group was defined as the blood urea nitrogen/creatinine ratio >15, and the non dehydrated group was defined as the blood urea nitrogen/creatinine ratio ≤15. HbA1c >7% was defined as chronic hyperglycemia group, HbA1c ≤7% was defined as non-chronic hyperglycemia group. According to the above definition, they were divided into four groups: dehydration + chronic hyperglycemia group, dehydration + non-chronic hyperglycemia group, non-dehydration + chronic hyperglycemia group, and non-dehydration + non-chronic hyperglycemia group. At the same time, the magnetic resonance DWI examination was improved, the infarct core volume was processed by the software after the acute cerebral infarction magnetic resonance image, and the correlation between the infarct core volume and glycosylated hemoglobin and blood urea/creatinine ratio was evaluated. hyperglycemia group. Results: The core volume of cerebral infarction in chronic hyperglycemia group was larger (infarct volume >43.28ml, HBA1c IQR 6.5%). The core volume of cerebral infarction in dehydrated group was larger (infarct volume >43.28ml, BUN/Cr IQR 17.632). The core volume of cerebral infarction was the largest in dehydration + chronic hyperglycemia group, followed by dehydration + non-chronic hyperglycemia group, non-dehydration + chronic hyperglycemia group, and non-dehydration + non-chronic Conclusion: Chronic hyperglycemia in patients with acute cerebral infarction is likely to lead to dehydration, which is the main reason for the enlargement of the infarct core. Therefore, it is possible for patients with chronic hyperglycemia to avoid the expansion of the infarct core by correcting the key link of critical dehydration.

Keywords

Dehydration; Chronic hyperglycemia; Infarct core; Bun/Cr; HbA1c; Infarct progression.

Citation

Huanyin (2026) The Synergistic Effect of Chronic Hyperglycemia and Dehydration on the Progression of Cerebral Infarction. SM J Clin Med Imaging 8: 7.

INTRODUCTION

Cerebral infarction, also known as ischemic stroke, is one of the most common acute cerebrovascular diseases in our clinic. It is caused by various reasons, the local blood supply disorder of brain tissue, the appearance of brain tissue ischemia and hypoxia, and then produce clinical corresponding neurological deficits. In the clinical process, it is often encountered that a patient’s condition continues to progress and aggravates 3 to 5 days after the onset of the disease [1]. These continuously aggravated neurological deficits often take doctors by surprise and make many patients and their families express that they cannot understand, which is easy to cause medical disputes. So, what factors are related to the progression of cerebral infarction? [2]. If we can have a means to judge the progress of cerebral infarction, it will bring great benefits to the doctor. However, there is no uniform international guidelines and consensus on progressive stroke. We have previously found that hyperglycemia may be a very important factor in the progression of cerebral infarction [3], or systemic dehydration of patients leads to cerebral hypoperfusion [4], which leads to the aggravation of cerebral infarction. But how does a brain infarction progress? What is its pathogenesis? We don’t know much, and the growth of infarct size is a complex and dynamic process [5]. There’s a lot of variation between patients, and we don’t have any way of assessing how the size of a patient’s infarct increases [6]. For example, is the progression of infarction due to the necrosis of brain tissue caused by ischemia-reperfusion injury? Or is it the poor quality of the collateral circulation of the cerebral artery that leads to the progression of cerebral infarction? Or is it due to the age of the patient and poor control of basal blood pressure? Or is it because of the level of blood sugar? All of these factors can influence the outcome of infarction, and we do not know if one of these factors is dominant or if they are combined. Therefore, we still need to further explore the specific factors affecting the progression of cerebral infarction.Our previous studies have shown that chronic hyperglycemia has a certain influence on the prognosis of acute cerebral infarction [7]. At the same time, many people use blood glucose levels to predict poor outcomes of stroke, but how blood glucose affects the development of cerebral infarct size is still controversial. Chronic hyperglycemia, the patient’s glycated hemoglobin level, reflects the patient’s blood glucose level in the 3 months before the onset of the disease, and is associated with the prognosis of cerebral infarction. We have also found that in clinical patients, if dehydration is present, cerebral infarction is progressive [8]. In these dehydrated patients, we can stop the progression of infarction and improve neurological function by rehydration or by enhancing volume expansion. So, are there patients with chronic hyperglycemia, which is due to the presence of dehydration, that is, because of high blood glucose, leading to cell dehydration, which aggravates the deterioration of brain function, leading to an increase in the area of cerebral infarction? Diffusion weighted imaging (DWI) [9], in magnetic resonance imaging is the only noninvasive method that can detect the diffusion motion of water molecules in living tissues. After cerebral infarction, cells produce toxic edema that restricts the diffusion of water molecules. Therefore, DWI can detect high-signal images within a few minutes after cerebral infarction, and the size of this image can be used to evaluate the size of the patient’s cerebral infarction area. After cerebral infarction, there is local hemodynamic impairment around the infarct core [10], and without effective intervention, the extent of the impairment will spread spatially over time. The infarct core may then spread to nearby tissue, causing irreversible damage to the healthy tissue surrounding the infarct [11]. As a result, the area surrounding the high signal on DWI can be transformed into a infarct. Therefore, in clinical practice, can we calculate the core volume of cerebral infarction through DWI examination, and then calculate the dehydration and glycosylated hemoglobin to evaluate the prognosis of patients with cerebral infarction?

