Correlation of Glycemic Variability and Time in Range with Early Neurological Deterioration in Patients with Acute Ischemic Stroke and Diabetes

doi:10.12114/j.issn.1007-9572.2021.02.133

Chinese General Practice ›› 2022, Vol. 25 ›› Issue (12): 1418-1423.DOI: 10.12114/j.issn.1007-9572.2021.02.133

Special Issue: 内分泌代谢性疾病最新文章合辑；神经系统疾病最新文章合辑；脑健康最新研究合辑

• Original Research • Previous Articles Next Articles

Correlation of Glycemic Variability and Time in Range with Early Neurological Deterioration in Patients with Acute Ischemic Stroke and Diabetes

Department of Neurology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China

Received:2021-09-24 Revised:2021-11-15 Published:2022-01-13 Online:2022-03-21
Contact: Xiaopeng YANG
About author:
WANG M, XI Z, MENG Q Z, et al. Correlation of glycemic variability and time in range with early neurological deterioration in patients with acute ischemic stroke and diabetes [J] . Chinese General Practice, 2022, 25 (12) : 1418-1423.

血糖变异性和葡萄糖目标范围内时间与急性缺血性脑卒中合并糖尿病患者早期神经功能恶化的相关性研究

450003　河南省郑州市，郑州大学第二附属医院神经内科

通讯作者: 杨霄鹏
作者简介:
王铭，奚志，孟启哲，等.血糖变异性和葡萄糖目标范围内时间与急性缺血性脑卒中合并糖尿病患者早期神经功能恶化的相关性研究[J].中国全科医学，2022，25（12）：1418-1423. 作者贡献：王铭提出研究选题方向和总体研究目标，负责设计研究方案及确定研究方法；杨霄鹏对研究进行可行性分析并确定具体实施方案；王铭、奚志、孟启哲负责收集、整理临床资料，提供数据；奚志、孟启哲负责数据分析与统计学处理，并对统计结果进行解释；王铭、奚志负责撰写论文初稿；杨霄鹏负责论文最终稿的修订、论文的质量控制及审校，对论文整体负责，监督管理；所有作者确认了论文的最终稿。
基金资助:
河南省医学科技攻关计划项目(201503089)

Abstract

Abstract:

Background

Early neurological deterioration (END) in acute ischemic stroke is associated with permanent neurological deficits and dysfunction, and considered to be an unstable condition requiring comprehensive medical treatment. Moreover, the relationship between END and glycemic variability (GV) remains unclear.

Objective

To explore the relationship of GV, time in range (TIR) with END in patients with acute ischemic stroke and diabetes, and based on this, to develop a predictive model.

Methods

One hundred and twenty patients with acute ischemic stroke and diabetes (34 with END and 86 without) were selected from the Second Affiliated Hospital of Zhengzhou University from July 2019 to May 2021. Clinical data, GV indices 〔coefficient of variation (CV) , standard deviation (SD) , mean amplitude of glycemic excursion (MAGE) , mean of daily differences (MODD) 〕 and TIR measured by the 72-hour ambulatory continuous glucose monitoring were collected. Factors associated with END were explored by multivariate Logistic regression, and used to develop a nomogram for the prediction of END. ROC analysis was conducted to assess the predictive value of nomogram for END.

Results

Patients with END had higher mean glycosylated hemoglobin (HbA_1c) , admission NIH Stroke Scale score, CV, SD, MAGE, and MODD, and lower mean TIR than did those without (P<0.05) . Multivariate Logistic regression analysis indicated that increased CV〔OR=1.194, 95%CI (1.027, 1.388) , P=0.021〕, SD〔OR=11.040, 95%CI (1.189, 102.473) , P=0.035〕, MAGE〔OR=3.063, 95%CI (1.062, 8.837) , P=0.038〕, and MODD〔OR=20.990, 95%CI (1.420, 201.206) , P=0.027〕 were associated with elevated risk of END, and prolonged TIR〔OR=0.877, 95%CI (0.789, 0.974) , P=0.014〕 was associated with decreased risk of END. Internal validation of the predictive value of nomogram incorporating CV, SD, MAGE, MODD and TIR for END using bootstrapping showed that its predicted value was basically consistent with the actual value, demonstrating good predictive ability. For estimating END in acute ischemic stroke combined with diabetes, the AUC of CV, SD, MAGE, MODD and TIR was 0.847〔95%CI (0.765, 0.929) , P<0.01〕, 0.812〔95%CI (0.723, 0.901) , P<0.01〕, 0.850〔95%CI (0.772, 0.928) , P<0.01〕, 0.803〔95%CI (0.710, 0.896) , P<0.01〕, and 0.825〔95%CI (0.747, 0.903) , P<0.01〕, respectively.

Conclusion

CV, SD, MAGE, MODD and TIR may be influential factors for END in acute ischemic stroke with diabetes, which could partially predict END. It is of clinical significance to take measures to reduce GV and prolong TIR to prevent END.

