切换至 "中华医学电子期刊资源库"
高级检索
中华脑血管病杂志(电子版)

中华脑血管病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (02) : 120 -124. doi: 10.11817/j.issn.1673-9248.2022.02.011

综述

胰岛素抵抗与缺血性脑卒中关系的研究进展
梁俏丽1, 陈静娟1, 周锋1, 邵燕2, 王玉凯2, 章成国1,†()   
  1. 1. 528000　广东省佛山市第一人民医院神经内科
    2. 510000　广州，中山大学孙逸仙纪念医院神经内科
  • 收稿日期:2022-03-01 出版日期:2022-04-01
  • 通信作者: 章成国
  • 基金资助:
    登峰计划-依托互联网+大数据平台构建佛一卒中中心精准防治体系(2020A022)

Research progress in the association between insulin resistance and ischemic stroke

Qiaoli Liang1, Jingjuan Chen1, Feng Zhou1, Yan Shao2, Yukai Wang2, Chengguo Zhang1,†()   

  1. 1. Department of Neurology, the First People's Hospital of FoShan, FoShan 528000, China
    2. Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510000, china
  • Received:2022-03-01 Published:2022-04-01
  • Corresponding author: Chengguo Zhang
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

梁俏丽, 陈静娟, 周锋, 邵燕, 王玉凯, 章成国. 胰岛素抵抗与缺血性脑卒中关系的研究进展[J]. 中华脑血管病杂志(电子版), 2022, 16(02): 120-124.

Qiaoli Liang, Jingjuan Chen, Feng Zhou, Yan Shao, Yukai Wang, Chengguo Zhang. Research progress in the association between insulin resistance and ischemic stroke[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2022, 16(02): 120-124.

胰岛素抵抗是胰岛素介导的组织中葡萄糖代谢控制的缺陷，与血糖、脂肪、能量代谢及神经调节密切相关，可通过炎症、氧化应激、损伤内皮细胞及促进神经元凋亡导致动脉粥样硬化，减少细胞灌注等途径引起神经元的损伤、凋亡，从而导致缺血性脑卒中及认知功能障碍等事件的发生。新近药物研究发现改善胰岛素抵抗从而降低心脑血管事件发生风险已成为医学界日益关注的议题。钠-葡萄糖协同转运蛋白-2抑制剂恩格列净通过调节下丘脑对胰岛素反应，可增加大脑的胰岛素敏感性，有望成为新的治疗靶点，预防或延缓缺血性脑卒中；新上市的胰岛素增敏剂能同时调节血糖和血脂代谢，改善代谢综合征，在脑卒中预防与治疗中有广阔的应用前景。

关键词: 胰岛素抵抗, 缺血性脑卒中, 炎症, 胰岛素增敏剂

Insulin resistance is an impaired insulin-mediated condition of glucose metabolism control, which is closely related with blood sugar, fat and energy metabolism and nervous regulation. It can result in inflammation, oxidative stress, endothelium damage, and neuronal apoptosis which brings about atherosclerosis. In addition, it can cause hypoperfusion causing neuron damage and apoptosis, which eventually leads to ischemic stroke and cognitive dysfunction. Recently, pharmacological findings that improving insulin resistance can reduce the risk of cardiovascular and cerebrovascular events, have become a growing field in the medical academy. Sodium-dependent glucose transporters-2 inhibitor Empagliflozin, which increases the insulin sensitivity in the brain by regulating hypothalamus response to insulin, is expected to become a new therapeutic approach to prevent or delay ischemic stroke. The newly-listed insulin sensitizer can simultaneously regulate the metabolism of blood glucose and blood lipids , improve the metabolic syndrome, and has a promising application in the prevention and treatment of stroke.

