In accordance with previous studies, this study confirmed the deleterious effect of abnormal glucose metabolism on poor prognosis and early neurological outcomes[5, 12]. Compared with normal glycemic, prediabetes and diabetic with poor PGC appears to be two high risk states of abnormal glucose metabolism. The prediabetes is defined as an intermediate state between normal glucose metabolism and DM, represent growing risks of developing diabetes[6]. Therefore, it is reasonable to suggest that prediabetes and diabetes affect post-thrombolysis early neurological outcomes in same directions. Moreover, the results of this study further confirmed the effect of pre-stroke PGC on the outcome evaluation.
According to the results of this study, diabetic patients with poor PGC had significantly higher admission blood glucose level than other groups, therefore, we considered that the underlying mechanisms may involve the deleterious effects of hyperglycemia. Firstly, hyperglycemia has direct toxic to the ischemic tissue by promoting development of cortical acidosis and associates with worsening mitochondrial function in ischemic penumbra, and further leads to recruitment of ischemic penumbra into infarction[16]. Second, patients with DM and hyperglycemia exhibit procoagulant and prothrombotic properties after AIS[17], in our research, the level of fibrinogen is higher in prediabetes and DM with poor PGC groups. The plasma factor VIIa (FVIIa) which were reported to contributed to enhanced blood coagulation after ischemic stroke by stimulating thrombin generation inducing fibrin deposition, platelet aggregation and thrombus formation[18]. The FVIIa levels were higher in diabetic patients than non-diabetic ischemic stroke patients, and the evaluations were persisted over time[17]. In addition, hyperglycemia and hyperinsulinemia can decrease the fibrinolytic activity by increasing the production of plasminogen activator inhibitor, further affects the activity of rt-PA and impaired recanalization after AIS[19]. Hyperglycemia also affects endothelium-dependent vasodilatation, reduce reperfusion in ischemic brain tissue and increase infarct volumes[20, 21]. Third, hyperglycemia is associated with increased reperfusion injury. Glucose was identified as requisite electron donor for reperfusion-induced neuronal superoxide production [22]. The formation of superoxide further leads to oxidative stress, increased oxidative stress can ultimately lead to neuron death and exacerbate ischemic brain injury[22]. Finally, the insulin resistance could also be involved in the mechanisms. Previous studies have confirmed that insulin resistance is independently associated with poor functional outcome after AIS[23]. The plausible explanations are insulin resistance may lead to proinflammatory and prothrombotic state[24, 25], these effects may further contribute to exacerbate ischemic damage in the brain and affect the response to intravenous thrombolysis[26]. High rates of insulin resistance were found in NIDDM and hypertriglyceridemia and in the low-HDL cholesterol states[27]. In our study, AIS patients with DM have a significantly higher hypertriglyceridemia, especially those with poor PGC. Low-HDL cholesterol states was common in patients with prediabetes and DM.
However, after adjusted for admission hyperglycemia, DM with poor PGC and prediabetes were remains to be an independent significant predictor of no post-thrombolysis ENI. Other factor could also be involved in this mechanism. Previous study have showed that glycemic fluctuation may occurred frequently in prediabetic patients, and the rapid glycemic fluctuation increase the production of oxidative stress and reactive oxygen species, indicating a high risk of END after AIS[28]. Pre-stroke medications may also contribute to the post-thrombolysis early neurological outcomes, in this study we found the prior use of antiplatelet is higher in diabetic patients with good PGC, in another study statin use was also reported to be significantly lower in prediabetic patients than in diabetic patients[6]. Absence of medication and lifestyle management may be a common problem in prediabetic patients and diabetic patients with poor PGC. The acute blood pressure level was associated with END after ischemic stroke[29], our results showed that diastolic blood pressure is significantly higher in prediabetic patients. Although, various factors may be involved, prediabetes and DM with poor PGC still had a significant impact on post-thrombolysis ENI even after adjustment for possible confounders.
The present study has several potential limitations that should be addressed when interpreting the results. First, this is a retrospective study; approximately one-fifth of the patients were excluded because they lacked HbAlc values, and we excluded patients treated with endovascular therapy after IV-rtPA, which inevitably produced biases. Second this study did not complete pre-stroke medication information, especially the use of hypoglycemic drug. Third, this study was performed in a single country, which might limit the generalizability of the results to other patient cohorts. However, the strengths of this study include the large sample size and the fact that patients were selected from multiple centers via strict inclusion and exclusion criteria. This study used HbAlc levels to identified patients with prediabetes, which can be unaffected by the acute-phase reaction[14].