1,5-anhydroglucitol in diabetes: Its role in diagnostics, screening, glycemic status assessment, and the prediction of complications

Abstract

1,5-anhydroglucitol (1,5-AG) is a short-term indicator of glycemic status, reflecting hyperglycemic glucose excursions over the prior 1-2 weeks. As glucose level remains in the normal range, plasma concentration of 1,5-AG is maintained stable due to the balance between intake with the food and renal excretion. Under hyperglycemic conditions, when the renal threshold for glucose is exceeded, concentration of 1,5-AG decreases due to competitive inhibition of 1,5-AG reabsorption by glucose. In clinical practice, plasma 1,5-AG is used for retrospective assessment of postprandial glucose fluctuations in diabetic subjects with mild or moderate elevation of HbA1c. The marker is also applied in clinical trials of new agents affecting postprandial glycemia. The advantages of 1,5-AG as a marker of glycemic status are stability, independence on the physiological state when sampling, applicability for patients with abnormalities of hemoglobin and lifespan of erythrocytes. Meantime, the value of this marker is limited in subjects with renal tubular acidosis, 4-5 stages of chronic kidney disease, renal glucosuria, in those receiving acarbose and SGLT2 inhibitors. Application of 1,5-AG for the diagnosis and screening of type 2 diabetes, gestational diabetes and prediabetes has been tested. It was revealed that sensitivity of 1,5-AG as screening tool may be insufficient in individuals with mild hyperglycemia, especially if fasting hyperglycemia prevails. Therefore, it has been proposed to combine 1,5-AG with assessment of fasting glucose for the screening purposes. In type 2 diabetic subjects low plasma 1,5-AG is a predictor of renal failure, cardiovascular events, including ischemic heart disease, heart failure and stroke. Decreased 1,5-AG concentration in pregnant women is a risk factor for gestational diabetes and macrosomia. Chromatography and enzymatic methods are used to determine 1,5-AG in blood, urine and other biological fluids. Currently, the relatively high cost and lack of standardization restrain the use of 1,5-AG in clinical practice. Further studies are needed for estimation of 1,5-AG value as a marker of glycemic status in type 1 diabetes, in patients with different levels of HbA1c and different magnitude of glucose variability, as well as in situations where the clinical value of HbA1c is limited.