糖化白蛋白 (GA) 是用于糖尿病患者血糖控制的中期(前2~3周)血糖监测指标。旭化成制药株式会社现已开发出 Lucica® GA-L——一种采用独特的酶法测定糖化白蛋白的液体试剂,并已获得美国食品药品监督管理局 (FDA) 的批准。
糖化白蛋白 (GA) 是血清白蛋白糖基化的产物,其定义为含有与葡萄糖结合的赖氨酸残基的白蛋白(糖化赖氨酸)。
白蛋白是人类血液中最丰富的蛋白质。
人类血清白蛋白含有 59 个赖氨酸残基 (Lys)。其中4个赖氨酸残基 (Lys) 是发生糖基化的主要位点。1
1)Iberg N and Flückiger R, J Biol Chem. 1986;261(29):13542-5.
糖化白蛋白反映的是之前2~3周的血糖状况,因为糖化白蛋白的半衰期约为 17 天。2
2)Tahara Y and Shima K, Diabetes Care. 1995;18(4):440-7.
在接受降糖治疗的 30 例患者中(在美国进行的多中心前瞻性研究),在第 4 周时糖化白蛋白的变化与在第 12 周时 A1C 的变化一致。3
3) Desouza CV, et al., Endocr Pract. 2015 Nov;21(11):1195-203.
在 24 周的前瞻性研究中,在两次研究访视之间,糖化白蛋白与下述各项变化一致(同向增加或减少):与平均血糖 (MBG) 变化一致率 60.8%、与果糖胺变化一致率 55.5%,与A1C 变化一致率 45.5%。4
Design: 24-week prospective study of assay performance. Eight US clinics.
Subjects: Type 1 (n = 73) and type 2 diabetes (n = 77) undergoing changes to improve glycemic control (n = 98) or with stable diabetes therapy (n = 52).
Interventions: GA, fructosamine, and A1C measured at prespecified intervals. Mean blood glucose (MBG) calculated using weekly self-monitored blood glucose profiles.
4) Desouza CV, et al., J Clin Endocrinol Metab. 2020 Mar 1;105(3).
Desouza CV, et al., Results of a Study Comparing Glycated Albumin to Other Glycemic Indices. https://doi.org/10.1210/clinem/dgz087
©2019 Desouza CV, et al. ; licensee Oxford University Press
Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)
果糖胺是一个通用术语,是指血清中所有糖化血清蛋白,包括糖化白蛋白。Lucica® GA-L 可选择性地测量糖化白蛋白。果糖胺检测法测量的是糖化血清蛋白的总浓度,测量值会由于急性系统性疾病或肝病而发生波动。但是,糖化白蛋白检测法(例如 Lucica® GA-L)测量的是糖化白蛋白与总白蛋白的比率,从而最大程度地减少了糖化和非糖化白蛋白浓度的干扰。
由于糖化白蛋白是通过人血清白蛋白的糖基化产生的,因此它不会受到红细胞寿命改变的病理因素影响,例如肾性贫血、透析或促红细胞生成素治疗、缺铁性贫血或缺铁性贫血恢复期。
另一方面,有必要注意白蛋白代谢改变的病症。
✔ | 相对于血糖水平而言,糖化白蛋白水平偏高的病症 白蛋白代谢速度减慢的疾病:甲状腺功能减退4、肝硬化5以及消瘦6 |
✔ | 相对于血糖水平而言,糖化白蛋白水平偏低的病症 白蛋白代谢速度加快的疾病:甲状腺功能亢进4、糖皮质激素治疗7、库兴氏综合征8、肾病9以及晚期肥胖10 |
5) Koga M, et al., Diabetes Res Clin Pract. 2009 May;84(2):163-7.
6) Miyamoto H, et al., Rinsho Byori. 2008 Sep;56(9):761-6. Japanese.
7) Koga M, et al., Clin Chim Acta. 2007 Mar;378(1-2):48-52.
