上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2022 , Vol. 42 >Issue 2: 235 - 240

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.02.016

综述

糖尿病患者血糖波动异常与认知功能障碍关系的研究进展

  • 张蓉 ,
  • 陆丽 ,
  • 王亚昕 ,
  • 董文倩 ,
  • 张宇 ,
  • 周健
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  • 1.上海交通大学医学院，上海 200025
    2.上海交通大学医学院附属第六人民医院内分泌代谢科，上海市糖尿病研究所，上海市糖尿病重点实验室，上海市糖尿病临床医学中心，上海 200233
张蓉（1998—），女，本科生；电子信箱：517713910016@sjtu.edu.cn
张蓉（1998—），女，本科生；电子信箱：517713910016@sjtu.edu.cn
周健，电子信箱：zhoujian@sjtu.edu.cn。

收稿日期: 2021-08-31

  网络出版日期: 2022-01-24

基金资助

上海市教育委员会高峰高原学科建设计划(20161430);上海市“医苑新星”青年医学人才培养资助计划-杰出青年医学人才类

收起

Research progress in the relationship between abnormal blood glucose fluctuation and cognitive dysfunction of patients with diabetes mellitus

  • Rong ZHANG ,
  • Li LU ,
  • Yaxin WANG ,
  • Wenqian DONG ,
  • Yu ZHANG ,
  • Jian ZHOU
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  • 1.Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    2.Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai 200233, China
ZHOU Jian, E-mail: zhoujian@sjtu.edu.cn.

Received date: 2021-08-31

  Online published: 2022-01-24

Supported by

Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20161430);Shanghai "Rising Stars of Medical Talent" Youth Development Program-Outstanding Youth Medical Talents

Fold

摘要

糖尿病不仅可导致大血管和微血管发生病变，还会加速认知功能障碍的发生与发展，增加罹患痴呆的风险。研究表明，糖尿病所致认知功能障碍与血糖升高及血糖波动异常均相关，其发病机制可能与胰岛素抵抗、氧化应激、脑血管病变、炎症损伤、脑细胞凋亡以及β淀粉样蛋白聚集等有关。目前，关于糖尿病患者认知功能障碍的药物治疗仍处于探索阶段，有研究发现部分降糖药物（如胰高血糖素样肽-1受体激动剂）或可改善该类患者的认知功能障碍，但仍需大样本随机对照研究进一步明确。该文对认知功能障碍的评估方法，血糖波动异常对认知功能障碍的影响和相关病理生理机制，以及不同降糖药物对糖尿病患者认知功能障碍的作用进行综述。

关键词： 糖尿病; 认知功能障碍; 血糖波动异常; 降糖药物

本文引用格式

张蓉 , 陆丽 , 王亚昕 , 董文倩 , 张宇 , 周健 . 糖尿病患者血糖波动异常与认知功能障碍关系的研究进展[J]. 上海交通大学学报（医学版）, 2022 , 42(2) : 235 -240 . DOI: 10.3969/j.issn.1674-8115.2022.02.016

Abstract

Diabetes can not only cause pathological changes in both large vessels and microvessels, but also accelerate the occurrence and development of cognitive dysfunction, increasing the risk of dementia. Studies have shown that diabetes-induced cognitive dysfunction is associated with elevated blood glucose and abnormal glucose fluctuation, and its pathogenesis is closely related to insulin resistance, oxidative stress, cerebrovascular lesions, inflammatory damage, brain cell apoptosis, as well as amyloid β-protein accumulation. At present, drug therapy for diabetic patients with cognitive dysfunction is still in the exploratory stage. It has been found that some hypoglycemic drugs, such as glucagon like peptide -1 receptor agonist, can improve cognitive dysfunction in these patients. However, it still needs to be further clarified by randomized controlled trails with large sample size. This article reviews the assessment methods of cognitive dysfunction, the effects of abnormal glucose fluctuation on cognitive dysfunction, and the pathophysiological mechanisms involved, as well as the effects of different hypoglycemic agents on cognitive dysfunction in patients with diabetes.

