The urinary Isoxanthopterin/pterin Ratio Reflects Mild Fasting Hyperglycemia in Obese Patients with Type 2 Diabetes Mellitus: An Exploratory Cross-sectional Study.

Objective The exaggerated activation of xanthine oxidase (XO) provokes oxidative stress, a feature of type 2 diabetes mellitus (T2DM) and obesity. Because measuring the plasma XO activity is complicated, we tested whether urinary isoxanthopterin (IXP), the end product of pterin metabolism catalyzed by XO, could serve as an alternative marker. Methods We enrolled 51 patients with mild T2DM and obesity (BMI ≥25 kg/m2; median HbA1c 6.7%) and 9 healthy individuals. Urinary IXP level was determined by HPLC-FL. Correlations between 24-hour and spot urinary IXP were examined in healthy individuals to validate spot urine, followed by analyses in patients stratified by the median IXP/Pterin ratio. Results In healthy individuals, spot urinary IXP correlated with 24-h measurements (r=0.795, p=0.010); however, both urinary IXP levels and the IXP/Pterin ratio were not correlated with the XO activity. In patients with mild T2DM and obesity, the urinary IXP/pterin ratio was significantly associated with fasting plasma glucose (p=0.030). Among patients with higher urinary IXP/Pterin ratios, this association was tightly independent of other clinical parameters (p=0.028). Conclusion The level of spot urinary IXP was correlated with that of 24-h excretion, but not with circulating XO activity. The ratio of IXP/Pterin was associated with fasting hyperglycemia and provides a novel avenue to evaluate glucose dysmetabolism in obese patients with mild T2DM.