血糖变异性与胰岛β细胞功能相关性及干预靶点的研究进展

刁瑛丽; 张雨健; 宋雪楠; 张建波; 丛日平; 徐露佳; 王伟; 唐宽晓

doi:10.16766/j.cnki.issn.1674-4152.003973

血糖变异性与胰岛β细胞功能相关性及干预靶点的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.003973

1.
山东大学齐鲁医院全科医学科，山东济南 250012
2.
山东大学齐鲁医院急诊科

详细信息

通讯作者:
唐宽晓，E-mail：tangkx_ql@hotmail.com

中图分类号: R587.1 R333.3
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出版历程
- 收稿日期: 2024-11-13
- 网络出版日期: 2025-06-30

Research progress on the relationship between glucose variability and pancreatic beta cell function and the intervention targets

1.
Department of General Practice, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China

摘要

摘要: 异常的血糖波动比持续高血糖对糖尿病患者的危害更大，血糖变异性(glucose variability，GV)可反映血糖波动的情况，许多临床和基础试验表明，GV与胰岛β细胞功能密切相关，二者相互影响。GV通过氧化应激和慢性炎症反应等病理生理机制诱导胰岛β细胞的功能衰竭和胰岛素抵抗。评估GV的指标诸多，包括糖化血红蛋白(glycated hemoglobin A1c，HbA1c)、糖化血清白蛋白(glycated albumin，GA)以及自我血糖监测(self-monitoring of blood glucose，SMBG)等，这些指标均存在明显局限性。动态血糖监测(continuous glucose monitoring，CGM)技术可为研究GV新指标提供可靠工具。本文就GV与胰岛β细胞功能相关性及干预靶点的国内外研究新进展进行综述，主要内容包括：GV的定义及监测指标、GV的危害、GV引发胰岛β细胞功能障碍的可能机制、GV与胰岛β细胞功能的相关性、以GV为靶点改善胰岛β细胞功能的治疗策略等，旨在为胰岛β细胞功能的保护与恢复、深入探索糖尿病及其多种并发症的有效预防策略与创新治疗方法提供参考。
- 糖尿病 /
- 动态血糖监测 /
- 血糖变异性 /
- 胰岛β细胞功能
Abstract: Glucose variability (GV) is more harmful to diabetic patients than sustained high blood glucose levels. Glycemic variability reflects fluctuations in blood glucose, and increasing number of clinical and basic research has shown that glucose variability is closely related to the function of pancreatic beta cell, with a bidirectional influence. GV leads to functional failure of islet beta cells and insulin resistance through pathophysiological mechanisms such as oxidative stress and chronic inflammatory responses. Several indicators are used to evaluate GV, including glycated hemoglobin A1c, glycated albumin, and self-monitoring, each with obvious limitations. Continuous glucose monitoring can provide a reliable tool for studying glucose variability. This article reviews the latest research on the relationship between GV and pancreatic beta cell function, as well as potential intervention targets. Topics covered the definition and monitoring indicators of glucose variability, its harmful effects, the potential mechanisms underlying pancreatic beta cell dysfunction caused by abnormal glucose variability, the correlation between glucose variability and pancreatic beta cell function, and the therapeutic strategies aimed at improving pancreatic beta cell function by targeting glucose variability. This review provides valuable insights for the protection of pancreatic function and for the prevention and treatment of diabetes and its complications.
- Diabetes mellitus /
- Continuous glucose monitoring /
- Glucose variability /
- Pancreatic β cell function

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参考文献(40)

