Diabetes mellitus and ischemic stroke: current pathophysiological mechanisms and pharmaceutical research status_West China Medical Journal

Authors：

ZHU chan ^1,2 , ZHANG qiang ³ ,  CHEN qiu ⁴

1. Department of Traditional Chinese Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Key Laboratory of Birth Defects and Related Gynecological Diseases, Sichuan Chengdu, Sichuan 610066, P. R. China;
3. Foot and Ankle Department, Sichuan Province Orthopaedic Hospital, Chengdu, Sichuan 610041, P. R. China;
4. Department of Endocrinology, Hospital of Chengdu University of TCM/ TCM Hospital of Sichuan Province, Chengdu, Sichuan 610072, P. R. China;

Corresponding author：

CHEN qiu, Email: chenqiu1005@cdutcm.edu.cn

Keywords：

Diabetes mellitus; ischemic stroke; mechanisms; pharmaceutical

DOI：

10.7507/1002-0179.202312022

Video：

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Abstract Full text Figures/Tables Video References Cited by

Diabetes mellitus patients have the characteristics of higher morbidity of ischemic stroke, severe symptoms, more recurrent stroke and higher mortality. Current studies have shown that stroke patients with or without diabetes mellitus have different pathophysiological mechanisms during stroke progress. Accordingly, treatment that is beneficial to non-diabetes mellitus patients may not be beneficial to diabetes mellitus stroke patients. This article reviews the current research status of pathophysiological mechanism of diabetes mellitus complicated with ischemic stroke, and provides reference for the relevant research of drug intervention in diabetes mellitus patients complicated with stroke.

