Total Short-term Variability in Biomarkers of Hyperglycemia in Older Adults.

There is growing interest in the use of nontraditional short-term biomarkers of hyperglycemia [fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG)] to complement fasting glucose and hemoglobin A1c (Hb A1c) for prognosis and management of diabetes (1 ). Within-person variability in Hb A1c and fasting glucose has been previously characterized (2–4), but little is known about the variability of these alternative biomarkers of hyperglycemia in the general population. We quantified the 6-week total variability in fructosamine, glycated albumin, and 1,5-AG in older adults with and without diabetes and compared it to that of fasting glucose and Hb A1c. We included 153 participants from the Atherosclerosis Risk in Communities (ARIC) Study (5) who attended the initial visit-5 exam (2011– 13), returned for a second visit scheduled 4–8 weeks later, had complete data, fasted 8 h at both visits, and did not have outlying values. Institutional review boards approved all procedures, and all study participants provided written informed consent. Serum fructosamine, glycated albumin, and 1,5-AG were measured with the Roche Cobas 6000 (Roche Diagnostics). Fructosamine was measured with a colorimetric method (Roche Diagnostics). Glycated albumin (Asahi Kasei Lucica GA-L) and 1,5-AG (GlycoMark) were measured with enzymatic methods. Glucose was measured in plasma with an Olympus 480 analyzer (Beckman Coulter) and a hexokinase method. Hb A1c was measured in whole blood with HPLC (Tosoh G7, Tosoh Medics) standardized to the Diabetes Control and Complications Trial assay. Interassay CVs were 3.2% for fructosamine at a mean concentration of 220.3 mol/L, 4.4% for glycated albumin at 0.45 g/dL, 0.9% for 1,5-AG at 18.0 g/mL, 2.7% for glucose at 121.7 mg/dL, and 1.9% for Hb A1c at 5.36%. Analyses were conducted separately in those with and without diagnosed diabetes. For each biomarker, we calculated means by diabetes status: the mean at the original exam, the mean at the second exam, and the mean difference (second minus original). To partition the total variance of the repeated measurements into the between-subject variance ( BS 2 ) and within-subject variance ( WS 2 ),weused linearmixed-effects models with each biomarker as the dependent variable and the participant as a random effect. We calculated the between-person CV (CVG):