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
