高血糖对急性缺血性卒中早期预后影响的初步研究

目的 探讨高血糖对急性缺血性卒中早期预后的影响。方法 采用前瞻性研究设计,连续纳入发病72h内入院的急性缺血性卒中患者143例。急诊入院时检测入院随机静脉血清血糖,高血糖定义为入院随机静脉血清血糖≥7.2mmol/L。入院时评定美国国立卫生研究院卒中量表（NIH Stroke Scale,NIHSS）评分,根据病史及辅助检查确定缺血性卒中类型（TOAST分型）。发病30d时进行改良Rankin’s评分（mRS）,作为评估早期预后的指标。结果 （1）本研究入选的143例急性缺血性卒中患者中,85例（59.4%）出现高血糖,单因素分析显示,年龄、糖尿病史、NIHSS评分是急性缺血性卒中合并高血糖的危险因素（P＜0.05）,logistic回归分析显示,糖尿病史、NIHSS评分是急性缺血性卒中合并高血糖的独立危险因素（P＜0.05）。（2）单因素分析显示,年龄、感染、高血糖、NIHSS评分和TOAST分型对mRS评分的影响有统计学差异（P＜0.05）,logistic回归分析显示,高血糖、NIHSS评分是预后不良的独立危险因素（P＜0.05）。结论 高血糖在急性缺血性卒中患者中的发生率较高,其出现与卒中的严重程度密切相关,可以作为反映急性缺血性卒中发病时病情较重的指标之一,高血糖是急性缺血性卒中早期预后不良的独立危险因素。     

高血糖影响缺血性卒中预后的潜在机制与对策

高血糖增加急性缺血性卒中的死亡率和致残率。目前对于急性缺血性卒中高血糖的控制目标仍无共识。本文对缺血性卒中急性期高血糖的发生机制以及其对预后影响的潜在机制进行了综述,并总结和讨论了近期国内外相关协会有关急性卒中高血糖的处理建议和对策。     

高血糖对急性脑卒中预后的影响

１６３例急性脑卒中患者分为三组：糖尿病组２４例，非糖尿病高血糖组４３例和非糖尿病正常血糖组９６例。按照卒中病人临床神经功能缺损程度评分法和缺血性脑卒中ＣＴ扫描病灶范围评分法，对照分析了卒中后高血糖症与临床表现及脑缺血性损害程度与短期预后的关系。结果表明，急性脑卒中后高血糖不仅临床表现病情重（Ｐ＜０．０１）和脑缺血性损害范围大（Ｐ＜０．０５），而且对卒中短期预后也有不良的影响。     

缺血性卒中急性期血糖水平对卒中病情和预后的影响

目的 探讨急性缺血性卒中患者血糖水平变化与临床病情严重程度以及预后的关系。方法 按入院次日清晨血糖水平,将196例急性缺血性卒中患者分成血糖升高组49例,血糖正常组147例,观察血糖与梗死部位、病灶大小、病情程度以及预后的关系。结果 高血糖的发生与急性缺血性卒中患者病灶部位、临床病情严重程度以及梗死病灶的大小有关,高血糖多见于大脑中线部位梗死及临床症状严重的缺血性卒中患者。血糖升高组患者预后明显差于血糖正常组。结论 高血糖可能加剧急性缺血性卒中患者神经系统损伤,血糖水平的高低可作为判断病情轻重和预后的重要参数。     

卒中急性期应激性高血糖的甄别与处理

临床流行病学研究已证实,糖代谢异常是缺血性卒中的独立危险因素,高血糖对卒中的预后有显著的不良影响,可使其致残率和死亡率明显上升^[1-2]。数十年来,许多学者对于卒中后高血糖发生及其导致卒中预后不良的机制进行了不懈的探索。2型糖尿病占糖尿病的95％左右,但由于2型糖尿病的高度异质性和隐匿性,     