Key words： diabetes mellitus; cognitive dysfunction; abnormal blood glucose fluctuation; hypoglycemic agent

参考文献

1 中华医学会内分泌学分会, 余学锋, 赵家军, 等. 糖尿病患者认知功能障碍专家共识[J].中华糖尿病杂志, 2021, 13(7): 678-694.
2 XU W, CARACCIOLO B, WANG H X, et al. Accelerated progression from mild cognitive impairment to dementia in people with diabetes[J]. Diabetes, 2010, 59(11): 2928-2935.
3 ZHENG F F, YAN L, YANG Z C, et al. HbA1c, diabetes and cognitive decline: The English Longitudinal Study of Ageing[J]. Diabetologia, 2018, 61(4): 839-848.
4 ZHENG B, SU B W, PRICE G, et al. Glycemic control, diabetic complications, and risk of dementia in patients with diabetes: results from a large U.K. Cohort study[J]. Diabetes Care, 2021, 44(7): 1556-1563.
5 XIA W Q, LUO Y, CHEN Y C, et al. Glucose fluctuations are linked to disrupted brain functional architecture and cognitive impairment[J]. J Alzheimers Dis, 2020, 74(2): 603-613.
6 PALTA P, CARLSON M C, CRUM R M, et al. Diabetes and cognitive decline in older adults: the Ginkgo Evaluation of Memory Study[J]. J Gerontol A Biol Sci Med Sci, 2017, 73(1): 123-130.
7 BIESSELS G J, JANSSEN J, VAN DEN BERG E, et al. Rationale and design of the CAROLINA?-cognition substudy: a randomised controlled trial on cognitive outcomes of linagliptin versus glimepiride in patients with type 2 diabetes mellitus[J]. BMC Neurol, 2018, 18(1): 7.
8 YANG X, CHEN Y Q, ZHANG W S, et al. Association between inflammatory biomarkers and cognitive dysfunction analyzed by MRI in diabetes patients[J]. Diabetes Metab Syndr Obes, 2020, 13: 4059-4065.
9 WANG H, TAN L, WANG H F, et al. Magnetic resonance spectroscopy in Alzheimer's disease: systematic review and meta-analysis[J]. J Alzheimers Dis, 2015, 46(4): 1049-1070.
10 ALOTAIBI A, TENCH C, STEVENSON R, et al. Investigating brain microstructural alterations in type 1 and type 2 diabetes using diffusion tensor imaging: a systematic review[J]. Brain Sci, 2021, 11(2): 140.
11 HU B, YAN L F, SUN Q, et al. Disturbed neurovascular coupling in type 2 diabetes mellitus patients: evidence from a comprehensive fMRI analysis[J]. Neuroimage Clin, 2019, 22: 101802.
12 DANNE T, NIMRI R, BATTELINO T, et al. International consensus on use of continuous glucose monitoring[J]. Diabetes Care, 2017, 40(12): 1631-1640.
13 BATTELINO T, DANNE T, BERGENSTAL R M, et al. Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range[J]. Diabetes Care, 2019, 42(8): 1593-1603.
14 LU J Y, MA X J, ZHANG L, et al. Glycemic variability modifies the relationship between time in range and hemoglobin A1c estimated from continuous glucose monitoring: a preliminary study[J]. Diabetes Res Clin Pract, 2020, 161: 108032.
15 LU J Y, MA X J, SHEN Y, et al. Time in range is associated with carotid intima-media thickness in type 2 diabetes[J]. Diabetes Technol Ther, 2020, 22(2): 72-78.
16 LU J Y, MA X J, ZHOU J, et al. Association of time in range, as assessed by continuous glucose monitoring, with diabetic retinopathy in type 2 diabetes[J]. Diabetes Care, 2018, 41(11): 2370-2376.
17 BECK R W, BERGENSTAL R M, RIDDLESWORTH T D, et al. Validation of time in range as an outcome measure for diabetes clinical trials[J]. Diabetes Care, 2019, 42(3): 400-405.
18 MAYEDA L, KATZ R, AHMAD I, et al. Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease[J]. BMJ Open Diabetes Res Care, 2020, 8(1): e000991.
19 GUO Q Y, ZANG P, XU S Y, et al. Time in range, as a novel metric of glycemic control, is reversely associated with presence of diabetic cardiovascular autonomic neuropathy independent of HbA1c in Chinese type 2 diabetes[J]. J Diabetes Res, 2020, 2020: 5817074.
20 RIZZO M R, MARFELLA R, BARBIERI M, et al. Relationships between daily acute glucose fluctuations and cognitive performance among aged type 2 diabetic patients[J]. Diabetes Care, 2010, 33(10): 2169-2174.
21 ZHONG Y, ZHANG X Y, 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.
22 DUNGAN K M, BUSE J B, LARGAY J, et al. 1, 5-anhydroglucitol and postprandial hyperglycemia as measured by continuous glucose monitoring system in moderately controlled patients with diabetes[J]. Diabetes Care, 2006, 29(6): 1214-1219.
