GlycoMark History

The association of 1, 5 anhydroglucitol with insulin-dependent diabetes mellitus (IDDM) was inferred in a study by Akanuma et al. in 1981 (Decreased plasma 1,5-anhydroglucitol in diabetic patients. Diabetes 1981; 30 suppl. 1:124A). This study demonstrated decreased 1,5-AG in diabetic patients compared to normal individuals. This observation was enhanced in 1983 when Yoshioka et al. (Variations of 1-deoyglucose (1,5-anhydroglucitol content in plasma from patients with insulin-dependent diabetes mellitus. Clin. Chem 1983;29:1396-8) noted that 1,5-AG fell to undetectable plasma levels in diabetic patients who did not receive insulin treatment. 1,5-AG was detectable in patients receiving treatment. Dr. Yoshioka proposed that 1,5-anhydroglucitol was involved in diabetic metabolism; however, it is now known that his method for measuring 1,5-AG (GL-LC) was insensitive to 1,5-AG levels in untreated diabetic patients.

These early studies were followed with more sensitive assays developed for 1,5-anhydroglucito. Yamanouchi et al. (Plasma 1,5 anhydroglucitol as new clinical marker of glycemic control in NIDDM patients. Diabetes 1989;38:6:723-9) followed patients whose diabetes was controlled by a variety of therapies for up to twelve months. They measured 1,5-AG, hemoglobin A1c (HbA1c) and fasting plasma glucose and discovered that over time HbA1c decreased with concomitant increases in 1,5- anhydroglucitol.

In 1996, Yamanouchi et al. (Clinical usefulness of serum 1,5-anhydroglucitol in monitoring glycemic control. The Lancet 1996; 347:1514-8) published a longitudinal study of patients with type 2 diabetes who received anti-hyperglycemic therapies. Following four weeks of therapy all of the patients showed an improvement (increase) in 1,5-AG serum levels. When therapy was discontinued in half of the patients, 1,5-AG decreased significantly to pre-treatment levels. At six weeks there was a significant difference between the discontinued group and the half that continued on anti-hyperglycemic therapy.

The 1996 Yamanouchi et al. study demonstrated that 1,5-AG changes more rapidly and significantly (within a one to two week moving window) to glycemia than either fructosamine (2-3 weeks) or HbA1c (2-3 months). The GlycoMark assay has been used in Japan primarily for short-term glycemic control, a utility confirmed by McGill et al. Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia. Diabetes Care. 2004; 27:8:1859-64) in a U.S. study.

In 2006, Dungan J, Buse J et al. (1,5-Anhydroglucitol and Postprandial Hyperglycemia as Measured by Continuous Glucose Monitoring System in Moderately Controlled Patients with Diabetes. Diabetes Care. 2006; 29:6:1214-1219) demonstrated that GlycoMark is also a sensitive and apparently exclusive assay for postprandial hyperglycemia. Whereas HbA1c and fructosamine average both hypo- and hyperglycemia over a longer timeframe GlycoMark targets only hyperglycemia (glycemia occurring above the renal threshold). They showed in two patients that, whereas HbA1c showed similar near normal values, GCMS monitoring indicated one was not in good control and this was reflected in his abnormal GlycoMark level.

Recent studies on anti-hyperglycemic drug efficacy have demonstrated that GlycoMark is the most effective marker for glycemic improvement during therapy. These and many of the above studies are available on this web site.