2型糖尿病患者脑功能连接强度的改变及其神经病理机制

陆亚姗; 赵莲萍; 黄刚; 田静; 张文文; 梁丰丽; 高艳艳; 柳瑞芳; 方燕燕

doi:10.11855/j.issn.0577-7402.1265.2023.0403

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2型糖尿病患者脑功能连接强度的改变及其神经病理机制

临床研究 | 更新时间：2023-12-13

- 2型糖尿病患者脑功能连接强度的改变及其神经病理机制
- Alteration of brain functional connectivity strength in patients with type 2 diabetes and its neuropathological mechanism
- 解放军医学杂志 2023年48卷第11期页码：1321-1327
- 作者机构：
  
  1.甘肃省人民医院放射科，甘肃兰州　730000
- 作者简介：
  
  陆亚姗，硕士研究生，主要从事2型糖尿病脑功能成像方面的研究
  赵莲萍，E-mail：lianping_zhao007@163.com
- 基金信息：
  
  国家自然科学基金(81901724;81860306);甘肃省自然科学基金(20JR5RA156;21JR7RA593);甘肃省人民医院院内科研项目(19SYPYA-2)
- DOI：10.11855/j.issn.0577-7402.1265.2023.0403
  中图分类号：
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陆亚姗, 赵莲萍, 黄刚, 等. 2型糖尿病患者脑功能连接强度的改变及其神经病理机制[J]. 解放军医学杂志, 2023, 48(11): 1321-1327.

Lu Ya-Shan,Zhao Lian-Ping,Huang Gang,et al.Alteration of brain functional connectivity strength in patients with type 2 diabetes and its neuropathological mechanism[J].Medical Journal of Chinese People′s Liberation Army,2023,48(11):1321-1327.
陆亚姗, 赵莲萍, 黄刚, 等. 2型糖尿病患者脑功能连接强度的改变及其神经病理机制[J]. 解放军医学杂志, 2023, 48(11): 1321-1327. DOI： 10.11855/j.issn.0577-7402.1265.2023.0403.

Lu Ya-Shan,Zhao Lian-Ping,Huang Gang,et al.Alteration of brain functional connectivity strength in patients with type 2 diabetes and its neuropathological mechanism[J].Medical Journal of Chinese People′s Liberation Army,2023,48(11):1321-1327. DOI： 10.11855/j.issn.0577-7402.1265.2023.0403.

摘要

目的,2,探讨2型糖尿病(T2DM)患者脑功能连接强度的改变及其神经病理机制。,方法,2,选取2017年10月－2021年3月在甘肃省人民医院就诊的56例T2DM患者为T2DM组，另选择48例健康对照者为对照组，采用静息态脑功能连接强度(FCS)和基于种子点的功能连接(FC)分析方法对T2DM患者脑功能改变进行前瞻性研究。两组均进行脑部功能磁共振扫描、临床变量采集及神经心理学测试；计算FCS值，评估静息状态下两组脑功能的变化，以组间差异显著的脑区为种子点与全脑行功能连接分析，并提取差异脑区的FCS及FC值，与空腹血糖(FPG)、糖化血红蛋白(HbA,1c,)、促甲状腺激素(TSH)水平等临床变量以及简易精神状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、画钟测验(CDT)、汉密尔顿抑郁量表(HAMD-24)、汉密尔顿焦虑量表(HAMA)评分行相关性分析。,结果,2,与对照组比较，T2DM组HAMD-24、HAMA评分明显升高(,P,<,0.01)，MoCA评分降低(,P,<,0.05)；T2DM组右侧颞中回FCS值升高(GRF矫正，体素水平,P,<,0.001，集簇水平,P,<,0.05)，且右侧颞中回-左侧前扣带皮质间FC值降低(GRF矫正，体素水平,P,<,0.001，集簇水平,P,<,0.05)。相关性分析显示，T2DM患者右侧颞中回-左侧前扣带皮质间FC值与HAMD-24评分(,r,=-0.395，,P,=0.003)、HbA,1c,水平(,r,=-0.303，,P,=0.023)呈负相关，与TSH水平呈正相关(,r,=0.324，,P,=0.017)。,结论,2,T2DM患者右侧颞中回FCS值升高，右侧颞中回-左侧前扣带皮质间FC值降低，可能是T2DM患者脑功能损害的重要神经影像学特征。HbA,1c,可能在T2DM患者脑损害过程中起重要作用。