“缺血性卒中/短暂性脑缺血发作血糖管理”的历史、现实和未来——“缺血性卒中/短暂性脑缺血发作血糖管理的中国专家共识”解读之中外指南的比较

本期发表的文章从不同角度对"缺血性卒中/短暂性脑缺血发作(TIA)血糖管理的中国专家共识"进行解读。目前国内外指南对卒中血糖管理的推荐意见不尽相同,特别是最近发表的几个大型临床试验,如ACCORD、ADVANCE、VADT以及UKPDS的后10年研究等,这些临床研究在血糖控制达标值等问题上也莫衷一是,以致使不少医生无所适从。"缺血性卒中/短暂性脑缺血发作血糖管理的历史、现实和未来"一文对中外指南的差异进行了比较,这有助于读者了解不同指南的观点及"中国专家共识"出台的背景和意义。"中国专家共识"首次明确提出:应对既往无糖代谢异常(包括糖尿病和糖尿病前期)病史的缺血性卒中/TIA患者常规行OGTT检查,以避免仅依靠空腹血糖筛查,而漏诊糖耐量异常(IGT)及单纯负荷后高血糖(IPH)患者。"餐后高血糖与卒中"和"糖耐量异常与卒中"2篇文章进一步阐述了上述建议的依据和重要性。"控制高血糖防治卒中的临床研究"一文比较全面地介绍了有关的主要临床研究。虽然流行病学研究已证实血糖增高是卒中的独立危险因子,但迄今临床试验仍未证实严格的控制高血糖可以减少卒中发生的风险。这些临床试验所提供的循证依据有助于我们更好地理解"中国专家共识"中控制高血糖防治卒中的推荐意见。此外,"卒中的血糖管理"一文进一步说明了"中国专家共识"提出的"REACH"原则。贺茂林     

高血糖与卒中预后的关系

卒中合并血糖升高是常见的临床现象,约2/3的急性缺血性卒中患者入院时合并高血糖或患有糖尿病。近年来,越来越多的证据支持高血糖或糖尿病是卒中患者预后不良的独立危险因素,且急性卒中时发生高血糖也是患者预后不良的危险因素。令人遗憾的是,目前国际研究表明,急性期应用胰岛素降糖治疗不能改善高血糖卒中患者预后。到底是由于治疗策略的不当还是试验设计的缺陷,目前尚不清楚。不管是什么原因,都意味着我们对于血糖与卒中的理解仍停留在一个非常粗浅的阶段。由此可见,在卒中领域的血糖管理方面存在许多亟需解决的问题：卒中急性期高血糖/糖尿病如何干预？控制血糖的时间窗是多少？血糖升高到什么水平会导致卒中患者预后不良？用什么样的策略进行血糖干预最合适？干预的强度如何？卒中急性期过后的血糖管理又该遵循怎样的原则？诸多问题都需要我们在临床工作中进行观察和总结,更需要利用循征医学的正确方法进行研究和讨论,只有这样,才能更全面的了解血糖与卒中的关系,以期通过合理的血糖管理策略改善卒中患者的预后。     

血糖水平正常是否可以降低成年急性卒中患者的死亡率和致残率

1文献检索为了证实缺血性卒中(IS)患者血糖水平正常时对卒中预后的影响,根据研究检索策略共筛选两个分别发表于2004年和1999年的平行随机对照试验(RCF,见表1)。以往的研究已经证实:卒中后高血糖与卒中患者预后不良相关,侣还不清楚这是否只是     

编者按：高血糖与卒中

卒中合并血糖升高是常见的临床现象,约2/3的急性缺血性卒中患者入院时合并高血糖或患有糖尿病。近年来,越来越多的证据支持高血糖或糖尿病是卒中患者预后不良的独立危险因素,且急性卒中时发生高血糖也是患者预后不良的危险因素。令人遗憾的是,目前国际研究表明,急性期应用胰岛素降糖治疗不能改善高血糖卒中患者预后。到底是由于治疗策略的不当还是试验设计的缺陷,目前尚不清楚。不管是什么原因,都意味着我们对于血糖与卒中的理解仍停留在一个非常粗浅的阶段。由此可见,在卒中领域的血糖管理方面存在许多亟需解决的问题：卒中急性期高血糖/糖尿病如何干预？控制血糖的时间窗是多少？血糖升高到什么水平会导致卒中患者预后不良？用什么样的策略进行血糖干预最合适？干预的强度如何？卒中急性期过后的血糖管理又该遵循怎样的原则？诸多问题都需要我们在临床工作中进行观察和总结,更需要利用循征医学的正确方法进行研究和讨论,只有这样,才能更全面的了解血糖与卒中的关系,以期通过合理的血糖管理策略改善卒中患者的预后。     

糖尿病糖代谢控制标准与临床治疗策略

目前针对糖尿病与脑血管疾病的研究较少且不系统,尚无法清晰地揭示糖尿病与脑血管病之间的内在联系,但这些有限的资料仍拓宽了对此领域认识的视野,诸如:脂肪源的激素和细胞因子瘦素、抵抗素、脂联素和TNF-α等通过胰岛素抵抗的多种途径参与了脑血管疾病的发生发展;UKPDS研究显示糖化血红蛋白水平的升高确实与缺血性卒中发病有关;代谢综合征和2型糖尿病发生发展的主要原因胰岛素抵抗,已成为高血糖症、高血压、高脂血症、炎性细胞因子产生和血管内皮损伤等的共同土壤,也是缺血性卒中的病理生理基础和危险因素。尽管糖代谢严格控制后对缺血性卒中的防治是否有益仍未达成共识,但越来越多的资料显示出强化控制血糖可使缺血性卒中有减少的趋势。由于糖尿病具有较强的异质性,其脑内中、小血管并发症的成因比微血管并发症更为复杂,当多种危险因素共同存在时,高血糖症对缺血性卒中的影响往往被低估,进行有关糖尿病与脑血管疾病的多中心临床医学研究将可能对许多有争议问题作出解释。神经内科医生与内分泌科医生如若联合起来共同回答上述问题,将可能会完善或充实"卒中单元"的内容,促进糖尿病与脑血管病交叉研究领域的快速发展。     

Hypertension and hyperglycemia in experimental stroke.

