Associations of Alternative Markers of Glycemia with Hemoglobin A1c and Fasting Glucose

Abstract

BACKGROUND 1,5-anhydroglucitol (1,5-AG), fructosamine, and glycated albumin are of increasing interest as alternative measures of hyperglycemia. We characterize the associations of these nontraditional glycemic markers with hemoglobin A1c (HbA1c) and fasting glucose and assess their ability to identify people with diabetes. METHODS We conducted a cross-sectional comparison of 1,5-AG, fructosamine, and glycated albumin with HbA1c and fasting glucose measurements in 1,719 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Non-linear relationships were evaluated using R2 and F-statistics. Performance for identifying cases of diabetes was determined using the Area Under the Curve (AUC). Diabetes was defined by HbA1c ≥6.5%, fasting glucose ≥126 mg/dL (≥6.99 mmol/L), and/or a self-reported history of diagnosed diabetes. RESULTS Median values of HbA1c and fasting glucose were 5.8% and 109 mg/dL (6.05 mmol/L), respectively; 17.3% of the study population had diagnosed diabetes. Glycated albumin, fructosamine, and 1,5-AG were more strongly correlated with HbA1c compared with fasting glucose (all P-values <0.05). Nonlinear models provided the best fit for describing the relationships of the alternative markers to HbA1c. When diabetes was defined by an HbA1c≥6.5%, fructosamine (AUC 0.83; 95% CI: 0.79–0.87) and glycated albumin (AUC 0.87; 95% CI: 0.83–0.90) performed comparably to fasting glucose (AUC 0.83; 95% CI: 0.79–0.87), while 1,5-AG performed worse (AUC 0.74; 95% CI: 0.69–0.78) for identifying cases of undiagnosed diabetes. CONCLUSIONS Fructosamine and glycated albumin may be useful adjuncts to HbA1c and fasting glucose. Future studies should examine these markers in situations where fasting glucose or HbA1c measurements are invalid or not available.

Metrics Beyond Hemoglobin A1C in Diabetes Management: Time in Range, Hypoglycemia, and Other Parameters

“…38,39 An important limitation to the use of glycated proteins is the lack of established clinical cut points, standardization, and data on frequency of measurements in clinical practice. Efforts have been made to estimate values similar to A1C levels, [40][41][42][43][44][45] however, clinical targets continue to be unclear. Glucose being the main energy source has many redundant regulation mechanisms, and its clinical interpretation requires the understanding that glycemia is a dynamic process, which is a limitation true to all glycated proteins, including A1C.…”

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE

“…Apart from its role in pathogenesis, AGE-modified HSA (AGE-HSA) has been suggested as an alternative diagnostic marker to glycated hemoglobin (HbA1c) for monitoring glycemic status in diabetes (10). Although HbA1c is considered the "gold standard" marker, reflecting the glycemic status over the period of 8 -10 weeks (1, 10), factors like anemia, blood loss, splenomegaly, and iron deficiency affect HbA1c levels (11).…”

Comparing Multiple Measures of Glycemia: How to Transition from Biomarker to Diagnostic Test?

“…In this issue of Clinical Chemistry, Juraschek et al describe their study of the relationships of fructosamine, glycated albumin, and 1,5-AG to Hb A 1c and the fasting glucose concentration in a communitybased cohort (9 ). The authors report that nonlinear equations best fit the relationship of fructosamine and glycated albumin with both Hb A 1c and fasting glucose, albeit with considerable scatter.…”