The GlycoMark Test – How It Works

A more complete picture of glycemic control.

The GlycoMark test is an FDA-cleared, non-fasting serum or plasma test for monitoring intermediate glucose control in people with diabetes. The GlycoMark test measures the 1,5-anhydroglucitol molecule in the blood.

As a specific indicator of recent hypoglycemic excursions, the GlycoMark test provides a clinically proven one- to two-week measure related to the average daily maximum blood glucose. It can be used along with other tests such as A1C anting glucose to provide a complete picture of glycemic control so that you can manage your patients’ diabetes more effectively.

The GlycoMark test works by monitoring 1,5-AG.

In diabetes, glucose levels can be persistently high, or they can fluctuate over time. These fluctuations can occur over weeks, days, or hours, depending on the level of glycemic control. When A1C levels start to approach therapeutic goals, this can indicate that fasting glucose is being well managed, but the patient may still be having episodes of hyperglycemia, sometimes referred to as glucose spikes or hyperglycemic excursions, following meals. A1C is a long-term average, and cannot distinguish between stable glucose levels and glycemic variability characterized by high glucose levels balanced by low levels. The offsetting effect of glucose highs and lows produces an A1C level that resembles that of a patient with a stable glucose level.

The GlycoMark test works by monitoring levels of the 1,5-anhydroglucitol (1,5-AG) molecule in the blood. In people who do not have diabetes, and those with diabetes who have well-controlled blood sugars, 1,5-AG is stored at a steady state in the tissues and the bloodstream, keeping blood levels high and producing a high GlycoMark score. 1,5-AG is structurally similar to glucose, and it is filtered in the kidneys like glucose. However, it is present in a concentration far lower than glucose.

The body’s response to uncontrolled hyperglycemia is to purge glucose through the urine. In fact, this is how diabetes was identified before modern laboratory tests were available. The blood level above which glucose is eliminated through urine is called the “renal threshold,” which is, on average, 180 mg/dL. In people with blood glucose spikes averaging over 180 mg/dL, 1,5-AG does not stay in the body as it should. As blood glucose rises, less 1,5-AG is found in the blood. This is reflected in lower GlycoMark test results. In this way, the 1,5-AG concentration is intimately tied to the renal threshold. Because 1,5-AG levels decrease when patients have hyperglycemia characterized by glucose levels higher than the renal threshold, 1,5-AG levels are also related to hyperglycemia. More specifically, 1,5-AG levels can provide insight into the average daily peak glucose levels, revealing information about hyperglycemia that can’t be uncovered by A1C alone.

*The ADA recommends a postprandial blood glucose goal of 180 mg/dL.


In people with diabetes with well-controlled blood glucose levels (less than 180 mg/dL), 1,5-AG is stable at high levels in the tissues and blood. This is because 1,5-AG is filtered through the kidneys and nearly all of it is reabsorbed back into the blood stream in the renal proximal tubules. So when blood glucose is well-controlled, 1,5- AG is kept in the body at high levels.

In people who have high blood sugars, exceeding approximately 180 mg/dL, there is too much glucose in the kidneys. Because the 1,5-AG levels are much lower than glucose levels, the excess glucose is preferentially reabsorbed in the renal proximal tubules, blocking 1,5-AG from being reabsorbed. Thus, 1,5-AG is excreted in the urine and decreases in the bloodstream. Decreased serum 1,5-AG produces a lower GlycoMark test result.

Because the  GlycoMark test is linked to the renal threshold and is affected by periods of hyperglycemia exceeding the renal threshold, it can provide an estimate of the average daily peak glucose level. When 1,5-AG levels are abnormal (e.g. below the reference range), the average daily peak glucose levels can exceed the renal threshold. When compared to estimated average glucose determined by A1C levels, a large difference between the estimated average daily peak glucose level and the estimated average glucose level may indicate glycemic variability – glucose highs balanced by lows – that should be further investigated.

The GlycoMark test: Accuracy and limitations.

Results for the GlycoMark test have been proven in more than 40 clinical studies conducted at hospitals and universities around the world. In those studies, GlycoMark has been studied in comparison to other measures of glucose control, including continuous glucose monitoring, oral glucose tolerance tests, A1C and fructosamine.

Although the GlycoMark test can help identify hyperglycemia producing estimated average daily glucose peak levels exceeding the renal threshold, it cannot provide information about the timing of high glucose levels or duration of hyperglycemic episodes. Hyperglycemia can occur in the fasting period, post-meal period, or both.

In addition, the GlycoMark test has been studied in various groups including people with type 1, type 2 and gestational diabetes and people with kidney disease.

  • The GlycoMark test is not affected by hemoglobinopathies, such as anemias, sickle cell disease or malaria because it is not a hemoglobin glycosylation marker like HbA1c.
  • The GlycoMark test can also be used as a short term (two-week) marker of glucose control at all levels of A1C, and can identify the degree/frequency of hyperglycemic excursions at A1Cs of 8% or less.

The GlycoMark test has been tested and found to be unaffected by hemoglobin (125 mg/dL), triglycerides (1153 mg/dL), bilirubin (40 mg/dL), glucose (1000 mg/dL),  maltose (500 mg/dL), ascorbic acid (25 mg/dL), uric acid (20 mg/dL), urea (20 mg/dL) and creatinine (10 mg/dL).

However, there are some conditions* that may interfere with the results of the GlycoMark test, which include the following:

  • Kidney Disease – The GlycoMark results are not accurate in advanced kidney disease (Stage 4 or 5; GFR below 30) or dialysis patients.
  • Liver Disease – Advanced cirrhosis of the liver may cause low GlycoMark results.
  • Pregnancy – GlycoMark results may run lower due to lower and varying renal thresholds during pregnancy.
  • Reduced Food Absorption – Reduced food absorption, as after gastrectomy, in celiac disease or use of the drug acarbose, may cause low GlycoMark values. Other α-glucosidase inhibitors have not been found to cause low results.
  • Glucose in the Urine – Persistently positive urine glucose levels in certain kidney conditions or use of diabetes agents called SGLT2 inhibitors (sodium-glucose transporter-2) such as INVOKANA® cause low GlycoMark values.
  • Steroid Use – Can cause hyperglycemia, which may result in expected low GlycoMark levels.
  • Intravenous Hyperalimentation and Chinese Medicines – Use of certain Chinese medicines (Polygala, Tenuifolia and Senega Syrup) may cause high GlycoMark values.

*Data on file. See package insert for details

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