Both diabetes mellitus and hypertension are risk factors for stroke and also influence prognosis following stroke. Experimentally, hyperglycemia augments cortical infarct size in stroke models where collateral circulation exists, and infarct size in hypertensive rats is larger than in normotensive strains. Whether the deleterious effect of hyperglycemia is altered in the setting of hypertension has not previously been studied experimentally. The effect of hyperglycemia on infarct size in spontaneously hypertensive rats was examined in this study. Focal neocortical cerebral ischemia was induced by tandem right common carotid and middle cerebral artery occlusion. Preischemic hyperglycemia had no influence on infarct volume whether the duration of postischemic hyperglycemia was transient or prolonged. Although hyperglycemia increases infarct size in cortical stroke models where collateral circulation is available, this study demonstrates the effect can be modified by the presence of underlying hypertension.     

卒中后高血糖与缺血性脑卒中

20～40％的脑卒中患者,无论其此前是否诊断为糖尿病,均可在卒中发生后出现高血糖,称为卒中后高血糖（post stroke hyperglycemia,PSH）。PSH是脑卒中预后的一个重要预测因子,PSH能预测脑卒中患者的死亡风险及神经功能恢复情况。     

The role of hyperglycemia in acute stroke

BACKGROUND: Ischemic stroke is a leading cause of death and long-term disability, and hyperglycemia is believed to aggravate cerebral ischemia. OBJECTIVES: To review animal and human studies on the relationship between hyperglycemia and brain ischemia that elucidate some of the mechanisms for the deleterious effect of hyperglycemia. To discuss present and future clinical recommendations for glucose control. METHODS: Computerized data sources and published indexes and articles from 1976 through 2000 were searched for human studies that evaluated the association between stroke and hyperglycemia, and studies focused on experimental models of hyperglycemic animals with focal and global brain ischemia. RESULTS: Most human studies have shown that in acute stroke, admission hyperglycemia in patients with or without diabetes is associated with a worse clinical outcome than in patients without hyperglycemia. This association is more consistent in the nonlacunar type of stroke. Animal studies support these findings by showing both in global and in focal postischemic models that hyperglycemia exaggerates the following damaging processes: intracellular acidosis, accumulation of extracellular glutamate, brain edema formation, blood-brain barrier disruption, and tendency for hemorrhagic transformation. Insulin treatment of hyperglycemic animals was found to have a beneficial effect in focal and global brain ischemia, which may be mediated by the glucose-reduction effect or by a direct neuroprotection. CONCLUSIONS: Most studies show the deleterious effect of early hyperglycemia, especially in patients with nonlacunar focal or global ischemia. Clinical trials of intensive insulin treatment are needed. Meanwhile simple measures to avoid excessive hyperglycemia are recommended.     

Regional cerebral blood flow decreases during chronic and acute hyperglycemia

The presence of hyperglycemia prior to stroke or cardiac arrest can increase neuronal damage caused by brain ischemia. Acute hyperglycemia shows this effect in animal models of stroke. However, chronic hyperglycemia and chronic hyperglycemia with additional acute elevation of blood glucose are more common premorbid states for stroke patients. The effect of chronic hyperglycemia on regional cerebral blood flow (rCBF) is unclear but blood flow changes may play a role in this ischemic cell damage. We measured rCBF in awake restrained rats that had chronic hyperglycemia induced by treatment with streptozotocin. This was compared to that measured in rats made acutely hyperglycemic by injecting glucose into the peritoneal space. rCBF was measured in 17 brain regions using [14C]iodoantipyrine. During chronic hyperglycemia, when plasma glucose was 29 microns/ml, rCBF was decreased and a regional distribution of this effect was noted; 9 hindbrain regions showed a mean flow decrease of 14% while forebrain regions demonstrated less flow reduction. Acute elevation of plasma glucose during normoglycemia or superimposed on chronic hyperglycemia produced flow reductions of 7% for each 10 microns/ml increment in plasma glucose up to 60 microns/ml. Both chronic and acute hyperglycemia are associated with decreased rCBF and the mechanism for this effect does not appear to adapt to chronic hyperglycemia.     

Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study

Controversy exists whether acute hyperglycemia is causally associated with worse stroke outcome or simply reflects a more severe stroke. In reversible ischemia models, hyperglycemia is associated with lactic acidosis and conversion of penumbral tissue to infarction. However, the relationship between hyperglycemia, lactic acidosis, and stroke outcome has not been explored in humans. Sixty-three acute stroke patients were prospectively evaluated with serial diffusion-weighted and perfusion-weighted magnetic resonance imaging and acute blood glucose measurements. Patients with hypoperfused at-risk tissue were identified by acute perfusion-diffusion lesion mismatch. As a substudy, acute and subacute magnetic resonance spectroscopy was performed in the 33 most recent patients to assess the relationship between acute blood glucose and lactate production in the ischemic region. In 40 of 63 patients with acute perfusion-diffusion mismatch, acute hyperglycemia was correlated with reduced salvage of mismatch tissue from infarction, greater final infarct size, and worse functional outcome. These correlations were independent of baseline stroke severity, lesion size, and diabetic status. Furthermore, higher acute blood glucose in patients with perfusion-diffusion mismatch was associated with greater acute-subacute lactate production, which, in turn, was independently associated with reduced salvage of mismatch tissue. In contrast, acute blood glucose levels in nonmismatch patients did not independently correlate with outcome measures, nor was there any acute-subacute increase in lactate in this group. Acute hyperglycemia increases brain lactate production and facilitates conversion of hypoperfused at-risk tissue into infarction, which may adversely affect stroke outcome. These findings support the need for randomized controlled trials of aggressive glycemic control in acute stroke.     

急性缺血性卒中与血糖波动关系的研究进展

30%～40%急性期脑梗死患者存在应激性高血糖现象,并且与患者尤其是非糖尿病患者
的不良预后相关。强化降糖并未改善这类患者的预后,反而会增加低血糖发生风险。血糖波动是指
血糖在波峰波谷间的波动状态,其可以通过氧化应激和炎症反应导致血管内皮细胞凋亡,而急性期
脑梗死患者出现应激性高血糖可能是血糖波动的一种表象,未来需要更深入的研究。     

Association of non‐diabetic hyperglycemia with autonomic shift in acute ischaemic stroke

Background and purpose: The etiology of hyperglycemia in acute stroke remains controversial. It is unclear whether hyperglycemia arises as an epiphenomenon of stroke or as a reflection of underlying diabetes. Autonomic shift to sympathetic overactivity has been repeatedly observed in acute stroke. We hypothesize that hyperglycemia in acute stroke relates to autonomic imbalance and that the respective deleterious effects on stroke outcome may be cross‐linked. Methods: A total of 75 non‐diabetic patients with ischaemic stroke were included in a prospective study. Glucose levels at admission, fasting glucose, and glucose profiles were recorded. Autonomic function was quantified by the assessment of spontaneous baroreflex sensitivity (BRS) using a cross‐correlation method. Demographic and clinical data including stroke volumes and admission National Institute of Heath Stroke Scale scores were included into the analysis. Functional outcome at 90 days was assessed using the modified Rankin Scale. Results: Hyperglycemia was correlated with decreased BRS independent of stroke severity or volume (r = ?0.46, P < 0.001). In two separate regression models, glucose levels and BRS independently predicted unfavorable outcome at 3 months (OR = 1.06, CI = 1.02–1.11, P = 0.004 and OR = 0.75, CI = 0.56–0.99, P = 0.04). However, combining the models, only glucose levels (OR = 1.06, CI = 1.02–1.11, P = 0.004) remained independent predictor of outcome at 3 months. Conclusions: We observed an association between hyperglycemia and decreased BRS in non‐diabetic patients, suggesting that hyperglycemic reaction in acute stroke may reflect stroke‐related autonomic changes. Moreover, outcome effects of autonomic changes and hyperglycemia seem to be interdependent, putatively having the sympatho‐vagal imbalance as common underlying mechanism. The possible therapeutic relevance of this finding warrants further studies.     

Targets,Treatments, and Outcomes Updates in Diabetic Stroke

Goal: Due to multiple failures to translate basic research, the need for novel therapeutic targets and strategies is still urgent to save a larger number of the stroke patients' population and to reduce the toxicity of the current stroke therapy. Method: We summarize the most recent, within past 5 years, basic and clinical diabetic stroke research findings. Findings: We aim to examine the most current understanding of stroke and neurovascular unit integrity, especially in presence of hyperglycemia and/or diabetes mellitus. From there, we are comparing the meaningful findings that aim at treating diabetic stroke to see where they differ, where they succeed, and where they open questions for new therapeutic strategies. Conclusion: The need for more clinically effective neuroprotective strategies is still mismatched with the bench side findings.