Abstract

Objective,2,To explore the change of brain functional connectivity strength in patients with type 2 diabetes mellitus (T2DM) and its neuropathological mechanism.,Methods,2,Fifty-six T2DM patients who visited Gansu Provincial Hospital from October 2017 to March 2021 were selected as T2DM group, and 48 healthy controls were selected as control group. A prospective study was conducted on the changes in brain function in T2DM patients by analysis of resting state functional connectivity strength (FCS) and functional connectivity (FC) based on seed points. Brain functional magnetic resonance imaging, clinical variable collection, and neuropsychological testing of patients in two groups were performed. We calculate the FCS value, evaluate the brain function changes of the two groups in the resting state, take the brain regions with significant differences between the groups as the seed points and perform functional connectivity analysis with the whole brain. Correlation analysis was conducted between the FCS, FC values of the different brain regions and clinical variables such as fasting blood glucose (FPG), glycosylated hemoglobin (HbA,1c,), thyroid hormone (TSH) levels, as well as the scores of mini mental state examination (MMSE), Montreal cognitive assessment (MoCA), clock drawing test (CDT), Hamilton Depression Rating Scale (HAMD-24) and Hamilton Anxiety Scale (HAMA).,Results,2,Compared with control group, the HAMD-24 and HAMA scores in T2DM group significantly increased,(,P,<,0.01), while the MoCA scores decreased (,P,<,0.05); In T2DM group, the FCS value of the right middle temporal gyrus increased (GRF correction, voxel level ,P,<,0.001, clustering level ,P,<,0.05), and the FC value of the right middle temporal gyrus-left anterior cingulate cortex decreased (GRF correction, voxel level ,P,<,0.001, clustering level ,P,<,0.05). Correlation analysis showed that the FC value of right middle temporal gyrus-left anterior cingulate cortex in T2DM patients was negatively correlated with HAMD-24 score,(,r,=-0.395,P,=0.003), HbA,1c, level (,r,=-0.303,P,=0.023), and positively correlated with TSH level (,r,=0.324,P,=0.017).,Conclusions,2,The increase of FCS value in the right middle temporal gyrus and the decrease of FC value in the right middle temporal gyrus-left anterior cingulate cortex may be important neuroimaging features of brain function damage in T2DM patients. HbA,1c, may play an important role in the process of brain damage in T2DM patients.

关键词

糖尿病，2型磁共振成像功能连接强度认知障碍抑郁

Keywords

diabetes mellitus type 2magnetic resonance imagingfunctional connectivity strengthcognition disordersdepression

references

Yuan Z, Xiao YZ, Miao Y, et al. The relationship between glucose excursion and cognitive function in aged type 2 diabetes patients[J]. Biomed Environ Sci, 2012, 25(1): 1-7.

Singh R, Barden A, Mori T, et al. Advanced glycation end-products: a review[J]. Diabetologia, 2001, 44(2): 129-146.

Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease[J]. Nat Rev Immunol, 2011, 11(2): 98-107.

Biessels GJ, de Leeuw FE, Lindeboom J, et al. Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus[J]. J Neurol Neurosurg Psychiatry, 2006, 77(3): 304-307.

Chung CC, Pimentel D, Jor'dan AJ, et al. Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes[J]. Neurology, 2015, 85(5): 450-458.

Wang Y, Chou J, Xu ZJ, et al. Effect of dagliflozin on cognitive function in patients with type 2 diabetes mellitus combined with lacunar cerebral infarction[J]. Clin J Med Offic, 2022, 50(8): 852-854.