Key words: Insulin resistance, Ischemic stroke, Inflammation, Insulin sensitizing agent
1
Christopher JL Murray GA, Stevens LA. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019 [J]. Lancet, 2020, 396(10258): 1204-1222.
2
王亚楠, 吴思缈, 刘鸣. 中国脑卒中15年变化趋势和特点 [J]. 华西医学, 2021, 36(6): 803-807.
3
陈亚荣, 尹春, 黄佩瑶, 等. 糖尿病与脑卒中发病风险的前瞻性研究 [J]. 中华疾病控制杂志, 2022, 26(1): 74-79.
4
Gray CS, Scott JF, French JM, et al. Prevalence and prediction of unrecognised diabetes mellitus and impaired glucose tolerance following acute stroke [J]. Age Ageing, 2004, 33(1): 71-77.
5
Bhaskar S. Impact of obesity-induced type 2 diabetes on long-term outcomes following stroke [J]. Clin Sci (Lond), 2019, 133(14): 1603-1607.
6
Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease [J]. Diabetes, 1988, 37(12): 1595-1607.
7
James DE, Stöckli J, Birnbaum MJ. The aetiology and molecular landscape of insulin resistance [J]. Nat Rev Mol Cell Biol, 2021, 22(11): 751-771.
8
Sánchez-Iñigo L, Navarro-González D, Fernández-Montero A, et al. Risk of incident ischemic stroke according to the metabolic health and obesity states in the Vascular-Metabolic CUN cohort [J]. Int J Stroke, 2017, 12(2): 187-191.
9
Cho IY, Chang Y, Sung E, et al. Weight change and the development of nonalcoholic fatty liver disease in metabolically healthy overweight individuals [J]. Clin Gastroenterol Hepatol, 2022, 20(3): e583-e599.
10
Meigs JB. Epidemiology of the insulin resistance syndrome [J]. Curr Diab Rep, 2003, 3(1): 73-79.
11
Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity [J]. Circulation, 2009, 120(16): 1640-1645.
12
Tagi VM, Chiarelli F. Obesity and insulin resistance in children [J]. Curr Opin Pediatr, 2020, 32(4): 582-588.
13
Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance [J]. Physiol Rev, 2018, 98(4): 2133-2223.
14
Paccoud R, Saint-Laurent C, Piccolo E, et al. SHP2 drives inflammation-triggered insulin resistance by reshaping tissue macrophage populations [J]. Sci Transl Med, 2021, 13(591):eabe2587.
15
Pomytkin I, Costa-Nunes JP, Kasatkin V, et al. Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment [J]. CNS Neurosci Ther, 2018, 24(9): 763-774.
16
Peineau S, Taghibiglou C, Bradley C, et al. LTP inhibits LTD in the hippocampus via regulation of GSK3beta [J]. Neuron, 2007, 53(5): 703-717.
17
韩芸峰, 来璇, 杨军, 等. 代谢综合征与血管性认知障碍关系的研究进展 [J/OL]. 中华脑血管病杂志(电子版), 2020, 14(4): 234-237.
18
Owei I, Jain N, Jones D, et al. Physiology of glycemic recovery and stabilization after hyperinsulinemic euglycemic clamp in healthy subjects [J]. J Clin Endocrinol Metab, 2018, 103(11): 4155-4162.
19
Muniyappa R, Lee S, Chen H, et al. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage [J]. Am J Physiol Endocrinol Metab, 2008, 294(1): E15-E26.
20
Fitzgibbons TP, Czech MP. Emerging evidence for beneficial macrophage functions in atherosclerosis and obesity-induced insulin resistance [J]. J Mol Med (Berl), 2016, 94(3): 267-275.
21
Gaillard T, Miller E. Guidelines for stroke survivors with diabetes mellitus [J]. Stroke, 2018, 49(6): e215-e217.
22
Thacker EL, Psaty BM, McKnight B, et al. Fasting and post-glucose load measures of insulin resistance and risk of ischemic stroke in older adults [J]. Stroke, 2011, 42(12): 3347-3351.