Key words: Ischemic stroke, Diabetes mellitus, Early neurological deterioration, Blood glucose variability, Time in glucose target range, Nomograms

摘要：

背景

急性缺血性脑卒中早期神经功能恶化（END）与永久性神经缺陷、功能障碍有关，并且被认为是一种不稳定的情况，需要进行全面的内科治疗。而END与血糖波动之间的关系尚不十分清楚。

目的

探索血糖变异性（GV）、葡萄糖目标范围内时间（TIR）与急性缺血性脑卒中合并糖尿病患者发生END的关系并建立预测模型。

方法

选取2019年7月至2021年5月郑州大学第二附属医院收治的急性缺血性脑卒中合并糖尿病患者120例为研究对象，根据是否发生END分为END组（34例）和非END组（86例）。收集患者临床资料并进行72 h动态血糖监测，记录其GV相关指标〔血糖变异系数（CV）、血糖标准差（SD）、24 h平均血糖波动幅度（MAGE）、日间血糖平均绝对差（MODD）〕及葡萄糖TIR。采用多因素Logistic回归分析探究急性缺血性脑卒中合并糖尿病患者发生END的影响因素，并建立列线图预测模型，采用受试者工作特征（ROC）曲线评估预测价值。

结果

END组糖化血红蛋白（HbA_1c）、入院美国国立卫生研究院卒中量表（NIHSS）评分、CV、SD、MAGE、MODD均高于非END组，葡萄糖TIR低于非END组（P<0.05）。多因素Logistic回归分析结果显示，CV〔OR=1.194，95%CI（1.027，1.388），P=0.021〕、SD〔OR=11.040，95%CI（1.189，102.473），P=0.035〕、MAGE〔OR=3.063，95%CI（1.062，8.837），P=0.038〕、MODD〔OR=20.990，95%CI（1.420，201.206），P=0.027〕升高是急性缺血性脑卒中合并糖尿病患者发生END的危险因素，葡萄糖TIR〔OR=0.877，95%CI（0.789，0.974），P=0.014〕升高是急性缺血性脑卒中合并糖尿病患者发生END的保护因素。基于CV、SD、MAGE、MODD及葡萄糖TIR建立急性缺血性脑卒中合并糖尿病患者发生END的列线图预测模型。对该模型采用Bootstrap法进行内部验证，预测值与实际值基本一致，说明该模型具有较好的预测能力。绘制CV、SD、MAGE、MODD及葡萄糖TIR预测急性缺血性脑卒中合并糖尿病患者发生END的ROC曲线，结果显示，CV、SD、MAGE、MODD、葡萄糖TIR预测急性缺血性脑卒中合并糖尿病患者发生END的ROC曲线下面积（AUC）分别为0.847〔95%CI（0.765，0.929），P<0.01〕、0.812〔95%CI（0.723，0.901），P<0.01〕、0.850〔95%CI（0.772，0.928），P<0.01〕、0.803〔95%CI（0.710，0.896），P<0.01〕、0.825〔95%CI（0.747，0.903），P<0.01〕。

结论

CV、SD、MAGE、MODD及葡萄糖TIR可能是急性缺血性脑卒中合并糖尿病患者发生END的影响因素，并对END的发生有一定的预测作用，通过降低GV并增加葡萄糖TIR对预防END发生有一定的临床价值。

关键词: 缺血性卒中, 糖尿病, 早期神经功能恶化, 血糖变异性, 葡萄糖目标范围内时间, 列线图

Ming WANG,Zhi XI,Qizhe MENG, et al. Correlation of Glycemic Variability and Time in Range with Early Neurological Deterioration in Patients with Acute Ischemic Stroke and Diabetes[J]. Chinese General Practice, 2022, 25(12): 1418-1423. DOI: 10.12114/j.issn.1007-9572.2021.02.133.
王铭,奚志,孟启哲等. 血糖变异性和葡萄糖目标范围内时间与急性缺血性脑卒中合并糖尿病患者早期神经功能恶化的相关性研究[J]. 中国全科医学, 2022, 25(12): 1418-1423. DOI: 10.12114/j.issn.1007-9572.2021.02.133.

Figures/Tables 6

References 25

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指标		END组（n=34）	非END组（n=86）	检验统计量值	P值
年龄（±s，岁）		66.6±9.6	65.6±10.6	-0.443	0.659
性别（男/女）		22/12	47/39	1.001^a	0.315
BMI（±s，kg/m²）		23.9±3.0	24.1±2.7	0.387	0.699
吸烟史〔n（%）〕		9（26.47）	26（30.23）	0.167^a	0.683
饮酒史〔n（%）〕		5（14.71）	11（12.79）	0.073^a	0.781
既往病史〔n（%）〕
	高血压	25（73.53）	55（63.95）	1.001^a	0.316
	冠心病	6（17.65）	11（12.79）	0.473^a	0.492
	脑梗死	5（14.71）	9（10.47）	0.425^a	0.514
	高脂血症	20（58.82）	45（52.33）	0.414^a	0.520
糖尿病病程（±s，年）		7.03±3.55	6.47±2.84	-1.276	0.204
治疗方式〔n（%）〕				2.327^a	0.508
	饮食控制	9（26.47）	16（18.60）
	口服降糖药物	16（47.06）	38（44.19）
	皮下注射胰岛素	6（17.65）	26（30.23）
	口服+皮下注射	3（8.82）	6（6.98）
空腹血糖（±s，mmol/L）		14.2±3.8	13.0±3.5	-1.613	0.110
HbA_1c（±s，%）		8.91±1.50	8.17±1.36	2.585	0.011
总胆固醇（±s，mmol/L）		4.64±0.93	4.59±0.92	-0.268	0.790
三酰甘油（±s，mmol/L）		1.49±0.54	1.54±0.57	0.439	0.661
高密度脂蛋白（±s，mmol/L）		0.97±0.26	1.00±0.24	0.623	0.548
低密度脂蛋白（±s，mmol/L）		2.62±0.77	2.70±0.85	0.477	0.635
Hcy（±s，μmol/L）		13.65±4.30	12.24±4.02	-1.698	0.092
入院NIHSS评分〔M（P₂₅，P₇₅），分〕		4.00（2.00，7.00）	2.00（1.00，4.00）	-2.418^b	0.016

