初诊2型糖尿病患者中肝脏胰岛素清除率与临床特点及胃肠激素相关性的初步分析

doi:10.3969/j.issn.1006-7795.2021.05.020

摘要/Abstract

摘要： 目的探讨我国初诊2型糖尿病患者中肝脏胰岛素清除率(hepatic insulin clearance,HIC)与胰岛素抵抗、胰岛功能及胃肠激素的相关性。方法纳入首都医科大学附属北京世纪坛医院内分泌科初诊2型糖尿病患者112例,收集临床资料,行120 min口服葡萄糖耐量(oral glucose tolerance test, OGTT)试验,同时检测0、3、60及120 min葡萄糖、胰岛素及C肽浓度,并采用多重检测系统测定血清中肠抑胃肽(gastric inhibitory polypeptide, GIP)、胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)及饥饿素(ghrelin)的浓度。根据OGTT实验结果,计算患者HIC值。再依据HIC值的中位数将患者分为高HIC组与低HIC组,比较两组患者临床特征及胃肠激素浓度的差异。结果高HIC组患者OGTT后血糖明显高于低HIC组 (P<0.05);胰岛素抵抗方面,低HIC组患者稳态模型胰岛素抵抗指数(homeostasis model assessment-IR, HOMA-IR)较高、反映胰岛素敏感性的Matsuda指数较低(P<0.05);高HIC组患者稳态模型胰岛β细胞功能指数(homeostasis model assessment-β,HOMA-β)等评估胰岛功能的指标明显降低(P<0.05);高HIC组患者空腹ghrelin降低,葡萄糖负荷后120 min对ghrelin的抑制程度显减弱 (P<0.05);但两组患者空腹及葡萄糖负荷后的GIP与GLP-1浓度差异无统计学意义(P>0.05)。结论在汉族2型糖尿病患者中,较高的肝脏胰岛素清除率与较差的胰岛功能相关,较低的肝脏胰岛素清除率与相对严重的胰岛素抵抗相关,同时胃肠激素ghrelin可能与患者肝脏胰岛素清除率存在相关性,为我国T2DM患者防治工作提供新的理论依据。

关键词: 2型糖尿病, 肝脏胰岛素清除率, 胃肠激素

Abstract: Objective To explore the correlation between hepatic insulin clearance (HIC) and insulin resistance, β cell function and gut hormone in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods Clinical data from newly diagnosed Chinese T2DM patients was collected. A 120-min oral glucose tolerance test (OGTT) was conducted. Meanwhile, serum glucose, insulin, C peptide, gastric inhibitory polypeptide(GIP), glucagon-like peptide-1(GLP-1) and ghrelin at 0, 30, 60 and 120 min were all detected during OGTT. HIC was calculated from OGTT results. Patients were divided into high HIC group and low HIC group according to HIC levels. Clinical characters and gut hormones were compared between the two groups. Results Concentrations of glucose after OGTT in high HIC group were significantly higher than those in low HIC group (P<0.05). Homeostasis model assessment-IR (HOMA-IR) was increased and Matsuda index was decreased in low HIC group compared with high HIC group (P<0.05). Meanwhile, homeostasis model assessment-β (HOMA-β) was lower in patients with higher HIC (P<0.05). Importantly, patients in high HIC group were found with lower fasting ghrelin, and poorer ghrelin inhibition at 120 min after 75 g glucose load (P<0.05). Neither base levels nor concentrations during OGTT were different in GIP and GLP-1 analysis. Conclusion In Chinese patients with newly diagnosed T2DM, higher HIC is correlated with poorer islet function, while lower HIC is found in patients with relatively severe insulin resistance. Moreover, gut hormone ghrelin may be associated with hepatic insulin clearance. This research may provide new evidences for diabetes prevention and treatment in Chinese patients.

Key words: type 2 diabetes mellitus, hepatic insulin clearance, gut hormone

中图分类号:

R587

张冬雪, 文祯, 孙玉燕, 姜涛. 初诊2型糖尿病患者中肝脏胰岛素清除率与临床特点及胃肠激素相关性的初步分析[J]. 首都医科大学学报, 2021, 42(5): 822-828.

Zhang Dongxue, Wen Zhen, Sun Yuyan, Jiang Tao. Association between hepatic insulin clearance,clinical characteristics and gut hormone in Chinese patients with newly diagnosed type 2 diabetes mellitus[J]. Journal of Capital Medical University, 2021, 42(5): 822-828.

