Aim of this study was to investigate the effect of DM on collateral circulation in patients with unilateral MCA severe stenosis or occlusion. Therefore, we compared MRP parameters between diabetic and non-diabetic patients. We found that diabetic patients had better collateral circulation compared with non-diabetic patients, and this kind of impact was independent correlation with DM.
Perfusion techniques provide functional and circulatory information on collateral flow[14]. Numerous studies have addressed the possibility of obtaining information on collateral circulation using MR perfusion. Some investigators have used perfusion measures like the time to maximum of the residue function (Tmax), relative cerebral blood flow (rCBF ) and relative cerebral blood volume (rCBV), assuming that the severity of hypoperfusion in large artery stenosis is directly related to the abundance of collateral vessels[15–18].
Previous studies have explored the relationship between diabetes and collateral circulation with inconsistent conclusions. Some studies have suggests there is no association between diabetes and the extent of pial collaterals in ischemic stroke patients[19]. Menon et al. analyzed patients with AIS treated with intravenous thrombolysis (IVT), mechanical thrombectomy (MT), or basic care and found no association of the blood glucose level and the collateralization [5, 7]. A small study published by Gersing et al. did not find a difference of collateral status between DM patient and NDM patient receiving MT [6]. However, Jan et al. showed that the prevalent elevated glucose levels showed a significant association with the collateral status in the diabetic subgroup [20]. Rosso C et al. shows that collateralization and infarct core did not differ between DM patient and DM patient group, whereas the penumbra was significantly smaller in DM patient than in DM patient [21, 22]. Bin et al shown that greater extent of collateral (more than one-third of the MCA distribution) was detect in DM patents with moyamoya disease. It may means that DM could promote pial collateral vessel formation in patients with chronic cerebral ischemia[23], which is consistent with our findings. Our study shows that in patients with severe stenosis or occlusion of MCA, the ipsilateral collateral circulation of DM patients is more abundant than NDM.
Although presence of a chronic totally occluded lesion has been considered as a prerequisite for spontaneous collateral recruitment, the mechanism of collateral vessel growth is complex, and even becomes more complicated by the presence of DM in which multiple biochemical and cellular components are involved[10, 24–26]. Continuous exposure to hyperglycemia, oxidative stress and increased systemic inflammation factors might induce many changes in the vascular that might accelerate vascular stenosis [27]. The effect of diabetes on collateral supply varies among different organ systems leadings to either impaired or excessive neovascularization. For example, research has shown that DM is associated with reduced coronary collateralization[28]. Excessive angiogenesis occurs in the retina while impaired angiogenesis occurs in the peripheral vasculature[19, 29–31].
The mechanism of neovascularization affected by DM in various organs remains unclear. Through, some study showed angiogenesis was deficient in diabetes groups after ischemic [32, 33]. Li et al. have confirmed that angiogenesis and arteriogenesis showed remarkable increases in the number of collaterals, the diameters of the collaterals, the number of anastomoses, and microvessel density in DM Goto-Kakizaki rats[34]. Similar to this conclusion, Mostafa et al. provide evidence that even after a short duration of relatively mild hyperglycemia, there are structural changes in the cerebral vessels still exist[35]. Some experimental results also revealed a significant rise in the level of vascular endothelial growth factor (VEGF) and nitrotyrosine[36]. Diabetic rats had augmented neovascularization. Both angiogenesis and arteriogenesis were observe, suggesting the adaptive mechanisms are capillary sprouting and remodeling of native collaterals into functional arterioles[19]. The levels of growth factors and cytokines that were regarded as important in the collateral vessels, such as the expression of VEGF, basic fibroblast growth factor, transforming growth factor, granulocyte colony-stimulating factor, and hepatocyte growth factor. It also have been proven be elevated in many studies in intracranial and extracranial artery stenosis disease patients [2, 4, 37, 38]. Angiogenesis is a complex procedure involving many positive and negative regulators. The expression of growth factors and cytokines described above might be higher in MCA stenosis patients complicated with DM than in patients without DM. Thus, more formation regarding collateral angiogenesis can be detected in MCA severe stenosis or occlusion patients with DM.
In this study, we compared the collateral supply among diabetic and nondiabetic patients through MR perfusion parameters, which is confirming that there was more frequently collateral formation of patients with severe stenosis or occlusion of MCA in the DM group. We recognize that there are several limitations have founded in this study. First, a potential weakness of our study is the small sample (especially the number of patients with DM was low). All the potential confound factors could not be controlled, and some influential factors were not taken into account. However, this also provides us with a different point of view and larger sample studies are need to further supports our research results. Second, Markers of longstanding poorly controlled diabetes such as hemoglobin A1C levels, FBG were available of these patients. Duration of diabetes and diabetic control may have varied considerably among patients and contributed of differences in MR perfusion data. Third, we studied the relationship between MR perfusion parameters and collateral circulation, and did not further follow-up and evaluate the risk of late strokes, which will be our next research direction.