23
Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies [J]. Lancet, 2010, 375(9733): 2215-2222.
24
Zabala A, Darsalia V, Lind M, et al. Estimated glucose disposal rate and risk of stroke and mortality in type 2 diabetes: a nationwide cohort study [J]. Cardiovasc Diabetol, 2021, 20(1): 202.
25
Kwok MK, Kawachi I, Rehkopf D, et al. The role of cortisol in ischemic heart disease, ischemic stroke, type 2 diabetes, and cardiovascular disease risk factors: a bi-directional Mendelian randomization study [J]. BMC Med, 2020, 18(1): 363.
26
Dearborn JL, Viscoli CM, Inzucchi SE, et al. Metabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease [J]. Int J Stroke, 2019, 14(6): 639-645.
27
Åberg D, Åberg ND, Jood K, et al. Homeostasis model assessment of insulin resistance and outcome of ischemic stroke in non-diabetic patients - a prospective observational study [J]. BMC Neurol, 2019, 19(1): 177.
28
Mi D, Wang Y, Wang Y, et al. Insulin resistance is an independent risk factor for early neurological deterioration in non-diabetic patients with acute ischemic stroke [J]. Neurol Sci, 2020, 41(6): 1467-1473.
29
Wieberdink RG, Koudstaal PJ, Hofman A, et al. Insulin resistance and the risk of stroke and stroke subtypes in the nondiabetic elderly [J]. Am J Epidemiol, 2012, 176(8): 699-707.
30
Gerstein HC, Ferrannini E, Riddle MC, et al. Insulin resistance and cardiovascular outcomes in the ORIGIN trial [J]. Diabetes Obes Metab, 2018, 20(3): 564-570.
31
Gu T, Yang Q, Ying G, et al. Lack of association between insulin resistance as estimated by homeostasis model assessment and stroke risk: a systematic review and meta-analysis [J]. Med Hypotheses, 2020, 141: 109700.
32
Chang Y, Kim CK, Kim MK, et al. Insulin resistance is associated with poor functional outcome after acute ischemic stroke in non-diabetic patients [J]. Sci Rep, 2021, 11(1): 1229.
33
Ago T, Matsuo R, Hata J, et al. Insulin resistance and clinical outcomes after acute ischemic stroke [J]. Neurology, 2018, 90(17): e1470-e1477.
34
Jing J, Pan Y, Zhao X, et al. Insulin resistance and prognosis of nondiabetic patients with ischemic stroke: The ACROSS-China Study (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) [J]. Stroke, 2017, 48(4): 887-893.
35
Baron AD, Steinberg HO, Chaker H, et al. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans [J]. J Clin Invest, 1995, 96(2): 786-792.
36
Sakai S, Tanimoto K, Imbe A, et al. Decreased β-cell function is associated with reduced skeletal muscle mass in Japanese subjects without diabetes [J]. PLoS One, 2016, 11(9): e0162603.
37
Yaghi S, Furie KL, Viscoli CM, et al. Pioglitazone prevents stroke in patients with a recent transient ischemic attack or ischemic stroke: a planned secondary analysis of the IRIS trial (insulin resistance intervention after stroke) [J]. Circulation, 2018, 137(5): 455-463.
38
Kim BJ, Lee SH, Jung KH, et al. Dynamics of obesity paradox after stroke, related to time from onset, age, and causes of death [J]. Neurology, 2012, 79(9): 856-863.
39
Niewada M, Michel P. Lifestyle modification for stroke prevention: facts and fiction [J]. Curr Opin Neurol, 2016, 29(1): 9-13.
40
