The main finding of the present study was that vascular endothelial function parameter L_RHI correlates significantly with 1,5-AG in T2DM patients with HbA1c <8.0%.
In fact, 1,5-AG blood level correlate with postprandial hyperglycemia in patients with HbA1c <8.0%, in both type 1 diabetes mellitus  and T2DM . In addition, the use of CGM has demonstrated a significant correlation with MAGE and indices of postprandial hyperglycmia in patients with HbA1c <8.0% . 1,5-AG has been clinically used as a marker of changes in blood glucose level. Sakamoto et al.  used this parameter to compare changes in blood glucose level according to glucose-lowering therapy, similar to CGM data. Furthermore, since low 1,5-AG levels are associated with coronary artery disease, 1,5-AG has also been used to identify patients at high risk of cardiovascular disease . Furthermore, blood 1,5-AG levels correlated inversely with serum Cre levels especially in patients with Cre ≥2.0 mg/dl . Based on the reported relationship between 1,5-AG blood levels and HbA1c <8.0% and Cre <2.0 mg/dl described above [14, 15], we focused in this study on patients with HbA1c <8.0%.
Blood 1,5-AG level is a marker of glycemic control and accurately reflects rises and falls in urinary glucose excretion. When 1,5-AG leaks into the urine along with excessive excretion of glucose, the result is a decreased concentration in the blood. In other words, blood glucose levels correlate inversely with those of 1,5-AG . Because glucose is immediately excreted into the urine even after a very short period of postprandial hyperglycemia, 1,5-AG was previously reported to serve as a marker of glycemic control that reflects fluctuations in blood glucose [20–22]. On the other hand, in relation to complications, 1,5-AG reportedly correlates with albuminuria  and the cardio-ankle vascular index , independent of HbA1c. A cohort study that followed subjects for a mean of 11 years demonstrated 1,5-AG to be a strong predictor of CVD . Emoto et al.  reported that improvement in flow mediated dilation during a period of α-glucosidase administration was associated with 1,5-AG improvement in patients with type 2 diabetes accompanied by coronary artery disease. However, there is only limited information on 1,5-AG and vascular endothelial function, and no study free of the effects of drug treatments has yet been reported. In the present study, vascular endothelial function, evaluated by PAT, correlated strongly with 1,5-AG, suggesting the 1,5-AG level is a potentially useful predictor of vascular endothelial function, as well as a marker of fluctuations in blood glucose, in patients with HbA1c <8%. Based on this result, we believe that 1,5-AG should be evaluated in patients with HbA1c <8%, and that treatment of postprandial hyperglycemia and multidisciplinary risk management for atherosclerosis should be provided to patients with low 1,5-AG levels.
L_RHI is mainly an index of vascular endothelial function that reflects vasodilatory responses to NO, an endothelium-dependent vasodilatory factor . Vascular endothelial function determined by L_RHI is reported to allow detection of atherosclerosis at an early stage and to correlate with coronary atherosclerosis , as well as to predict coronary artery disease . As for the relationship between glucose metabolism and vascular endothelial function, it is known that increased oxidative stress and fluctuations in blood glucose together worsen vascular endothelial dysfunction , and indices of fluctuations in blood glucose, such as MAGE and postprandial hyperglycemia, correlate strongly with vascular endothelial function . Specifically, fluctuations in blood glucose and postprandial hyperglycemia are considered to be major factors favoring the progression of vascular endothelial dysfunction in glucose metabolism. On the other hand, it was recently reported that 1,5-AG correlates with MAGE and postprandial hyperglycemia in CGM [16, 27]. The findings of this study indicate that 1,5-AG correlates strongly with vascular endothelial function because it is a marker of glycemic control that reflects, particularly fluctuations in blood glucose and postprandial hyperglycemia.
This study has several limitations. First, this study did not include control subjects free of diabetes mellitus. Second, we did not evaluate the relationship between vascular endothelial function with either oxidative stress or inflammation. Third, about half of the subjects were on treatment intended to improve lipid metabolism. Although a relationship between L_RHI and blood pressure or the ratio of TC to HDL-C was found in a large-scale cohort study , no relationship was found between L_RHI and blood pressure or lipid metabolism in our study, presumably because most of our patients were on antihypertensive drugs or statins. Fourth, the determination coefficient of the independent variable was low for the model employed in this study, with the adjusted R2 being equal to 0.277 in multivariate analysis. The sample size was relatively small, and therefore the obtained results require further confirmation in a larger number of patients.