[1]	SUN H, SAEEDI P, KARURANGA S, et al. IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J]. Diabetes Res Clin Pract, 2022, 183: 109119. DOI: 10.1016/j.diabres.2021.109119.
[2]	ZHANG X M, SHEN Q Q. Application and management of continuous glucose monitoring in diabetic Kidney disease[J]. World J Diabetes, 2024, 15(4): 591-597. doi: 10.4239/wjd.v15.i4.591
[3]	KIRKMAN M S, SACKS D B. Glycated albumin: added value or redundancy in diabetes care?[J]. Clin Chem, 2022, 68(3): 379-381.
[4]	SACKS D B, ARNOLD M, BAKRIS G L, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus[J]. Diabetes Care, 2023, 46(10): e151-e199. doi: 10.2337/dci23-0036
[5]	DUNN T C, XU Y J, BERGENSTAL R M, et al. Personalized glycated hemoglobin in diabetes management: closing the gap with glucose management indicator[J]. Diabetes Technol Ther, 2023, 25(S3): S65-S74. doi: 10.1089/dia.2023.0146
[6]	MANOSROI W, PHIMPHILAI M, WAISAYANAND N, et al. Glycated hemoglobin variability and the risk of cardiovascular events in patients with prediabetes and type 2 diabetes mellitus: a post-hoc analysis of a prospective and multicenter study[J]. J Diabetes Investig, 2023, 14(12): 1391-1400. doi: 10.1111/jdi.14073
[7]	KIRKMAN M S, SACKS D B. Glycated albumin: added value or redundancy in diabetes care?[J]. Clin Chem, 2022, 68(3): 379-381. doi: 10.1093/clinchem/hvab261
[8]	AJJAN R A, BATTELINO T, COS X, et al. Continuous glucose monitoring for the routine care of type 2 diabetes mellitus[J]. Nat Rev Endocrinol, 2024, 20(7): 426-440. doi: 10.1038/s41574-024-00973-1
[9]	中华医学会糖尿病学分会. 中国血糖监测临床应用指南(2021年版)[J]. 中华糖尿病杂志, 2021, 13(10): 936-948. Diabetes Society of Chinese Medical Association. Clinical application guideline for blood glucose monitoring in China (2021 edition)[J]. Chinese Journal of Diabetes, 2021, 13(10): 936-948.
[10]	SEIDU S, KUNUTSOR S K, AJJAN R A, et al. Efficacy and safety of continuous glucose monitoring and intermittently scanned continuous glucose monitoring in patients with type 2 diabetes: a systematic review and meta-analysis of interventional evidence[J]. Diabetes Care, 2024, 47(1): 169-179. doi: 10.2337/dc23-1520
[11]	ELSAYED N A, ALEPPO G, ARODA V R, et al. 2. Classification and diagnosis of diabetes: standards of care in diabetes-2023[J]. Diabetes Care, 2023, 46(Supplement_1): S19-S40. doi: 10.2337/dc23-S002
[12]	MITA T, KATAKAMI N, OKADA Y, et al. Continuous glucose monitoring-derived time in range and CV are associated with altered tissue characteristics of the carotid artery wall in people with type 2 diabetes[J]. Diabetologia, 2023, 66(12): 2356-2367. doi: 10.1007/s00125-023-06013-3
[13]	DE MEULEMEESTER J, CHARLEER S, VISSER M M, et al. The association of chronic complications with time in tight range and time in range in people with type 1 diabetes: a retrospective cross-sectional real-world study[J]. Diabetologia, 2024, 67(8): 1527-1535. doi: 10.1007/s00125-024-06171-y
[14]	WAKASUGI S, MITA T, KATAKAMI N, et al. Associations between continuous glucose monitoring-derived metrics and diabetic retinopathy and albuminuria in patients with type 2 diabetes[J]. BMJ Open Diabetes Res Care, 2021, 9(1): e001923. DOI: 10.1136/bmjdrc-2020-001923.
[15]	CHANG K C, PAI Y W, LIN C H, et al. Glycemic variability' s impact on painful diabetic peripheral neuropathy in type 2 diabetes patients[J]. Sci Rep, 2024, 14(1): 22276. DOI: 10.1038/s41598-024-73472-y.
[16]	吴道爱, 金国玺, 时照明, 等. 葡萄糖在目标范围内时间和糖尿病足的相关性研究[J]. 中华全科医学, 2024, 22(3): 414-417. doi: 10.16766/j.cnki.issn.1674-4152.003415 WU D A, JIN G X, SHI Z M, et al. Correlation between time in range and diabetic foot in patients with type 2 diabetes mellitus[J]. Chinese Journal of General Practice, 2024, 22(3): 414-417. doi: 10.16766/j.cnki.issn.1674-4152.003415
[17]	ZHANG L, SUN X X, TIAN Q S, et al. Research progress on the association between glycemic variability index derived from CGM and cardiovascular disease complications[J]. Acta Diabetol, 2024, 61(6): 679-692. doi: 10.1007/s00592-024-02241-0
[18]	KLIMONTOV V V, SAIK O V, KORBUT A I, et al. Glucose variability: how does it work?[J]. Int J Mol Sci, 2021, 22(15): 7783. DOI: 10.3390/ijms22157783.
[19]	MA C F, LIU Y W, HE S L, et al. Association between glucose fluctuation during 2-hour oral glucose tolerance test, inflammation and oxidative stress markers, and β-cell function in a Chinese population with normal glucose tolerance[J]. Ann Transl Med, 2021, 9(4): 327. DOI: 10.21037/atm-20-6119.
[20]	CHEN X T, SHI C Z, WANG Y, et al. The mechanisms of glycolipid metabolism disorder on vascular injury in type 2 diabetes[J]. Front Physiol, 2022, 13: 952445. DOI: 10.3389/fphys.2022.952445.
[21]	IQBAL A, PRINCE L R, NOVODVORSKY P, et al. Effect of hypoglycemia on inflammatory responses and the response to low-dose endotoxemia in humans[J]. J Clin Endocrinol Metab, 2019, 104(4): 1187-1199. doi: 10.1210/jc.2018-01168
