The Transport And Metabolism Of 1,5-anhydroglucitol In Vivo And Its Diagnostic Value For Diabetes Screening

Objective: 1,5-Anhydroglucitol(1,5-AG)can not only accurately reflect glucose levels over a period of 1 to 2 weeks in diabetic patients but also have an advantage on reflecting postprandial hyperglycemia.Our recent studies on 1,5-AG levels demonstrated that unlike the marked decline in chronic hyperglycemia status,there was a slight increase in 1,5-AG levels after an acute glucose load or a steamed bread meal test.The current study aims to clarify the mechanism and to further evaluate the clinical value of serum 1,5-AG in diabetes screening in Chinese population.Methods: Firstly,the intra-and extra-cellular 1,5-AG concentrations of HepG2,C2C12 and mouse primary hepatocytes were examed to investigate the 1,5-AG transport and metabolism.In addition,the influence of an acute glucose load on the transport of 1,5-AG was studied.Secondly,a total of 3098 participants at high risk for diabetes(1467 men,1631 women)were enrolled.All participants underwent a 75 g oral glucose tolerance test(OGTT),and the fasting plasma glucose(FPG),2-h postload glucose(2hPG),glycated hemoglobin A1c(HbA1c)and serum 1,5-AG levels were measured.Diabetes were diagnosed based on the 2010 American Diabetes Associasion(ADA)criteria.Results:(1)The basic research part showed that:(1)The affinities of glucose oxidase(GOD)and hexokinase(HK)for 1,5-AG were 5% and 42.5% of that for glucose,respectively,and the Vmax of HK for glucose was 46 times greater than that for 1,5-AG;(2)1,5-AG is stable in vivo since there’s no de novo synthesis and rarely metabolized;(3)1,5-AG can enter and exit cells freely based on a concentration gradient to achieve a dynamic balance,and the intracellular concentrations of 1,5-AG was about 50–80% of the concentrations in the extracellular fluids;(4)An acute glucose load affects 1,5-AG transport and that the levels of 1,5-AG extracellular increased slightly,rather than declined;(2)And the clinical study part demonstrated that:(1)The mean 1,5-AG level in the diabetic group was significantly lower than that in non-diabetic group[12.5(7.8–17.5)μg/mL vs.20.5(15.3–26.4)μg/mL,P<0.001];(2)Receiver operating characteristic(ROC)analysis showed that the optimal cut-off point was 15.9μg/mL,for which the sensitivity,specificity,and area under the curve(AUC)were 69.2%,72.3%,and 0.781,respectively.For the combination of FPG and 1,5-AG,the sensitivity,specificity,and AUC improved to 82.5%,83.5%,and 0.912,respectively.This method helped 75.8%of the participants avoid an OGTT.Conclusions:1,5-AG was stable,as there was no de novo synthesis,and was not metabolized in vivo to any appreciable extent.Moreover,1,5-AG can be freely transported through intra-and extracellular spaces based on concentration gradients to achieve a dynamic balance.Furthermore,the optimal cut-off point for 1,5-AG to detect diabetes was15.9μg/mL.When combined with FPG,this method helped 75.8%of the participants avoid an OGTT,reducing the need to carry out the OGTT by 43.9%compared to the use of the FPG criterion only.