MATERIAL AND METHODS

We included 270 hospitalized patients with acute cerebral infarction within 24 hours of onset between 2019 and 2021 [Table 1]. The exclusion criteria wererenal insufficiency (creatinine > 1.5 mg/dl), malignant tumor, no informed consent, or without blood samples. The study was approved by the ethics committee of Minhang Hospital, Fudan University. All patients or their family members or legal representatives provided written informed consent after being informed of the study protocol. Demographic and clinical data were collected on admission, including demographic data (age, sex, body mass index [BMI]), vascular risk factors (smoking status, alcohol abuse, hypertension, diabetes mellitus, hypercholesterolemia, atrial fibrillation, coronary heart disease, a history of stroke, medication history (antithrombotic use, statin use, antihypertensive agent, anticoagulant, anti-glycemic agent), laboratory parameters (BUN/Cr, HbA1c), and other biochemical variables(high sensitivity C-reactive protein, Homocysteine, fasting blood glucose, low density lipoprotein cholesterol, triglycerides etc), were measured using routine laboratory methods on the second day after admission. All patients underwent 3.0T MRI scans within 24 hours of admission (uMR780; United Imaging Healthcare; Shanghai, China, with a commercial 24-channel head-and-neck coil). The stroke region obtained from DWI images was manually segmented on the graphical user interface of MATLAB software. In order to improve the segmentation accuracy, the DWI image is filtered in advance. The lesion area was then identified and sectioned by two experienced neuroradiologists. Finally, the segmentation results are fused with the original DWI image and displayed to check whether the segmentation results are accurate. All patients admitted to hospital were given a National Institutes of Health Scale (NIHSS) score by an experienced neurologist. The ratio of creatinine to urea nitrogen was calculated. If the ratio was greater than 15, it indicated that the patient was dehydrated. If the ratio was less than 15, it indicated that the patient was not dehydrated. HbA1c >7% was defined as chronic hyperglycemia, HbA1c ≤7% was defined as non-chronic hyperglycemia.

Table 1: Baseline characteristics by levels of Bun/Cr Ratio in acute ischemic stroke.

IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale. *P value for difference between dehydration and normal hydration group, using chi-square for percentages and Kruskal-Wallis test for medians.

The average age of the 270 patients included was 65 years old (56-73), among which 126 were females (46.7%) and 144 were males (53.3%). The average BMI (kg/m2, IQR) of these patients was 26.8(25.5 27.3). Vascular risk factors included: hypertension in 176 cases (64.8%), diabetes mellitus in 106 cases (39.3%), coronary heart disease in 76 cases (28.1%), hypercholesterolemia in 85 cases (31.5%), atrial fibrillation in 38 cases (14.1%), transient ischemic attack in 45 cases (16.7%). There were 56 smoking patients, accounting for 20.7%. Pre-stroke treatment included 145 patients receiving antithrombotic therapy (53.7%) and 84 patients receiving statin therapy (31.1%). In the acute stage of cerebral infarction, 58 patients (21.5%) received r-TPA thrombolytic therapy. The mean NIH score of all 270 patients before admission was 7 (4-12), and the mean volume of cerebral infarction was 5.32 mm3 (1; 67-14.77), The average time from the onset of cerebral infarction to the hospital was 5.1 hours, and the mean time from admission to MRI completion was 7.5 hours. Etiological classification of stroke included: 80 cases of cardiogenic embolism, accounting for 29.6%, 68 cases of small artery occlusion, accounting for 25.2%, 67 cases of large atherosclerosis, accounting for 24.8%, 32 cases of other causes, accounting for 11.9%, 23 cases of unknown cause, accounting for 8.5%. Laboratory results indicated that the mean value of high-sensitive C-reactive protein was 0.42mg/ml, the mean value of homocysteine was 19.2umol/l, the mean value of rapid blood sugar was 5.48mmol/l, and the mean value of brain-derived neurotrophic factor was 22.1ng/ml.

