| 1,5-Anhydroglucitol | |
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(2R,3S,4R,5S)-2-(Hydroxymethyl)oxane-3,4,5-triol |
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Other names
1-Deoxy-D-glucose; 1-Deoxy-D-glucopyranose; 1,5-Anhydro-D-glucitol; 1,5-Anhydrosorbitol; Aceritol; Polygalytol; 1,5-AG |
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| Identifiers | |
| CAS number | 154-58-5 |
| PubChem | 64960 |
| ChemSpider | 58485 |
| ChEBI | CHEBI:16070 |
| ChEMBL | CHEMBL344637 |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C6H12O5 |
| Molar mass | 164.16 g mol−1 |
| (verify) (what is: /?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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| Infobox references | |
1,5-Anhydroglucitol, also known as 1,5-AG, is used primarily 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, and once ingested is almost 100% non metabolized. 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 can assist diabetic patients in determining if their blood glucose levels are frequently above 180 mg/dL, even in the presence of relatively good hemoglobin A1c levels or blood glucose monitoring.
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The role of 1,5-AG was first inferred by Akanuma in 1981 [1] when he demonstrated decrease 1,5-AG levels in diabetic patients compared to non diabetic people. This observation was enhanced in 1983 when it was seen that 1,5-AG values fell to undetectable plasma levels in diabetic patients who did not receive insulin treatment,[2] yet those patients who were receiving treatment had detectable levels of 1,5-AG. Further studies[3] showed that patients who were receiving medication to lower their blood glucose had improvement in 1,5-AG levels. Once medication was discontinued, 1,5-AG decreased to pre-treatment levels, showing a significant difference from patients who maintained therapy. In 2003, 1,5-AG began to be looked at by researchers in the United States and was shown to be a valuable short-term glycemic monitor.[4][5] In 2006, 1,5-AG showed its most compelling clinical use when it was demonstrated that GlycoMark, an exclusive assay for postprandial hyperglycemia, was able to differentiate two patients who had similar, near goal, Hemoglobin A1c values, yet very different glucose profiles as shown by continuous blood glucose monitoring.[6] GlycoMark was able to distinguish between a patient having excessive glycemic variability, and one who was not, information which was not reflected in the hemoglobin A1c values.
The GlycoMark assay measures blood levels of 1,5-anhydroglucitol. 1,5-AG is found in nearly all foods and is ingested during the course of a regular diet. Once ingested, 1,5-AG 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 non diabetic people as well as people with diabetes 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 attempts to re-absorb as much glucose from the kidney back into the blood. Any glucose that can not be re-absorbed is excreted in the urine in a process known as glucosuria. During times of glucosuria, the additional amount of 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. Due to the lack of 1,5-AG being re-absorped, 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 GlycoMark to accurately reflect any hyperglycemic episodes over 180 mg/dL
The GlycoMark assay was developed by Nippon Kayaku, Inc. and is exclusive sold by GlycoMark, Inc. within the United States as well as Europe and Israel. GlycoMark can be run on almost any open chemistry analyzer, including those found in physician office laboratories. Two reactions take place during the measurement of GlycoMark. A comprehensive evaluation of the GlycoMark assay has been described in the literature.[7]
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.
GlycoMark results are expressed in a numerical form in mcg/mL. Due to the physiology of 1,5-AG, lower values of serum GlycoMark indicate worsening glucose control, with more frequent and prolonged glucose values over 180 mg/dL. A GlycoMark value of 10mcg/mL correlates to an average post meal glucose of 185 mg/dL, and represents the target value in people with diabetes. Values exceeding 10mcg/mL do not appear to provide additional clinically relevant information other than the knowledge that glucose values, on average are below 180 mg/dL. People with diabetes, who have GlycoMark values above 10mcg/ml may consider testing GlycoMark at a minimum of every 3 months, coinsiding with their hemoglobin A1c testing. People who have GlycoMark values below 10mcg/mL could benefit from nutritional counseling as well as certain medications which target post meal glucose spikes, such as pramlintide, exenatide, sitagliptin, saxagliptin, repaglinide or rapid acting insulins.
| GlycoMark (mcg/mL) |
Approximate Mean Postmeal Maximum Glucose (mg/dL) |
|---|---|
| >12 | <180 |
| 10 | 185 |
| 8 | 190 |
| 6 | 200 |
| 4 | 225 |
| <2 | >290 |
GlycoMark 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.