23 RAWLINGS A M, SHARRETT A R, MOSLEY T H, et al. Glucose peaks and the risk of dementia and 20-year cognitive decline[J]. Diabetes Care, 2017, 40(7): 879-886.
24 QUINCOZES-SANTOS A, BOBERMIN L D, DE ASSIS A M, et al. Fluctuations in glucose levels induce glial toxicity with glutamatergic, oxidative and inflammatory implications[J]. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(1): 1-14.
25 MAIORINO M I, CASCIANO O, VOLPE E D, et al. Reducing glucose variability with continuous subcutaneous insulin infusion increases endothelial progenitor cells in type 1 diabetes: an observational study[J]. Endocrine, 2016, 52(2): 244-252.
26 WANG H, DENG J L, CHEN L, et al. Acute glucose fluctuation induces inflammation and neurons apoptosis in hippocampal tissues of diabetic rats[J]. J Cell Biochem, 2019. doi: 10.1002/jcb.29523.
27 HSIEH C F, LIU C K, LEE C T, et al. Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation[J]. Sci Rep, 2019, 9(1): 840.
28 KSHIRSAGAR V, THINGORE C, JUVEKAR A. Insulin resistance: a connecting link between Alzheimer's disease and metabolic disorder[J]. Metab Brain Dis, 2021, 36(1): 67-83.
29 NGUYEN T T, TA Q T H, NGUYEN T K O, et al. Type 3 diabetes and its role implications in Alzheimer's disease[J]. Int J Mol Sci, 2020, 21(9): 3165.
30 刘涵, 侯新国, 陈丽. 关于2型糖尿病患者认知功能障碍机制的研究进展[J]. 中华糖尿病杂志, 2021, 13(7): 737-739.
31 JO D, YOON G, SONG J. Role of exendin-4 in brain insulin resistance, mitochondrial function, and neurite outgrowth in neurons under palmitic acid-induced oxidative stress[J]. Antioxidants (Basel), 2021, 10(1): 78.
32 CUKIERMAN-YAFFE T, GERSTEIN H C, COLHOUN H M, et al. Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial[J]. Lancet Neurol, 2020, 19(7): 582-590.
33 ZHANG Z, ZHANG B, WANG X, et al. Olfactory dysfunction mediates adiposity in cognitive impairment of type 2 diabetes: insights from clinical and functional neuroimaging studies[J]. Diabetes Care, 2019, 42(7): 1274-1283.
34 BIESSELS G J, VERHAGEN C, JANSSEN J, et al. Effect of linagliptin on cognitive performance in patients with type 2 diabetes and cardiorenal comorbidities: the CARMELINA Randomized Trial[J]. Diabetes Care, 2019, 42(10): 1930-1938.
35 ATES BULUT E, SAHIN ALAK Z Y, DOKUZLAR O, et al. Cognitive and metabolic outcomes of vildagliptin addition to the therapy in patients with type 2 diabetes mellitus: 26 week follow-up study[J]. Arch Gerontol Geriatr, 2020, 88: 104013.
36 HIERRO-BUJALANCE C, INFANTE-GARCIA C, MARCO ADEL, et al. Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes[J]. Alzheimers Res Ther, 2020, 12(1): 40.
37 PERNA S, MAINARDI M, ASTRONE P, et al. 12-month effects of incretins versus SGLT2-Inhibitors on cognitive performance and metabolic profile. A randomized clinical trial in the elderly with type-2 diabetes mellitus[J]. Clin Pharmacol, 2018, 10: 141-151.
38 CUKIERMAN-YAFFE T, BOSCH J, DIAZ R, et al. Effects of basal insulin glargine and omega-3 fatty acid on cognitive decline and probable cognitive impairment in people with dysglycaemia: a substudy of the ORIGIN trial[J]. Lancet Diabetes Endocrinol, 2014, 2(7): 562-572.
39 WEINSTEIN G, DAVIS-PLOURDE K L, CONNER S, et al. Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: pooled analysis from 5 cohorts[J]. PLoS One, 2019, 14(2): e0212293.
40 SAMARAS K, MAKKAR S, CRAWFORD J D, et al. Metformin use is associated with slowed cognitive decline and reduced incident dementia in older adults with type 2 diabetes: the Sydney Memory and Ageing Study[J]. Diabetes Care, 2020, 43(11): 2691-2701.
41 DE LA MONTE S M, TONG M, WANDS J R. The 20-year voyage aboard the journal of Alzheimer's disease: docking at 'type 3 diabetes', environmental/exposure factors, pathogenic mechanisms, and potential treatments[J]. J Alzheimers Dis, 2018, 62(3): 1381-1390.
42 XUE M, XU W, OU Y N, et al. Diabetes mellitus and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 144 prospective studies[J]. Ageing Res Rev, 2019, 55: 100944.
43 BURNS D K, ALEXANDER R C, WELSH-BOHMER K A, et al. Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial[J]. Lancet Neurol, 2021, 20(7): 537-547.
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