STATISTICAL ANALYSIS

Continuous data are summarized as a median (interquartile range [IQR]), and categorical variables are presented as a number (percent) of subjects. The Kruskal-Wallis test and chi-square test were used to compare the two groups. Bivariate correlations were analyzed using Spearman’s Rank correlation considering the abnormal distribution of data. Binary logistic regression analysis was used to adjust for possible confounding factors. Furthermore, a semiparametric approach with univariate and multivariate quartile regression analysis was used to evaluate the relationship between median NIHSS score and DWI infarct volume quartiles. Results were expressed as adjusted odds ratios (OR) with the corresponding 95% confidence interval (CI). All statistical analysis was performed with R language (https://www.r-project.org/)as a processing environment. Statistical significance was defined as P < 0.05. 

RESULTS

The Relationship between infarct volume and NIHSS score [Figure 1 + Table 2] Q1 indicates small infarct volume, BUN/Cr is 13.935, NIHSS score is less than 5 points, Q2 infarct volume is larger than Q1, BUN/Cr is 14.016, NIHSS score is greater than 5 points, Q3 infarct volume is larger than Q2, BUN/Cr is 15.57, greater than 15, NIHSS score is greater than Q2 score. Q4 had the largest infarct volume, the BUN/Cr was 17.632, and the NIHSS score was much higher than 10 points. From the above comparison, it can be found that the size of the infarct was positively correlated with the NIHSS score, and the larger the infarct size, the higher the NIHSS score. we also adopted univariate and multivariate quartile regression models to estimate stroke severity for infarct volumes quartiles. Other data included age, sex, BMI, risk factors, clinical information, and treatment prior to stroke.

Figure 1: Infarct severity (NIHSS score) was correlated with infarct volume.

The relationship between infarct volume and glycosylated hemoglobin [Figure 2 and Table 3].

When the HbA1c IQR is 6%, the infarct volume is less than 0.907ml; when the HbA1c IQR is 6.3%, the infarct volume is between 0.907 and 3.16ml; when the HbA1c IQR is 6.5%, the infarct volume is greater than 43.28ml, indicating that the higher the HbA1c is, the larger the infarct volume is. In patients with large infarct volume, the interquart interval of HbA1c was 6.5%, indicating that the core volume of infarction was correlated with chronic hyperglycemia (HbA1c) , possible confounders: sex, age, BMI, risk factors, clinical information (including time from onset, the biochemical examination, and MR imaging) [Table 3, Figure 2].

The relationship between glycosylated hemoglobin and dehydration

There is no dehydration, that is, the BUN/Cr ratio is less than 15, the HbA1c IQR is 6%, there is dehydration, the BUN/Cr ratio is greater than 15, the HbA1c IQR is 6.5%, indicating that the dehydrated patients have higher HbA1c. [Table 4, Figure 3,Figure 4].

DISCUSSION

Cerebral infarction is due to the sudden decrease or stop of the blood flow in the local blood supply artery of the brain tissue, resulting in the necrosis and softening of the brain tissue caused by cerebral ischemia and hypoxia in the blood supply area of the blood vessel, and accompanied by the clinical symptoms and signs of the corresponding parts [12]. In clinic, most of the symptoms are hemiplegia, slurred speech, disturbance of consciousness, dysphagia and other neurological function loss symptoms. The clinical manifestations of cerebral infarction are varied, and are related to the site of injury, the size of cerebral ischemia vessels, the severity of ischemia, the condition of collateral circulation, and whether there are other diseases complicated [13]. Clinically, some cerebral infarction patients are very mild, even asymptomatic, called 

Figure 4: Relationship between dehydration and chronic hyperglycemi.

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Citation

Huanyin (2026) The Synergistic Effect of Chronic Hyperglycemia and Dehydration on the Progression of Cerebral Infarction. SM J Clin Med Imaging 8: 7.