1,5-anhydroglucitol monitoring in diabetes: a mass balance perspective.

1,5-anhydroglucitol (AG) is a nonmetabolizable glucose analogue found in plasma due to ingestion. The normal steady-state concentration can be dramatically decreased by inhibition of tubular reabsorption during periods of hyperglycemia. For this reason, monitoring of AG has been plausibly advocated for detection of periodic glucosuric hyperglycemia. In this review, we examine the influence of variation in factors affecting both steady-state and transient changes in plasma AG. Among normals, the lower and upper limits of the plasma AG reference range vary by a factor of 5. Using a simplified mass balance model (a single compartment model with 3-6x larger-than-plasma volume of distribution), reasonable inter-individual variations of ingestion rate, glomerular filtration rate and fractional post-filtration reabsorption are each able to account for the wide range of normal, steady-state AG concentrations. In monitoring of changes in AG, inter-individual variations in the threshold for glucose excretion, volume of distribution and glomerular filtration rate are all likely to significantly affect correspondence of integral changes in AG to integral glucosuria/hyperglycemia. This combination of variables, affecting both steady-state and transient changes, is significantly confounding with respect to interpretation of serial plasma AG concentrations. Resolution of information content of AG monitoring is thus largely that of crossing simple characterization of deltas [+,0,-] for changes in AG concentration against the information content of hemoglobin A1c monitoring. Despite this limitation, AG monitoring can in principle provide information about glycemic control in the short term that is not apparent through monitoring of hemoglobin A1c alone. However, whether AG monitoring can lead to improved outcomes in diabetes management remains to be established.