[22]	YE J W, DENG J J, LIANG W Q, et al. Time in range assessed by capillary blood glucose in relation to insulin sensitivity and beta-cell function in patients with type 2 diabetes mellitus: a cross-sectional study in China[J]. J Diabetes Investig, 2022, 13(11): 1825-1833. doi: 10.1111/jdi.13876
[23]	XU S Y, LI K, ZHANG Z, et al. Association between time in range, a novel measurement of glycemic control and islet secretory function in chinese patients with type 2 diabetes mellitus: an observational study[J]. Diabetes Res Clin Pract, 2021, 173: 108684. DOI: 10.1016/j.diabres.2021.108684.
[24]	ZHANG L Y, GUO K Y, TIAN Q, et al. The continuous spectrum of glycaemic variability changes with pancreatic islet function: a multicentre cross-sectional study in China[J]. Diabetes Metab Res Rev, 2022, 38(8): e3579. DOI: 10.1002/dmrr.3579.
[25]	FUHRI SNETHLAGE C M, MCDONALD T J, ORAM R D, et al. Residual β-cell function is associated with longer time in range in individuals with type 1 diabetes[J]. Diabetes Care, 2024, 47(7): 1114-1121. doi: 10.2337/dc23-0776
[26]	LIU W, MA Y K, CAI X L, et al. Preserved C-peptide secretion is associated with higher time in range (TIR) on intermittently scanned continuous glucose monitoring in Chinese adults with type 1 diabetes[J]. Endocr Connect, 2022, 11(11): e220244. DOI: 10.1530/EC-22-0244.
[27]	TANAKA K, OKADA Y, UEMURA F, et al. Associations between time in range and insulin secretory capacity in Japanese patients with type 2 diabetes[J]. Sci Rep, 2024, 14(1): 12910. DOI: 10.1038/s41598-024-63678-5.
[28]	WRONKA M, KRZEMIÑSKA J, MŁYNARSKA E, et al. The influence of lifestyle and treatment on oxidative stress and inflammation in diabetes[J]. Int J Mol Sci, 2022, 23(24): 15743. DOI: 10.3390/ijms232415743.
[29]	XU X Z, XU W, ZHUO Q Q, et al. The efficacy and safety of dapagliflozin combined with oral hypoglycemic agents in patients with type 2 diabetes: a systematic review and meta-analysis[J]. Ann Palliat Med, 2022, 11(3): 1028-1037. doi: 10.21037/apm-22-121
[30]	沈小静, 李昉, 华会, 等. 二甲双胍联合西格列汀治疗2型糖尿病患者的效果及对胰岛功能的作用[J]. 西部医学, 2024, 36(10): 1475-1479. SHEN X J, LI F, HUA H, et al. The effect of Metformin combined with Sitagliptin in treatment of type 2 diabetes patients and its effect on islet function[J]. Medical Journal of West China, 2024, 36(10): 1475-1479.
[31]	NOMOTO H, FURUSAWA S, YOKOYAMA H, et al. Improvement of beta-cell function after switching from DPP-4 inhibitors to oral semaglutide: switch-sema2 post hoc analysis[J]. J Clin Endocrinol Metab, 2024: dgae213. DOI: 10.1210/clinem/dgae213.
[32]	GRACE T, SALYER J. Use of real-time continuous glucose monitoring improves glycemic control and other clinical outcomes in type 2 diabetes patients treated with less intensive therapy[J]. Diabetes Technol Ther, 2022, 24(1): 26-31. doi: 10.1089/dia.2021.0212
[33]	RETNAKARAN R, PU J, EMERY A, et al. Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes[J]. Nat Commun, 2023, 14(1): 4514. DOI: 10.1038/s41467-023-40287-w.
[34]	CHEN P, SUN Q, XU L Y, et al. Patients with type 2 diabetes who achieve reduced postprandial glucose levels during insulin intensive therapy may have a better recovery of β-cell function[J]. Diabetes Res Clin Pract, 2024, 215: 111805. DOI: 10.1016/j.diabres.2024.111805.
[35]	GUO K Y, LI J Q, ZHANG L Y, et al. Comparing the effectiveness of continuous subcutaneous insulin infusion with multiple daily insulin injection for patients with type 1 diabetes mellitus evaluated by retrospective continuous glucose monitoring: a real-world data analysis[J]. Front Public Health, 2022, 10: 990281. DOI: 10.3389/fpubh.2022.990281.
[36]	YANG B, HAN L, WANG Y, et al. Effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections on glycaemic control among older adults with type 2 diabetes: protocol for systematic review and meta-analysis[J]. BMJ Open, 2023, 13(1): e063161. DOI: 10.1136/bmjopen-2022-063161.
[37]	YU Y, GROTH S W. Use of continuous glucose monitoring in patients following bariatric surgery: a scoping review[J]. Obes Surg, 2023, 33(8): 2573-2582. doi: 10.1007/s11695-023-06704-1
[38]	BOUGHTON C K, HOVORKA R. New closed-loop insulin systems[J]. Diabetologia, 2021, 64(5): 1007-1015. doi: 10.1007/s00125-021-05391-w
[39]	NAKAMURA T, FUJIKURA J, ANAZAWA T, et al. Reduced glycemic variability and flexible graft function after islet transplantation: a case report[J]. J Diabetes Investig, 2020, 11(6): 1677-1680. doi: 10.1111/jdi.13292
[40]	PARK Y M, YANG C M, CHO H Y. Therapeutic effects of insulin-producing human umbilical cord-derived mesenchymal stem cells in a type 1 diabetes mouse model[J]. Int J Mol Sci, 2022, 23(13): 6877. DOI: 10.3390/ijms23136877.