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2. Magliano DJ, Boyko EJ; IDF Diabetes Atlas 10th edition scientific committee. IDF diabetes atlas. 10th ed. Brussels: International Diabetes Federation, 2021.
3. 国家心血管病中心. 中国心血管健康与疾病报告 2023. 北京: 中国协和医科大学出版社, 2024.
4. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation, 2012, 125(1): e2-e220.
5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 2019, 50(12): e344-e418.
6. Magwood GS, White BM, Ellis C. Stroke-related disease comorbidity and secondary stroke prevention practices among young stroke survivors. J Neurosci Nurs, 2017, 49(5): 296-301.
7. Emerging Risk Factors Collaboration; Sarwar N, Gao P, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet, 2010, 375(9733): 2215-2222.
8. Lee M, Saver JL, Hong KS, et al. Effect of pre-diabetes on future risk of stroke: meta-analysis. BMJ, 2012, 344: e3564.
9. 张健, 袁戈恒. 糖尿病卒中: 被忽视的大血管并发症. 中华糖尿病杂志, 2020, 12(11): 864-869.
10. Sang H, Liu L, Wang L, et al. Opposite roles of bradykinin B1 and B2 receptors during cerebral ischaemia-reperfusion injury in experimental diabetic rats. Eur J Neurosci, 2016, 43(1): 53-65.
11. Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520, 000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet, 2018, 50(4): 524-537.
12. Njølstad PR, Hertel JK, Søvik O, et al. Progress in diabetes genetics. Tidsskr Nor Laegeforen, 2010, 130(11): 1145-1149.
13. Wang N, Liu Q, Liu H, et al. Association of apolipoprotein E polymorphisms and risks of ischemic stroke in Chinese patients with type 2 diabetes mellitus. J Diabetes Res, 2021, 2021: 8816996.
14. Chiou HY, Bai CH, Lien LM, et al. Interactive effects of a combination of the HDAC3 and HDAC9 genes with diabetes mellitus on the risk of ischemic stroke. Thromb Haemost, 2021, 121(3): 396-404.
15. Zhao B, Yuan Q, Hou JB, et al. Inhibition of HDAC3 ameliorates cerebral ischemia reperfusion injury in diabetic mice in vivo and in vitro. J Diabetes Res, 2019, 2019: 8520856.
16. Wolf V, Abdul Y, Li W, et al. Impact of diabetes and ischemic stroke on the cerebrovasculature: a female perspective. Neurobiol Dis, 2022, 167: 105667.
17. Maida CD, Daidone M, Pacinella G, et al. Diabetes and ischemic stroke: an old and new relationship an overview of the close interaction between these diseases. Int J Mol Sci, 2022, 23(4): 2397.
18. Ramana KV, Chandra D, Srivastava S, et al. Nitric oxide regulates the polyol pathway of glucose metabolism in vascular smooth muscle cells. FASEB J, 2003, 17(3): 417-425.
19. Yang H, Ma S, Liu Y, et al. Poor outcome of experimental ischemic stroke in type 2 diabetic rats: impaired circulating endothelial progenitor cells mobilization. J Stroke Cerebrovasc Dis, 2015, 24(5): 980-987.
20. Ye G, Gao Q, Qi P, et al. The role of diabetes mellitus on the thrombus composition in patients with acute ischemic stroke. Interv Neuroradiol, 2020, 26(3): 329-336.
21. Gao Q, Qi P, Wang J, et al. Effects of diabetes mellitus complicated by admission hyperglycemia on clot histological composition and ultrastructure in patients with acute ischemic stroke. BMC Neurol, 2022, 22(1): 130.
22. Sheikh-Ali M, Chehade JM, Mooradian AD. The antioxidant paradox in diabetes mellitus. Am J Ther, 2011, 18(3): 266-278.
23. Rendra E, Riabov V, Mossel DM, et al. Reactive oxygen species (ROS) in macrophage activation and function in diabetes. Immunobiology, 2019, 224(2): 242-253.
24. Wang GX, Li GR, Wang YD, et al. Characterization of neuronal cell death in normal and diabetic rats following exprimental focal cerebral ischemia. Life Sci, 2001, 69(23): 2801-2810.
25. Zhang HY, Wang ZG, Lu XH, et al. Endoplasmic reticulum stress: relevance and therapeutics in central nervous system diseases. Mol Neurobiol, 2015, 51(3): 1343-1352.
26. Srinivasan K, Sharma SS. Augmentation of endoplasmic reticulum stress in cerebral ischemia/reperfusion injury associated with comorbid type 2 diabetes. Neurol Res, 2011, 33(8): 858-865.
27. Giordano M, Trotta MC, Ciarambino T, et al. Circulating miRNA-195-5p and -451a in diabetic patients with transient and acute ischemic stroke in the emergency department. Int J Mol Sci, 2020, 21(20): 7615.
28. Chen J, Ning R, Zacharek A, et al. MiR-126 contributes to human umbilical cord blood cell-induced neurorestorative effects after stroke in type-2 diabetic mice. Stem Cells, 2016, 34(1): 102-113.
29. Duan X, Zhan Q, Song B, et al. Detection of platelet microRNA expression in patients with diabetes mellitus with or without ischemic stroke. J Diabetes Complications, 2014, 28(5): 705-710.
30. Karam RA, Amer MM, Zidan HE. Long noncoding RNA NEAT1 expression and its target miR-124 in diabetic ischemic stroke patients. Genet Test Mol Biomarkers, 2022, 26(7/8): 398-407.
31. Lontchi-Yimagou E, Sobngwi E, Matsha TE, et al. Diabetes mellitus and inflammation. Curr Diab Rep, 2013, 13(3): 435-444.
32. Przykaza Ł. Understanding the connection between common stroke comorbidities, their associated inflammation, and the course of the cerebral ischemia/reperfusion cascade. Front Immunol, 2021, 12: 782569.
33. Panés J, Kurose I, Rodriguez-Vaca D, et al. Diabetes exacerbates inflammatory responses to ischemia-reperfusion. Circulation, 1996, 93(1): 161-167.
34. Wang C, Jiang J, Zhang X, et al. Inhibiting HMGB1 reduces cerebral ischemia reperfusion injury in diabetic mice. Inflammation, 2016, 39(6): 1862-1870.
35. Zhao L, Huang S, Liao Q, et al. RNA-seq analysis of ischemia stroke and normal brain in a tree shrew model with or without type 2 diabetes mellitus. Metab Brain Dis, 2021, 36(7): 1889-1901.
36. Zhao L, Tan S, Liao Q, et al. The neuroprotective effect and RNA-sequence analysis of postconditioning on the ischemic stroke with diabetes mellitus tree shrew model. Brain Behav, 2021, 11(11): e2354.
37. Lin HB, Li FX, Zhang JY, et al. Cerebral-cardiac syndrome and diabetes: cardiac damage after ischemic stroke in diabetic state. Front Immunol, 2021, 12: 737170.
38. Rom S, Zuluaga-Ramirez V, Gajghate S, et al. Hyperglycemia-driven neuroinflammation compromises BBB leading to memory loss in both diabetes mellitus (DM) type 1 and type 2 mouse models. Mol Neurobiol, 2019, 56(3): 1883-1896.
39. Zhao Q, Zhang F, Yu Z, et al. HDAC3 inhibition prevents blood-brain barrier permeability through Nrf2 activation in type 2 diabetes male mice. J Neuroinflammation, 2019, 16(1): 103.
40. Yuen NY, Chechneva OV, Chen YJ, et al. Exacerbated brain edema in a rat streptozotocin model of hyperglycemic ischemic stroke: evidence for involvement of blood-brain barrier Na-K-Cl cotransport and Na/H exchange. J Cereb Blood Flow Metab, 2019, 39(9): 1678-1692.
41. Wang LP, Geng J, Liu C, et al. Diabetes mellitus-related neurobehavioral deficits in mice are associated with oligodendrocyte precursor cell dysfunction. Front Aging Neurosci, 2022, 14: 846739.
42. Yatomi Y, Tanaka R, Shimada Y, et al. Type 2 diabetes reduces the proliferation and survival of oligodendrocyte progenitor cells in ishchemic white matter lesions. Neuroscience, 2015, 289: 214-223.
43. Prakash R, Li W, Qu Z, et al. Vascularization pattern after ischemic stroke is different in control versus diabetic rats: relevance to stroke recovery. Stroke, 2013, 44(10): 2875-2882.
44. Jing L, He Q, Zhang JZ, et al. Temporal profile of astrocytes and changes of oligodendrocyte-based myelin following middle cerebral artery occlusion in diabetic and non-diabetic rats. Int J Biol Sci, 2013, 9(2): 190-199.
45. Dong LD, Ma YM, Xu J, et al. Effect of hyperglycemia on microglial polarization after cerebral ischemia-reperfusion injury in rats. Life Sci, 2021, 279: 119660.
46. Fadini GP, Albiero M, Bonora BM, et al. Angiogenic abnormalities in diabetes mellitus: mechanistic and clinical aspects. J Clin Endocrinol Metab, 2019, 104(11): 5431-5444.
47. Tobin MK, Bonds JA, Minshall RD, et al. Neurogenesis and inflammation after ischemic stroke: what is known and where we go from here. J Cereb Blood Flow Metab, 2014, 34(10): 1573-1584.
48. Kim B, Feldman EL. Insulin resistance in the nervous system. Trends Endocrinol Metab, 2012, 23(3): 133-141.
49. Infante-Garcia C, Ramos-Rodriguez JJ, Garcia-Alloza M. Prediabetes and type 2 diabetes implication in central proliferation and neurogenesis. Neural Regen Res, 2015, 10(1): 28-29.
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Latest ArticlesDiabetes mellitus and ischemic stroke: current pathophysiological mechanisms and pharmaceutical research status

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