Zelnick Leila R, Batacchi Zona O, Ahmad Iram, Dighe Ashveena, Little Randie R, Trence Dace L, Hirsch Irl B, de Boer Ian H
Kidney Research Institute, University of Washington, Seattle, WA
Division of Nephrology, University of Washington, Seattle, WA.
Diabetes Care. 2020 Oct;43(10):2379-2387. doi: 10.2337/dc20-0915. Epub 2020 Aug 11.
In chronic kidney disease, glycated albumin and fructosamine have been postulated to be better biomarkers of glycemic control than HbA. We evaluated the accuracy, variability, and covariate bias of three biomarkers (HbA, glycated albumin, and fructosamine) compared with continuous glucose monitoring (CGM)-derived measurement of glycemia across estimated glomerular filtration rate (eGFR) in type 2 diabetes.
A prospective cohort study was conducted of 104 participants with type 2 diabetes, 80 with eGFR <60 mL/min/1.73 m (not treated with dialysis) and 24 frequency-matched control subjects with eGFR ≥60 mL/min/1.73 m. Participants wore a blinded CGM for two 6-day periods separated by 2 weeks, with blood and urine collected at the end of each CGM period. HbA, glycated albumin, and fructosamine were measured by high-performance liquid chromatographic, enzymatic, and colorimetric nitroblue tetrazolium methods, respectively.
Within-person biomarker values were strongly correlated between the two CGM periods ( = 0.92-0.95), although no marker fully captured the within-person variability of mean CGM glucose. All markers were similarly correlated with mean CGM glucose ( = 0.71-77). Compared with mean CGM glucose, glycated albumin and fructosamine were significantly biased by age, BMI, serum iron concentration, transferrin saturation, and albuminuria; HbA was underestimated in those with albuminuria.
Glycated albumin and fructosamine were not less variable than HbA at a given mean CGM glucose level, with several additional sources of bias. These results support measuring HbA to monitor trends in glycemia among patients with eGFR <60 mL/min/1.73 m. Direct measurements of glucose are necessary to capture short-term variability.
在慢性肾脏病中，糖化白蛋白和果糖胺被认为是比糖化血红蛋白（HbA）更好的血糖控制生物标志物。我们评估了三种生物标志物（HbA、糖化白蛋白和果糖胺）与通过连续血糖监测（CGM）得出的血糖测量值相比的准确性、变异性和协变量偏差，该评估针对2型糖尿病患者的估计肾小球滤过率（eGFR）进行。
对104名2型糖尿病患者进行了一项前瞻性队列研究，其中80名患者的eGFR<60 mL/min/1.73 m²（未接受透析治疗），24名频率匹配的对照受试者的eGFR≥60 mL/min/1.73 m²。参与者佩戴盲法CGM设备两个为期6天的时间段，中间间隔2周，在每个CGM时间段结束时采集血液和尿液样本。HbA、糖化白蛋白和果糖胺分别通过高效液相色谱法、酶法和比色硝基蓝四唑法进行测量。
尽管没有一种标志物能完全捕捉个体内平均CGM血糖的变异性，但两个CGM时间段内个体的生物标志物值之间具有很强的相关性（相关性系数=0.92-0.95）。所有标志物与平均CGM血糖的相关性相似（相关性系数=0.71-0.77）。与平均CGM血糖相比，糖化白蛋白和果糖胺受年龄、体重指数、血清铁浓度、转铁蛋白饱和度和蛋白尿的显著影响而产生偏差；HbA在有蛋白尿的患者中被低估。
在给定的平均CGM血糖水平下，糖化白蛋白和果糖胺的变异性并不低于HbA，且存在其他多种偏差来源。这些结果支持在eGFR<60 mL/min/1.73 m²的患者中测量HbA以监测血糖趋势。直接测量血糖对于捕捉短期变异性是必要的。
