Faculty Peer Reviewed
Hemoglobin A1 (Hb A1c) is the standard method for monitoring diabetic patients’ long-term glycemic control by indicating average blood glucose levels over a period of two months, or half of the average life span of red blood cells. A new biochemical marker GlycoMarkTM is a test that measures serum levels of 1,5-anhydroglucitol (1,5-AG), a monosaccharide derived from ingestion of food, slightly different in structure from glucose. The test has been available in Japan since the early 1990s but was only recently approved by the FDA for intermediate-term monitoring of glycemia. It is becoming increasingly available in diagnostic laboratories. Much of the original data on the use of this test come from Japan; these studies have been repeated in the United States to demonstrate the applicability of those findings to the more heterogeneous American population of both type 1 and 2 diabetics. In these studies, the results with 1,5-AG testing were compared to the current gold standard of Hb A1c.
In normals, the rate of intake of 1,5-AG is matched by the daily excretion rate such that serum levels and urinary excretion of 1,5-AG remain constant. Renal reabsorption is 99.9% and is competitively inhibited by excessive excretion of urinary glucose. Therefore, in diabetes with hyperglycemia and glucosuria, the serum levels of 1,5 AG fall and are inversely proportional to the degree of hyperglycemia. This is because the high levels of glucose block reabsorption of 1,5-AG in the proximal tubule, causing increased urinary excretion and hence decreased 1,5-AG levels in the serum. In the 1980s, Yoshioka et al. demonstrated its utility in monitoring glycemic control by showing that reduced concentrations of 1,5-AG are present in the serum of hyperglycemic patients (2).
Random glucose measurements provide a “snapshot” of circulating glucose levels but provide no information about the consistency of glycemic control. 1,5-AG is a marker that responds to changes in glycemia over the course of weeks as opposed to months, a feature that may aid modification of therapy. Studies have shown changes in circulating levels within 24 hours and significant responses in 1,5-AG levels after two weeks of treatment (3).
Controlling postprandial hyperglycemia is a critical component of diabetes management in the prevention of cardiovascular complications. There is some evidence to suggest that postprandial glucose may be an independent risk factor for the development of macrovascular complications (4). Postprandial glycemic levels have been difficult to monitor, but 1,5-AG levels have proven to be beneficial for this purpose.
Dungan et al. showed that GlycoMark revealed significantly different post-meal glucose levels in patients with similar A1c levels, suggesting that A1c alone does not give a complete picture of glycemic control. Using a continuous glucose monitoring system, Dungan et al. showed that in suboptimally controlled diabetic patients, the use of 1,5-AG correlated most closely with mean postmeal maximum glucose (4).
The utility of GlycoMark as a clinical tool lies in two distinct clinical circumstances: monitoring short-term glucose control over a course of 1-2 weeks and as a measure of postprandial hyperglycemia in patients with at least moderately controlled diabetes (Hb A1c <8%). In such patients, 1,5-AG levels can be used to measure the degree to which postmeal glucose levels rise above the renal threshold for glucosuria (normally 180 mg/dL). GlycoMark can best be viewed as a complementary tool to hemoglobin A1c to aid in the management of moderately controlled diabetics and to confirm that diabetics with A1c levels near target are not having excessive postprandial glucose excursions. Dungan et al. advocate the following strategy: “In clinical practice, A1c and 1,5-AG may be used sequentially, first utilizing the A1c assay to identify patients who are moderately or well controlled, and then using the 1,5-AG assay to determine the extent of postprandial glucose excursions” (4).
At the present time, GlycoMarkTM affords the practitioner the most accurate monitoring of glucose control in the short term, allowing for earlier interventions in lifestyle or medications to correct glycemic excursions. Its role in detecting postprandial hyperglycemia is somewhat more limited and is only appropriate for moderately controlled diabetic patients. It should also be noted that there are certain medical conditions that limit the accuracy of measuring 1,5-AG such as post-gastrectomy, pregnancy, end-stage renal disease (or other forms of chronic renal failure in which the renal threshold for glycosuria is altered), advanced cirrhosis, and those with persistent glucosuria.
Peer reviewed by Dr. Stephen B. Richardson, Associate Professor, NYU Division of Endocrinology
1. Buse JB, Freeman JL, Edelman SV, et al. Serum 1,5-anhydroglucitol (GlycoMark): a short-term glycemic marker. Diabetes Technol Ther 2003;5:355-363.
2. Yoshioka S, Saitoh S, Negishi C, et al. Variations of 1,5-anhydroglucitol content in plasma from patients with IDDM Clin Chem 1983;29:1396-1398
3. Yamanouchi T, Ogata N, Tagaya T, et al. Clinical usefulness of serum 1,5-anhydroglucitol in monitoring glycemic control. Lancet 1996;347:1514-1518.
4. Dungan KM, Buse JB, Largay 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;29:1214-1219.
5. McGill JB, Cole TG, Nowatzke W,et al. Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia: a U.S. trial of the GlycoMark assay. Diabetes Care 2004;27:1859-1865.