王雁, 仇靖, 徐智佳, 等. 达格列净对2型糖尿病合并腔隙性脑梗死患者认知功能影响[J]. 临床军医杂志, 2022, 50(8): 852-854.

Hussain S, Habib A, Singh A, et al. Prevalence of depression among type 2 diabetes mellitus patients in india: A meta-analysis[J]. Psychiatry Res, 2018, 270: 264-273.

Herder C, Schmitt A, Budden F, et al. Longitudinal associations between biomarkers of inflammation and changes in depressive symptoms in patients with type 1 and type 2 diabetes[J]. Psychoneuroendocrinology, 2018, 91: 216-225.

Lu YS, Huang G, Zhao LP. Research progress on neuropatho-physiological mechanism of patients with type 2 diabetes comorbid depression[J]. Chin J Psychiatry, 2020, 53(3): 263-266.

陆亚姗, 黄刚, 赵莲萍. 2型糖尿病共病抑郁的神经病理生理机制研究进展[J]. 中华精神科杂志, 2020, 53(3): 263-266.

Farooqi A, Khunti K, Abner S, et al. Comorbid depression and risk of cardiac events and cardiac mortality in people with diabetes: A systematic review and meta-analysis[J]. Diabetes Res Clin Pract, 2019, 156: 107816.

Wu LX, Wu W. Research progress in resting state functional magnetic resonance imaging of brain in focal dystonia[J]. Med J Chin PLA, 2022, 47(10): 1042-1048.

吴兰香, 吴伟. 静息态功能磁共振成像在局灶性肌张力障碍中的应用研究进展[J]. 解放军医学杂志, 2022, 47(10): 1042-1048.

Zang Y, He Y, Zhu C, et al. Altered baseline brain activity in children with adhd revealed by resting-state functional MRI[J]. Brain Dev, 2007, 29(2): 83-91.

Zang Y, Jiang T, Lu Y, et al. Regional homogeneity approach to fMRI data analysis[J]. Neuroimage, 2004, 22(1): 394-400.

Rosazza C, Minati L. Resting-state brain networks: literature review and clinical applications[J]. Neurol Sci, 2011, 32(5): 773-785.

Nelson PT, Smith CD, Abner EA, et al. Human cerebral neuropathology of type 2 diabetes mellitus[J]. Biochim Biophys Acta, 2009, 1792(5): 454-469.

Zhuo C, Zhu J, Qin W, et al. Functional connectivity density alterations in schizophrenia[J]. Front Behav Neurosci, 2014, 8: 404.

Liang X, Zou Q, He Y, et al. Coupling of functional connectivity and regional cerebral blood flow reveals a physiological basis for network hubs of the human brain[J]. Proc Natl Acad Sci U S A, 2013, 110(5): 1929-1934.

Zhu J, Zhuo C, Xu L, et al. Altered coupling between resting-state cerebral blood flow and functional connectivity in schizophrenia[J]. Schizophr Bull, 2017, 43(6): 1363-1374.

Liu D, Chen L, Duan S, et al. Disrupted balance of long- and short-range functional connectivity density in type 2 diabetes mellitus: A resting-state fMRI study[J]. Front Neurosci, 2018, 12: 875.

Liu L, Li W, Zhang Y, et al. Weaker functional connectivity strength in patients with type 2 diabetes mellitus[J]. Front Neurosci, 2017, 11: 390.

Cui Y, Li SF, Gu H, et al. Disrupted brain connectivity patterns in patients with type 2 diabetes[J]. AJNR Am J Neuroradiol, 2016, 37(11): 2115-2122.

Liu D, Duan S, Zhou C, et al. Altered brain functional hubs and connectivity in type 2 diabetes mellitus patients: A resting-state fMRI study[J]. Front Aging Neurosci, 2018, 10: 55.

Li Y, Liang Y, Tan X, et al. Altered functional hubs and connectivity in type 2 diabetes mellitus without mild cognitive impairment[J]. Front Neurol, 2020, 11: 1016.

