Range of glucose as a glycemic variability and 3–month outcome in diabetic patients with acute ischemic stroke

RESEARCH ARTICLE Range of glucose as a glycemic variability and 3–month outcome in diabetic patients with acute ischemic stroke Young Seo Kim1, Chulho Kim2*, Keun-Hwa Jung3, Hyung-Min Kwon4, Sung Hyuk Heo5, Beom Joon Kim6, Young Dae Kim7, Jeong-Min Kim8, Seung-Hoon Lee3 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Neurology, Hanyang University School of Medicine, Seoul, Republic of Korea, 2 Department of Neurology, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea, 3 Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea, 4 Department of Neurology, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea, 5 Department of Neurology, Kyung Hee University School of Medicine, Seoul, Republic of Korea, 6 Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea, 7 Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea, 8 Department of Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea * OPEN ACCESS Citation: Kim YS, Kim C, Jung K-H, Kwon H-M, Heo SH, Kim BJ, et al. (2017) Range of glucose as a glycemic variability and 3–month outcome in diabetic patients with acute ischemic stroke. PLoS ONE 12(9): e0183894. https://doi.org/10.1371/ journal.pone.0183894 Editor: Xiaoying Wang, Massachusetts General Hospital, UNITED STATES Received: December 25, 2016 Accepted: August 14, 2017 Published: September 7, 2017 Copyright: © 2017 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: The data set underlying this study is restricted from being made publicly available by the Chuncheon Sacred Heart Hospital Institutional Review Board and Ethics Committee. Interested and qualified researchers may send data requests to Kim Chulho at the following email address: . Funding: The present study was supported by research grants from the Hallym University Specialization Fund (HRF-S-53) and from the Cerebrovascular Research Society Fund (2015-01). Abstract Glycemic variability (GV) is reportedly a predictor for poor outcome in various clinical conditions. We aimed to assess whether GV during hospital admission is associated with poor outcomes in patients with acute ischemic stroke (AIS) and diabetes. We prospectively enrolled consecutive patients with AIS from the registry of 6 tertiary hospitals between January 2013 and December 2014. For the GV index, we used a glucose level range that was divided into 4 quartiles. Multivariable binary and ordinal logistic regression analyses were performed to determine the association between GV and the modified Rankin Scale score (3–6) at 3 months. We enrolled 1,504 patients with AIS and diabetes (mean age, 68.1 years; male, 57.2%), of which 35.1% had poor outcomes at 3 months. An increasing glucose range quartile was positively associated with initial neurologic severity and development of hypoglycemia during hospital admission. Multivariable analysis showed that the glucose level range quartile was associated with poor outcomes, even after adjusting for the number of glucose measurement and hypoglycemia (odds ratio [OR] Q2 vs. Q1: 1.50, 95% confidence interval [CI]: 1.02–2.18; OR Q3 vs. Q1: 2.01, 95% CI: 1.34–3.01; OR Q4 vs. Q1: 1.98, 95% CI: 1.22–3.23). These associations remained significant after dichotomization according to glycated hemoglobin levels at admission. An increasing glucose level range as a GV index during hospital admission was associated with poor functional outcomes at 3 months in patients with AIS and diabetes. Introduction Diabetes is associated with increased risks and worse prognosis in cases with acute ischemic stroke (AIS) [1,2]. Patients with hyperglycemia at admission and during hospitalization, which PLOS ONE | https://doi.org/10.1371/journal.pone.0183894 September 7, 2017 1 / 13 Glycemic variability and outcome after acute ischemic stroke The funders had no role in the study design, data collection and analysis, decision to publish, or preparation for the manuscript. Competing interests: The authors have declared that no competing interests exist. is primarily noted among diabetic patients, are more likely to have worse clinical outcomes as compared to those with normoglycemia [3–5]. Hyperglycemia has a deleterious effect in cases of cerebral ischemia due to increased oxidative stress [6], inflammation [7], apoptosis [8], and inhibition of fibrinolysis [9]. However, the beneficial effects of intensive glucose lowering on the clinical outcomes after AIS remain unclear. In the Diabetes Control and Complications Trial, a reduction in the glycated hemoglobin (A1c) levels was associated with a decreased incidence and progression of microvascular complications in patients with diabetes [10]. However, the observation of a higher risk of retinopathy progression in the conventional treatment group than in the intensive treatment group with similar A1c levels suggests that glycemic variability (GV) could potentially be linked to the development of diabetic complications [11]. Increased fluctuation of blood glucose levels is reported to be associated with poor outcomes in critically ill patients [12,13]. Although several studies have suggested that the nervous system is vulnerable to glycemic excursion [14,15], the role of GV in the outcomes of patients with AIS remains unclear. Therefore, we hypothesized that high GV would be associated with poor functional outcomes in patients with AIS, irrespective of the presence of hyper- or hypoglycemia. In the present study, we aimed to evaluate the association between GV and functional prognosis in patients with diabetes after AIS. Materials and methods Study design and participants We enrolled patients with AIS from 6 tertiary teaching hospitals who were admitted within 7 days of symptom onset, from January 2013 to December 2014. Of 4,376 patients with AIS, we excluded 2,729 who were not diagnosed with diabetes, as glucose measurements during admission alone were not sufficient to indicate glycemic excursion in the usual clinical settings. Moreover, we excluded patients who underwent glucose measurement less than 5 times during admission (n = 132) and those with missing laboratory data (n = 11) (Fig 1). Written Informed consent was obtained from all the patients or the authorized next of kin, and the institutional review board (IRB) and ethics committee of each participating hospital (IRBs in Hanyang University Hospital, Chuncheon Sacred Heart Hospital, Seoul National University Hospital, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Kyung Hee University Hospital and Seoul Nationa (...truncated)