Monitoring of glucose or glucose-related variables is of paramount importance in evaluating and adjusting glucose-lowering therapies. Self-monitoring of glood glucose (SMBG) and tests of glycated hemoglobin (A1C) levels allow measurement of fasting, timed or random glucose levels or estimates of mean glycemic exposure. There is however some evidence to suggest that control of glucose variability and post prandial glucose may be equally important in prevention of late complications, and there is therefore a need for additional tests to evaluate these aspects of glucose exposure.
1, 5 anhydroglucitol is a naturally occurring 1-deoxy form of glucose first identified in 1888 within the plant kingdom and in 1972 within humans. It circulates in the body mostly in its free form. When glucose levels surpass the renal threshold for glucosuria, 1,5 anhydroglucitol is excreted in the urine, thus lowering levels in serum or plasma. Poor glucose control is associated with low levels of 1, 5 anhydroglucitol (1, 5- AG). It can also reflect transient elevation of glucose over the previous 2-3 weeks.  This reflects changes in glycemic control on a shorter time scale than either A1C or fructosamine levels.
Image 1: Chemical structure of 1, 5 Anhydroglucitol
An assay is available and marketed as GlycoMark. The test is applicable to both serum and plasma samples. General normal ranges are from 11-24 mcg/ml. The assay has some limitations with individuals who have renal failure, Fanconi syndrome, liver disease (cirrhosis), those using a high soy diet or certain herbal medicines. However, it is unaffected by changes in hemoglobin, bilirubin or red blood cell life span which do affect the Hemoglobin A1C assay.
1,5 – AG has been considered potentially useful for monitoring glycemic excursions or glucose variability since it measures shorter-term changes in glycemic control than A1C or fructosamine. A1C measurement cannot differentiate between fasting and postprandial glucose levels.
Measurement of post-prandial glucose is considered important as a means of monitoring changes in diet and/or pharmacologic therapies. Since post-prandial glucose becomes an important contributor to glycemic control as A1C approaches 8%, and 1, 5-AG is a predictor of glycemic excursions, 1,5-AG could potentially offer an additional tool for assessing post-prandial glucose control. , 
Postprandial hyperglycemia is seen even in Type 1 patients with good glycemic control. A recent study among children with Type 1 DM indicated the utility of 1,5-AG in conjunction with A1C to evaluated therapy for DM and glucose control along with ability to target postprandial hyperglycemia.
According to various studies conducted, 1, 5-AG could serve to assist in evaluating glycemic control over shorter intervals than the 3 month response time of A1C. It could therefore provide earlier warning of worsening glycemic control and guide earlier therapeutic intervention. It is however unlikely that 1, 5-AG could replace A1C and there are few data or studies to indicate that the test reflects risk of microvascular or macrovascular complications.
A study undertaken in 2008 compared the relationship between changes in A1C and 1,5-AG excursions. The INITIATE Study comprised 233 patients with Type 2 DM who were randomized to BIAsp 30 or Insulin Glargine (IGlar). Patients were also taking Metformin between 1500-2550 mg per day. Assays were performed at baseline, week 12 and week 28. Irrespective of the treatment arm, serum levels of 1,5-AG were strongly related to A1C levels. 1,5-AG levels fell during hyperglycemia and increase when glycemic control is reestablished. The suggestion is that 1,5-AG may be useful as an independent marker of glycemic control. Since 1,5-AG may have utility as a measure of short term glycemic changes, this may enable physicians to select and adjust therapeutic treatments to minimize glycemic variability.
Disparity in 1,5-AG levels
An additional concern with markers of glycemic control is disparities among ethnic groups.
The DURABLE trial conducted from 2005-2007 enrolled 2094 patients in 243 sites throughout the US, North America, Europe and Asia. It evaluated A1C and 1,5-AG among the various racial and ethnic groups. It was noted that non-Causcasian individuals has generally higher baseline A1C and more variability of 1,5-AG was seen in these groups, particularly Asian and African patients. Asian patients were noted to have higher 1,5-AG levels despite higher PPG (postprandial glucose) levels. Several etiologies have been proposed but none have been delineated at present. Possible de novo synthesis of 1,5-AG; differences in renal metabolism of 1,5-AG along with differences in diet all are being investigated.
A recent study in the US investigated racial disparities in glycemic markers was conducted in participants of the ARIC (Atherosclerosis Risk in Communities). A1C and 1,5-AG levels were measured in both white and black participants. The results indicate that black individuals has significantly higher A1C levels and lower 1,5-AG levels than white individuals. It was noted that fasting glucose concentrations were similar in both groups. Thus, the implication is that the disparities noted might be driven by the differences in nonfasting glycemia which is reflected in levels of 1,5-AG. Additional studies are needed for further delineate this disparity and its possible mitigating factors.
Glycomark and SGLT-2 Inhibtors
There is a potential interference with SGLT-2 Inhibitor therapy. Glycomark levels can be falsely low and its use in individuals utilizing this therapy must be carefully considered. Further studies are continuing.
At present, 1, 5- AG is not widely utilized. However as more clinical data is forthcoming with regard to its utility in determining glucose control and variability, its use may broaden.
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