1,5-ANHYDROGLUCITOL, - MEASUREMENT OF GLYCEMIC VARIABILITY

1,5-ANHYDROGLUCITOL, - MEASUREMENT OF GLYCEMIC VARIABILITY 

1,5-Anhydroglucitol, also known as 1,5-AG, can be used to identify glycemic variability in people with diabetes who have normal or near normal hemoglobin A1c levels. 1,5-Anhydroglucitol is a naturally occurring monosaccharide found in nearly all foods, 1,5-Anhydroglucitol values decrease during times of hyperglycemia above 180 mg/dL, and return to normal levels after approximately 2 weeks in the absence of hyperglycemia.

Monitoring 1,5-anhydroglucitol in people with either type-1 or type-2 diabetes mellitus could be used to determine if blood glucose levels are frequently above 180 mg/dL, even in the presence of relatively good hemoglobin A1c levels or blood glucose monitoring. Despite this possible use and its approval by the FDA, 1,5-AG tests are rarely ordered. There is some data suggesting that 1,5-AG values are useful to fill the gap and offer complementary information to HbA1c and fructosamine tests.

Underlying Mechanism

The assay measures blood levels of 1,5-anhydroglucitol. 1,5-AG is ingested from nearly all foods during the course of a regular diet. It is nearly 100% non metabolized and remains in a relatively constant amount in the blood and tissues. 1,5-AG is carried in the blood stream and filtered by the glomerulus, where it enters the kidney. Once in the kidney, 1,5-AG is re-absorbed back into the blood through the renal proximal tubule. A small amount, equal to the amount ingested, of 1,5-AG is released in the urine to maintain a constant amount in the blood and tissue. This process occurs in people who do not have their blood glucose values rising over 180 mg/dL.

When a diabetic person's blood glucose exceeds 180 mg/dL for any period of time, the kidney cannot re-absorb all glucose back into the blood. The rest is excreted in the urine (glucosuria). The additional glucose in the kidney blocks 1,5-AG from being re-absorbed into the blood and 1,5-AG is excreted in the urine at a higher rate then normal. Blood levels of 1,5-AG decrease immediately, and continue to decrease until glucose values go below 180 mg/dL. Once hyperglycemia is corrected, 1,5-AG begins to be re-absorped from the kidney back into the blood at a steady rate. If a person's glucose levels remain below 180 mg/dL for approximately 4 weeks, 1,5-AG will return to its normal levels.

It is this competitive inhibition of 1,5-AG from glucose which allows the assay to accurately reflect any hyperglycemic episodes over 180 mg/dL

Analytical Specification

A comprehensive evaluation of the assay has been described in the literature.[8]

The assay can be run on almost any open chemistry analyzer, including those found in physician office laboratories. Two reactions take place during the measurement:

Reaction 1 is a pretreatment of the sample performed by adding glucokinase to convert glucose to glucose 6-phosphate in the presence of adenosine triphosphate, pyruvate kinase, and phosphoenol pyruvate. The purpose of this step is to alter glucose, which is found in the blood sample, so that it can not react during reaction 2.

Reaction 2 uses pyranose oxidase to oxidize the second hydroxyl of 1,5-AG, generating hydrogen peroxide. The amount of hydrogen peroxide is detected by colorimetry using peroxidase, and is in direct relationship to the serum 1,5-AG concentration.

Interpretation of Results

Results are in µg/mL. Lower values indicate worsening glucose control, with more frequent and prolonged glucose values over 180 mg/dL. 10 µg/mL of 1,5-AG correlates to an average post meal glucose of 185 mg/dL, and is the target value in people with diabetes. Values over 10 µg/mL indicate glucose on average is below 180 mg/dL. Those with values below 10 µg/mL could benefit from nutritional counseling, and medications which target post meal glucose spikes, such as pramlintide, exenatide, sitagliptin, saxagliptin, repaglinide or rapid acting insulins.

GlycoMark (µg/mL)	Approximate Mean Postmeal Maximum Glucose (mg/dL)
> 12	< 180
10	185
8	190
6	200
4	225
< 2	> 290

Indications and Use

The test is cleared by the FDA to be sold and marketed for the intermediate term monitoring of glycemic control in people with diabetes. GlycoMark is available through most major reference laboratories, including Quest Diagnostics and Labcorp or may be performed in a hospital or physician's office