参考文献

[1] Fosam A, Sikder S, Abel B S, et al. Reduced insulin clearance and insulin-degrading enzyme activity contribute to hyperinsulinemia in african americans[J]. J Clin Endocrinol Metab, 2020,105(4):1835-1846.
[2] Pivovarova O, Bernigau W, Bobbert T, et al. Hepatic insulin clearance is closely related to metabolic syndrome components[J]. Diabetes Care, 2013,36(11):3779-3785.
[3] Bergman R N, Piccinini F, Kabir M, et al. Hypothesis: role of reduced hepatic insulin clearance in the pathogenesis of type 2 diabetes[J]. Diabetes, 2019,68(9):1709-1716.
[4] Hakim O, Bello O, Bonadonna R C, et al. Ethnic differences in intrahepatic lipid and its association with hepatic insulin sensitivity and insulin clearance between men of black and white ethnicity with early type 2 diabetes[J]. Diabetes Obes Metab, 2019,21(9):2163-2168.
[5] Okura T, Fujioka Y, Nakamura R, et al. Hepatic insulin clearance is increased in patients with high HbA1c type 2 diabetes: a preliminary report[J]. BMJ Open Diabetes Res Care, 2020,8(1):e001149.
[6] Gastaldelli A, Ghani M A, DeFronzo R A. Adaptation of insulin clearance to metabolic demand is a key determinant of glucose tolerance[J]. Diabetes, 2021,70(2):377-385.
[7] Gauna C, Uitterlinden P, Kramer P, et al. Intravenous glucose administration in fasting rats has differential effects on acylated and unacylated ghrelin in the portal and systemic circulation: a comparison between portal and peripheral concentrations in anesthetized rats[J]. Endocrinology, 2007,148(11):5278-5287.
[8] Meier J J, Holst J J, Schmidt W E, et al. Reduction of hepatic insulin clearance after oral glucose ingestion is not mediated by glucagon-like peptide 1 or gastric inhibitory polypeptide in humans[J]. Am J Physiol Endocrinol Metab, 2007,293(3):849-856.
[9] Matsubayashi Y, Yoshida A, Suganami H, et al. Role of fatty liver in the association between obesity and reduced hepatic insulin clearance[J]. Diabetes Metab, 2018,44(2):135-142.
[10]Keyhani-Nejad F, Barbosa Yanez R L, Kemper M, et al. Endogenously released GIP reduces and GLP-1 increases
hepatic insulin extraction[J]. Peptides, 2020,125:170231.
[11]Quiñones M, Fernø J, Al-Massadi O. Ghrelin and liver disease[J]. Rev Endocr Metab Disord, 2020,21(1):45-56.
[12]中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)[J]. 中华内分泌代谢杂志,2021,37(4):311-398.
[13]Bonnet F, Ducluzeau P H, Gastaldelli A, et al. Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women[J]. Diabetes, 2011,60(6):1660-1667.
[14]Najjar S M, Perdomo G. Hepatic insulin clearance: mechanism and physiology[J]. Physiology (Bethesda), 2019,34(3):198-215.
[15]Yada T, Damdindorj B, Rita R S, et al. Ghrelin signalling in β-cells regulates insulin secretion and blood glucose[J]. Diabetes Obes Metab, 2014,16 (Suppl 1):111-117.
[16]Lin Y, Liang Z, He L, et al. Gut ghrelin regulates hepatic glucose production and insulin signaling via a gut-brain-liver pathway[J]. Cell Commun Signal, 2019,17(1):8.
[17]Tokarz V L, MacDonald P E, Klip A. The cell biology of systemic insulin function[J]. J Cell Biol, 2018,217(7):2273-2289.
[18]Fluitt M B, Gambhir K K, Nunlee-Bland G, et al. Fasting plasma ghrelin levels are reduced, but not suppressed during OGTT in obese African American adolescents[J]. Ethn Dis, 2013,23(4):436-440.
[19]Barber T M, Casanueva F F, Karpe F, et al. Ghrelin levels are suppressed and show a blunted response to oral glucose in women with polycystic ovary syndrome[J]. Eur J Endocrinol, 2008,158(4):511-516.
[20]Flanagan D E, Evans M L, Monsod T P, et al. The influence of insulin on circulating ghrelin[J]. Am J Physiol Endocrinol Metab, 2003,284(2):313-316.