Introduction
Stroke is the second most common cause of death and the leading cause of disability in adults worldwide [1]. Stroke can be divided into transient ischemic attack (TIA), ischemic stroke (IS), hemorrhagic stroke (HS), and subarachnoid hemorrhage. Acute IS (AIS) can have serious lifelong consequences [2]. Since stroke is considered a disease caused by long-term exposure to lifestyle-related risk factors, modification of these risk factors has a significant impact on stroke incidence and the level of stroke-related disability [3]. Risk factors for thrombotic AIS include modifiable (gender, age, ethnicity, and race) and non-modifiable (hypertension, dyslipidemia, diabetes mellitus, and smoking) risk factors [3, 4]. 
Intravenous (IV) or subcutaneous (SQ) insulin injection is the mainstay of treatment for blood sugar control after stroke in the acute phase [11, 12]. However, little evidence has been reported on which method of administration is better [13]. In a trial comparing IV and SQ insulin injections to manage hyperglycemia in post-stroke patients, IV insulin therapy had a better effect on lowering blood glucose by increasing the risk of controllable hypoglycemic events [14]. Given the lack of evidence in this field and the importance of managing hyperglycemia in patients with AIS, we aimed to investigate blood sugar fluctuations after IV and SQ insulin injections in diabetic patients with AIS.

Methods
This cross-sectional analytical study was conducted on 242 diabetic patients admitted to the emergency department of Poursina Hospital in Rasht, Iran, due to AIS and received IV thrombolysis. Their AIS diagnosis was confirmed by computed tomography (CT) scan. They were selected using a gradual sampling method from among 570 patients. Inclusion criteria were age over 18 years, type 2 diabetes, AIS diagnosis, and hospital admission within 12 hours of symptom onset. Exclusion criteria were the presence of cerebral hemorrhagic events associated with AIS, pregnancy, admission to the intensive care unit before the incidence of AIS, diabetic ketoacidosis, and hyperosmolar hyperglycemia. The choice of insulin injection method was based on the patients’ clinical conditions. Patients with a baseline blood sugar of more than 180 mg/dL were placed on a regular SQ or IV insulin therapy protocol. Those with blood sugar less than 60 mg/dL who were at risk of hypoglycemia had their insulin treatment discontinued and underwent an injection of 50 ml of 50% dextrose intravenously. To compare demographic characteristics such as age, gender, duration of diabetes, and some underlying diseases in the two groups treated with IV and SQ insulin protocols, independent t-test and chi-square test were used. One-way repeated measures analysis of variance (ANOVA) was used to determine the trend in blood sugar changes over time and based on groups. Using analysis of covariance, the relationship between factors affecting blood sugar levels in patients was examined by eliminating the effect of blood sugar at admission. The data analysis was conducted in SPSS software, version 20. P<0.05 was considered statistically significant.

Results
The frequency of hyperlipidemia in patients in the IV insulin group was significantly higher than in the SQ insulin group (P=0.027). Also, the frequency of hypertension in patients in the IV insulin group was higher than in the SQ insulin group, and this difference was in the borderline of statistical significance (P=0.055).

Blood sugar changes from the time of admission to 24 hours after admission
In between-group comparisons, the mean blood sugar levels between the two groups at the time of admission and 6 and 12 hours after admission were significantly different (P<0.001 and P=0.016), where the IV insulin group had significantly higher blood sugar levels than the SQ insulin group. However, there was no significant difference in the mean blood sugar level 18 hours and 24 hours after admission between the two groups (P>0.05). Within both groups, a significant reduction in blood sugar was observed over time. Pairwise comparisons showed that this difference was statistically significant between the times of admission and 6 hours, between 6 and 12 hours, and between 12 and 18 hours after admission, but no significant difference was observed between 18 and 24 hours after admission.

Comparison of hypokalemia and duration of glycemic control in the first 24 hours
A significant difference was observed in the frequency of hypokalemia between the two groups. It was significantly higher in the IV insulin group than in the SQ insulin group (P=0.007). Also, the average duration of glycemic control in the first 24 hours in the SQ group was significantly lower than in the IV group (P<0.001).

Comparison of the effects of insulin administration protocols on hypoglycemia 
There was no significant difference between the effectiveness of IV and SQ protocols in reducing hypoglycemia when the average initial blood sugar was 241-300 mg/dL. By the increase in the initial blood sugar level above 300 mg, the rate of hypoglycemia reduction by the IV method was significantly greater than by the SQ method. The rate of hypoglycemia reduction in the IV insulin injection group was significantly higher in all three groups of patients with initial blood sugar levels of 301-350 mg (P=0.023), 351-400 mg (P=0.002) and >400 mg (P=0.001) compared to the SQ injection group.

Factors affecting blood sugar levels in the first 24 hours
A significant relationship was observed between the type of insulin administration and glycemic control during the first 24 hours in patients (P<0.001). Factors such as hypoglycemia at admission (P<0.001), hypertension (P=0.007) and age (P=0.036) also showed a positive and significant association with blood sugar levels in patients in the first 24 hours. In other words, increasing age and hypertension were associated with increased blood sugar levels in the first 24 hours.

Conclusion
In diabetic patients with AIS receiving insulin by the IV method, the initial blood sugar level is significantly higher than in those receiving insulin by the SQ method. This is one of the factors that influences the therapist’s decision to select a treatment regimen based on the patient’s clinical condition to reduce the complications of AIS and to select thrombolysis treatment at the appropriate time.

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the Ethics Committee of Guilan University of Medical Sciences, Rasht, Iran (Code: IR.GUMS.REC.1397.508).

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Conceptualization and validation: Seyyed Mahdi Zia Ziabari, Behrang Motamed, Babak Bakhshayesh Eghbali, Nazanin Noori Roodsari, and Yasman Kamiar; Methodology: Seyyed Mahdi Zia Ziabari, Nazanin Noori Roodsari, Yasman Kamiar, and Mohammad Ali Yazdanipour; Investigation: Seyyed Mahdi Zia Ziabari, Behrang Motamed, Babak Bakhshayesh Eghbali, Nazanin Noori Roodsari, and Yasman Kamiar; Writing the original draft: Nazanin Noori Roodsari, Yasman Kamiar, Ashkan Asgari Gesht Rudkhani, and Mohammad Ali Yazdanipour; Review and editing: All author; Supervision, Seyyed Mahdi Zia Ziabari, Behrang Motamed, Babak Bakhshayesh Eghbali, and Nazanin Noori Roodsari.

Conflicts of interest
The authors declared that there are no conflicts of interest in this article.

Acknowledgements
The authors express their gratitude to the Office of Education Development, Porsina Medical Sciences and the Neuroscience Research Center, Guilan University of Medical Sciences, Rasht, Iran. 


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