指标		END组（n=34）	非END组（n=86）	检验统计量值	P值
年龄（±s，岁）		66.6±9.6	65.6±10.6	-0.443	0.659
性别（男/女）		22/12	47/39	1.001^a	0.315
BMI（±s，kg/m²）		23.9±3.0	24.1±2.7	0.387	0.699
吸烟史〔n（%）〕		9（26.47）	26（30.23）	0.167^a	0.683
饮酒史〔n（%）〕		5（14.71）	11（12.79）	0.073^a	0.781
既往病史〔n（%）〕
	高血压	25（73.53）	55（63.95）	1.001^a	0.316
	冠心病	6（17.65）	11（12.79）	0.473^a	0.492
	脑梗死	5（14.71）	9（10.47）	0.425^a	0.514
	高脂血症	20（58.82）	45（52.33）	0.414^a	0.520
糖尿病病程（±s，年）		7.03±3.55	6.47±2.84	-1.276	0.204
治疗方式〔n（%）〕				2.327^a	0.508
	饮食控制	9（26.47）	16（18.60）
	口服降糖药物	16（47.06）	38（44.19）
	皮下注射胰岛素	6（17.65）	26（30.23）
	口服+皮下注射	3（8.82）	6（6.98）
空腹血糖（±s，mmol/L）		14.2±3.8	13.0±3.5	-1.613	0.110
HbA_1c（±s，%）		8.91±1.50	8.17±1.36	2.585	0.011
总胆固醇（±s，mmol/L）		4.64±0.93	4.59±0.92	-0.268	0.790
三酰甘油（±s，mmol/L）		1.49±0.54	1.54±0.57	0.439	0.661
高密度脂蛋白（±s，mmol/L）		0.97±0.26	1.00±0.24	0.623	0.548
低密度脂蛋白（±s，mmol/L）		2.62±0.77	2.70±0.85	0.477	0.635
Hcy（±s，μmol/L）		13.65±4.30	12.24±4.02	-1.698	0.092
入院NIHSS评分〔M（P₂₅，P₇₅），分〕		4.00（2.00，7.00）	2.00（1.00，4.00）	-2.418^b	0.016

组别	例数	CV（%）	SD（mmol/L）	MAGE（mmol/L）	MODD（mmol/L）	葡萄糖TIR（%）
END组	34	28.97±8.39	2.58±0.39	5.51±0.76	2.09±0.35	43.21±9.05
非END组	86	18.34±5.88	2.11±0.35	4.45±0.73	1.73±0.35	55.51±9.28
t值		7.859	6.423	7.089	5.677	-6.590
P值		<0.001	<0.001	<0.001	<0.001	<0.001

组别	例数	CV（%）	SD（mmol/L）	MAGE（mmol/L）	MODD（mmol/L）	葡萄糖TIR（%）
END组	34	28.97±8.39	2.58±0.39	5.51±0.76	2.09±0.35	43.21±9.05
非END组	86	18.34±5.88	2.11±0.35	4.45±0.73	1.73±0.35	55.51±9.28
t值		7.859	6.423	7.089	5.677	-6.590
P值		<0.001	<0.001	<0.001	<0.001	<0.001

因素	β	SE	Waldχ²值	P值	OR值	95%CI
HbA_1c	0.190	0.282	0.456	0.499	1.210	（0.696，2.102）
NIHSS评分	0.091	0.201	0.205	0.650	1.096	（0.738，1.625）
CV	0.177	0.077	5.341	0.021	1.194	（1.027，1.388）
SD	2.402	1.137	4.463	0.035	11.040	（1.189，102.473）
MAGE	1.119	0.541	4.287	0.038	3.063	（1.062，8.837）
MODD	3.044	1.374	4.908	0.027	20.990	（1.420，201.206）
葡萄糖TIR	-0.132	0.054	5.989	0.014	0.877	（0.789，0.974）

Correlation of Glycemic Variability and Time in Range with Early Neurological Deterioration in Patients with Acute Ischemic Stroke and Diabetes

血糖变异性和葡萄糖目标范围内时间与急性缺血性脑卒中合并糖尿病患者早期神经功能恶化的相关性研究

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