A kinetic mass balance model for 1,5-anhydroglucitol: applications to monitoring of glycemic control

Abstract

The polyol 1,5-anhydroglucitol (AG) present in human plasma is derived largely from ingestion and is excreted unmetabolized. Reduction of plasma [AG] has been noted in diabetics and is due to accelerated excretion of AG during hyperglycemia. Plasma [AG] has therefore been proposed as a marker for glycemic control. A precise understanding of its utility relies on a quantitative understanding of the mass balance for AG. In this study, non-steady-state data from the literature were analyzed to develop a dynamic mass balance model for AG that is based on the two-compartment model proposed by Yamanouchi et al. [T. Yamanouchi, Y. Tachibana, H. Akanuma, S. Minoda, T. Shinohara, H. Moromizato, H. Miyashita, and I. Akaoka. Am. J. Physiol. 263 ( Endocrinol. Metab. 26): E268—E273, 1992]. The data are consistent with a model in which exchange between tissue and plasma pools is rapid and in which the tissue compartment mass is two to three times the mass of the plasma compartment. According to model estimates, accelerated excretion of AG due to hyperglycemia can cause marked net depletion of total AG over a time scale of days. Recovery from a depleted state is slow because the total body capacity represents >5 wk of normal intake. Accordingly, AG monitoring should be able to indicate the presence of past glucosuric hyperglycemic episodes during a period of days to weeks, as well as provide information on the extent to which high deviations from the average plasma glucose concentration are operative.

Circulating 1,5-Anhydroglucitol Levels in Adult Patients With Diabetes Reflect Longitudinal Changes of Glycemia

“…Such depletion has been observed to occur in severe hyperglycemia as a result of persistent glucosuria (19). Additionally, a dynamic mass balance two-compartment model has been developed for 1,5AG (20), and it demonstrates that the tissue compartment is two to three times the mass of the plasma compartment. Model estimates suggest that accelerated depletion of 1,5AG is associated with slow recovery upon the initial improvement of glycemia, because the body pool of 1,5AG represents ϳ5 weeks of normal dietary intake.…”

Clinical Application of 1,5-Anhydroglucitol Measurements in Patients with Hepatocyte Nuclear Factor-1α Maturity-Onset Diabetes of the Young

“…Subsequently, 1,5-AG urinary excretion is increased during hyperglycemia, and it results in a lowered plasma concentration (4). This explains its low plasma level in patients with poorly controlled diabetes.…”

Evaluating the Role of Serum 1,5-Anhydroglucitol Concentrations as an Indicator of Hyperglycemic Changes in Diabetic and Non Diabetic Surgical Patients

“…It has been reported that the average daily increase in serum 1,5-AG concentrations is constant at about 0.3 μg/mL, and is not influenced by treatment, age, body weight, or duration of DM [20]. In addition, the normalization of 1,5-AG concentrations from depleted states has been believed to require approximately 5 weeks even under continuous normoglycemic conditions [20,21]. Thus, the recovery of 1,5-AG concentrations in our surgical patients may have been slow, with a time scale of several weeks after feeding is initiated.…”