Jia W, Weng J, Zhu D, et al. Standards of medical care for type 2 diabetes in China 2019[J]. Diabetes Metab Res Rev, 2019, 35(6): e3158.

Birn RM, Molloy EK, Patriat R, et al. The effect of scan length on the reliability of resting-state fMRI connectivity estimates[J]. Neuroimage, 2013, 83: 550-558.

Buckner RL, Sepulcre J, Talukdar T, et al. Cortical hubs revealed by intrinsic functional connectivity: Mapping, assessment of stability, and relation to Alzheimer's disease[J]. J Neurosci, 2009, 29(6): 1860-1873.

Zuo XN, Ehmke R, Mennes M, et al. Network centrality in the human functional connectome[J]. Cereb Cortex, 2012, 22(8): 1862-1875.

Kitzbichler MG, Henson RN, Smith ML, et al. Cognitive effort drives workspace configuration of human brain functional networks[J]. J Neurosci, 2011, 31(22): 8259-8270.

Bullmore E, Sporns O. The economy of brain network organization[J]. Nat Rev Neurosci, 2012, 13(5): 336-349.

Baker LD, Cross DJ, Minoshima S, et al. Insulin resistance and alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes[J]. Arch Neurol, 2011, 68(1): 51-57.

Qin C, Liang Y, Tan X, et al. Altered whole-brain functional topological organization and cognitive function in type 2 diabetes mellitus patients[J]. Front Neurol, 2019, 10: 599.

Whitney C, Jefferies E, Kircher T. Heterogeneity of the left temporal lobe in semantic representation and control: Priming multiple versus single meanings ofn ambiguous words[J]. Cereb Cortex, 2011, 21(4): 831-844.

Rizzolatti G. Localization of grasp representations in humans by PET: 1. Observation versus execution[J]. Exp Brain Res, 1996, 111(2): 246-252.

Goel V, Gold B, Kapur S, et al. Neuroanatomical correlates of human reasoning[J]. J Cogn Neurosci, 1998, 10(3): 293-302.

Sato W, Toichi M, Uono S, et al. Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders[J]. BMC Neurosci, 2012, 13: 99.

Wu G, Lin L, Zhang Q, et al. Brain gray matter changes in type 2 diabetes mellitus: A meta-analysis of whole-brain voxel-based morphometry study[J]. J Diabetes Complications, 2017, 31(12): 1698-1703.

Yao L, Yang C, Zhang W, et al. A multimodal meta-analysis of regional structural and functional brain alterations in type 2 diabetes[J]. Front Neuroendocrinol, 2021, 62: 100915.

Tong J, Shan C, Hu C. The value of brain resting-state functional magnetic resonance imaging on image registration algorithm in analyzing abnormal changes of neuronal activity in patients with type 2 diabetes[J]. Contrast Media Mol Imaging, 2021, 2021: 6951755.

Xia W, Wang S, Sun Z, et al. Altered baseline brain activity in type 2 diabetes: a resting-state fMRI study[J]. Psychoneuroendocrinology, 2013, 38(11): 2493-2501.

Wang WQ, Liu XF, Cao WF, et al. Altered fractional amplitude of low-frequency fluctuation off MRI signals and its correlation with cognitive impairment in type 2 diabetes mellitus patients[J]. Chin J Med Phys, 2018, 35(5): 543-548.

王伟茜, 刘新凤, 曹卫芳, 等. 2型糖尿病磁共振成像静息态低频振幅变化及其与认知受损的相关性[J]. 中国医学物理学杂志, 2018, 35(5): 543-548.

Peng J, Qu H, Peng J, et al. Abnormal spontaneous brain activity in type 2 diabetes with and without microangiopathy revealed by regional homogeneity[J]. Eur J Radiol, 2016, 85(3): 607-615.

Wong SM, Jansen JFA, Zhang CE, et al. Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease[J]. Neurology, 2019, 92(15): e1669-e1677.