8) Iizuka K, et al., BMJ Case Rep. 2016 Mar 9;2016 pii: bcr2016214788
9) Kitamura T, et al., Clin Chim Acta. 2013 Sep 23;424:164-7.
10) Okada T, et al., Intern Med. 2011;50(1):23-9.
11) Koga M, et al., Clin Chim Acta. 2015 Jan 1;438:19-23.
糖尿病患者(血液透析/肾功能正常的病例)中随机血糖与糖化白蛋白之间的关系(日本)
✔ | 患有糖尿病的血液透析患者 (B) 的 HbA1c 水平明显低于未患有慢性肾功能衰竭 (CRF) 的糖尿病患者 (D) 的 HbA1c 水平。 |
✔ | 患有糖尿病的血液透析患者 (A) 的糖化白蛋白水平 与未患有慢性肾功能衰竭 (CRF) 的糖尿病患者 (C) 的糖化白蛋白水平几乎相同。 |
✔ | 糖化白蛋白是评估糖尿病血液透析患者血糖控制效果的有效指标。 |
〇 | Hemodialysis (HD) patients with diabetes |
〇 | Diabetic patients without chronic renal falure (CRF) |
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接受血液透析的糖尿病患者的 HbA1c 和血糖之间的回归斜率(0.012),相比未患有慢性肾功能衰竭 (CRF) 的糖尿病患者,明显更低(0.021;p < 0.001),而两组患者中糖化白蛋白和血糖之间的斜率没有明显差异(0.068 和 0.058;p > 0.10)。
Used with permission of American Society of Nephrology, from Glycated Albumin Is a Better Glycemic Indicator Than Glycated Hemoglobin Values in Hemodialysis Patients With
Diabetes: Effect of Anemia and Erythropoietin Injection, M inaba et al., 18(3), 2007; permission conveyed through Copyright Clearance Center, Inc.
✔ | In a four-year follow-up study, the Kaplan-Meier method indicated a lower mortality risk in the GA <20% group than other groups ( GA 20.0-24.5% and GA >24.5% groups) in 108 hemodialysis patients with diabetes without a history of CVD. No significant differences were noted in the survival rate in 70 cases with a history of CVD. |
Inaba M, et al. Impact of atherosclerosis on the relationship of glycemic control and mortality in diabetic patients on hemodialysis Clin Nephrol 2012. 78 (4), 273-80.
“Best Practice for Diabetic Patients on Hemodialysis 2012” 由日本透析治疗学会 (Japanese Society for Dialysis Therapy) 发布,在其“血糖控制目标声明”中给出了以下说明。
✔ | Pre-dialysis casual plasma glucose and glycated albumin (GA) levels are recommended as indicators for glycemic control. |
✔ | The hemoglobin A1c (HbA1c) level might be used only as a reference, because the HbA1c level decreases in the presence of anemia or erythropoiesis-stimulating agents (ESAs) and may not accurately represent glycemic control in hemodialysis patients. |
✔ | Pre-dialysis casual plasma glucose levels (or 2-h postprandial plasma glucose levels) <180–200 mg/dL |
✔ | For hemodialysis patients, GA levels <20.0% are recommended |
✔ | For hemodialysis patients with a history of cardiovascular events and who have hypoglycemic episodes, GA levels <24.0% are suggested. *Further studies are required to definitively determine target values. |
Nakao T. et al., Best practice for diabetic patients on hemodialysis 2012.Ther Apher Dial. 2015 Mar;19 Suppl 1:40-66.
糖化白蛋白不易受母体铁代谢的影响,因此可用于确认妊娠期严格的血糖控制情况。
Hiramatsu Y et al., Endocr J. 2012(59):145-151
详见以下报告:
1) Sugawara D. et al., “Glycated albumin level during late pregnancy as a predictive factor for neonatal outcomes of women with diabetes.” J Matern Fetal Neonatal Med 2018 (15):2007-2012
2) Li HP. et al., “Association between glycemic control and birthweight with glycated albumin in Chinese women with gestational diabetes mellitus.” J Diabetes Investig 2016 Jan;7(1):48-55.