Mirabelli M, Chiefari E, Arcidiacono B, et al. Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases [J]. Nutrients, 2020, 12(4)
41
Tettamanzi F, Bagnardi V, Louca P, et al. A high protein diet is more effective in improving insulin resistance and glycemic variability compared to a mediterranean diet-a cross-over controlled inpatient dietary study [J]. Nutrients, 2021, 13(12):4380.
42
张晓晓, 郑跃, 马玲,等. 有氧运动训练对脑卒中患者胰岛素抵抗及认知水平的影响 [J]. 中国医刊, 2020, 55(4): 434-437.
43
Inzucchi SE, Viscoli CM, Young LH, et al. Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease [J]. Diabetes Care, 2016, 39(10): 1684-1692.
44
Hung YC, Chiu LT, Huang HY, et al. Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study [J]. Cardiovasc Diabetol, 2020, 19(1): 94.
45
Spence JD, Viscoli CM, Inzucchi SE, et al. Pioglitazone therapy in patients with stroke and prediabetes: a post hoc analysis of the IRIS randomized clinical trial [J]. JAMA Neurol, 2019, 76(5): 526-535.
46
Kaku K, Wanner C, Anker SD, et al. The effect of empagliflozin on the total burden of cardiovascular and hospitalization events in the Asian and non-Asian populations of the EMPA-REG OUTCOME trial of patients with type 2 diabetes and cardiovascular disease [J]. Diabetes Obes Metab, 2022, 24(4): 662-674.
47
Ji L, Dong X, Li Y, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30-week, double-blind, phase 3a, randomized trial [J]. Diabetes Obes Metab, 2021, 23(2): 404-414.
[1] 韩圣瑾, 周正武, 翁云龙, 黄鑫. 碳酸氢钠林格液联合连续性肾脏替代疗法对创伤合并急性肾损伤患者炎症水平及肾功能的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(05): 376-381.
[2] 陈大敏, 曹晓刚, 曹能琦. 肥胖对胃癌患者手术治疗效果的影响研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 651-653.
[3] 贾成朋, 王代宏, 陈华, 孙备. 可切除性胰腺癌预后术前预测模型的建立及应用[J]. 中华普外科手术学杂志(电子版), 2023, 17(05): 566-570.
[4] 伍学成, 李远伟, 袁武雄, 王建松, 石泳中, 卢强, 李卓, 陈佳, 刘哲, 滕伊漓, 高智勇. 炎症介质谱联合降钙素原在尿源性脓毒血症中的诊断价值[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 476-480.
[5] 王可, 范彬, 李多富, 刘奎. 两种疝囊残端处理方法在经腹腹膜前腹股沟疝修补术中的疗效比较[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 692-696.
[6] 熊欢庆, 李玉娟, 陈键, 刘刚, 李志超, 金发光. 丹参酮IIA及苦参碱组方对脂多糖致小鼠急性肺损伤的协同保护作用[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 455-459.
[7] 许磊, 孙杰, 陈先志, 张家泉, 李旺勇, 冯其柱, 王琦. 血液净化治疗在高血脂性重症胰腺炎中的应用[J]. 中华肝脏外科手术学电子杂志, 2023, 12(04): 464-468.
[8] 郝然, 魏姗珊, 吴倩如, 李学民, 翟长斌. 干燥综合征血清微量元素变化及其与疾病严重程度的相关性研究[J]. 中华眼科医学杂志(电子版), 2023, 13(04): 215-220.
[9] 尚慧娟, 袁晓冬. 机械取栓术后应用依达拉奉右崁醇对急性缺血性脑卒中预后的改善[J]. 中华神经创伤外科电子杂志, 2023, 09(05): 295-301.
[10] 邹勇, 顾应江, 丁昊, 杨呈浩, 陈岷辉, 蔡昱. 基于Nrf2/HO-1及NF-κB信号通路探讨葛根素对大鼠脑出血后早期炎症反应及氧化应激反应的影响[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(05): 271-277.
[11] 屈霄, 王靓, 陆萍, 何斌, 孙敏. 外周血炎症因子及肠道菌群特征与活动性溃疡性结肠炎患者病情的相关性分析[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 466-470.
[12] 朱风尚, 舍玲, 丁永年, 杨长青. 警惕炎症性肠病与少见肠道疾病的鉴别诊断[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 273-276.
[13] 张许平, 刘佳成, 张舸, 杜艳姣, 李韶, 商丹丹, 王浩, 李艳, 段智慧. CYP2C19基因多态性联合血栓弹力图指导大动脉粥样硬化型非致残性缺血性脑血管事件患者抗血小板治疗的效果[J]. 中华脑血管病杂志(电子版), 2023, 17(05): 477-481.
[14] 刘感哲, 艾芬. MiRNA-210通过抑制HIF-1α的表达改善大鼠血管性认知功能障碍[J]. 中华脑血管病杂志(电子版), 2023, 17(05): 489-494.
[15] 李昕, 李永凯, 江树青, 夏来百提姑·赛买提, 杨建中. 急性缺血性脑卒中静脉溶栓后出血转化相关危险因素分析[J]. 中华脑血管病杂志(电子版), 2023, 17(04): 331-336.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号