Hayden MR. Type 2 diabetes mellitus increases the risk of late-onset Alzheimer's disease: Ultrastructural remodeling of the neurovascular unit and diabetic gliopathy[J]. Brain Sci, 2019, 9(10):262.

Kim YK, Han KM. Neural substrates for late-life depression: A selective review of structural neuroimaging studies[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2021, 104: 110010.

Wang S, Zhao Y, Wang X, et al. Emotional intelligence mediates the association between middle temporal gyrus gray matter volume and social anxiety in late adolescence[J]. Eur Child Adolesc Psychiatry, 2021, 30(12): 1857-1869.

Operskalski JT, Paul EJ, Colom R, et al. Lesion mapping the four-factor structure of emotional intelligence[J]. Front Hum Neurosci, 2015, 9: 649.

Anticevic A, Cole MW, Murray JD, et al. The role of default network deactivation in cognition and disease[J]. Trends Cogn Sci, 2012, 16(12): 584-592.

Yang SQ, Xu ZP, Xiong Y, et al. Altered intranetwork and internetwork functional connectivity in type 2 diabetes mellitus with and without cognitive impairment[J]. Sci Rep, 2016, 6: 32980.

Zhang D, Gao J, Yan X, et al. Altered functional connectivity of brain regions based on a meta-analysis in patients with T2DM: A resting-state fMRI study[J]. Brain Behav, 2020, 10(8): e01725.

Xia W, Luo Y, Chen Y C, et al. Disrupted functional connectivity of the amygdala is associated with depressive mood in type 2 diabetes patients[J]. J Affect Dis, 2018, 228: 207-215.

Rashedinia M, Alimohammadi M, Shalfroushan N, et al. Neuroprotective effect of syringic acid by modulation of oxidative stress and mitochondrial mass in diabetic rats[J]. Biomed Res Int, 2020, 2020: 8297984.

Ortiga-Carvalho TM, Oliveira KJ, Soares BA, et al. The role of leptin in the regulation of tsh secretion in the fed state: in vivo and in vitro studies[J]. J Endocrinol, 2002, 174(1): 121-125.

Al-Hamodi Z, Al-Habori M, Al-Meeri A, et al. Association of adipokines, leptin/adiponectin ratio and C-reactive protein with obesity and type 2 diabetes mellitus[J]. Diabetol Metab Syndr, 2014, 6(1): 99.

Schmaal L, Hibar DP, Samann PG, et al. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the enigma major depressive disorder working group[J]. Mol Psychiatry, 2017, 22(6): 900-909.

Liu CH, Tang LR, Gao Y, et al. Resting-state mapping of neural signatures of vulnerability to depression relapse[J]. J Affect Dis, 2019, 250: 371-379.

Cheng C, Dong D, Jiang Y, et al. State-related alterations of spontaneous neural activity in current and remitted depression revealed by resting-state fmri[J]. Front Psychol, 2019, 10: 245.

Tan ZS, Beiser AS, Fox CS, et al. Association of metabolic dysregulation with volumetric brain magnetic resonance imaging and cognitive markers of subclinical brain aging in middle-aged adults: the Framingham Offspring Study[J]. Diabetes Care, 2011, 34(8): 1766-1770.

Peng X, Wu X, Gong R, et al. Sub-regional anterior cingulate cortex functional connectivity revealed default network subsystem dysfunction in patients with major depressive disorder[J]. Psychol Med, 2021, 51(10): 1687-1695.

Wu Z, Fang X, Yu L, et al. Abnormal functional connectivity of the anterior cingulate cortex subregions mediates the association between anhedonia and sleep quality in major depressive disorder[J]. J Affect Dis, 2022, 296: 400-407.

Kantrowitz JT, Dong Z, Milak MS, et al. Ventromedial prefrontal cortex/anterior cingulate cortex glx, glutamate, and gaba levels in medication-free major depressive disorder[J]. Transl Psychiatry, 2021, 11(1): 419.

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