The Abnormally High Level of Uric D-Ribose for Type-2 Diabetics

In 1815, the French chemist Michel Eugene Chevreul (1786-1889) discovered that the sweetness in the urine of diabetics comes from grape sugar or D-glucose. Diabetes mellitus (DM) is considered as a group of metabolic diseases characterized by hyperglycemia (high concentration of blood D-glucose) resulting from defects in insulin secretion, insulin action, or both. On the other hand, D-ribose as an energetic enhancer was found to decrease the concentration of blood D-glucose, and thus "Oral administration of D-ribose in diabetes mellitus" was ever described by Steinberg and colleagues (1970). As described previously in this laboratory, D-ribose rapidly glycates proteins, such as BSA, neuronal Tau and alpha-synuclein, producing advanced glycation end products (AGEs) with severe cytotoxicity, leading to dysfunction and cell death, in vitro and in vivo. Intraperitoneal injection of D-ribose into mice significantly increases their glycated serum protein and blood AGEs though the concentration of D-glucose became slightly decreased, suggesting that D-ribose is much easier to produce AGEs than D-glucose in vivo. Here, using 4-(3-Methyl-5-oxo-2-pyrazolin-1-yl) benzoic acid (MOPBA) coupled with HPLC, we determined the concentration of uric D-ribose of type 2 diabetic patients (n=30) and the age-matched healthy controls (n=30). The results show that the yield of the derivative of MOPBA-ribose is linearly correlated with the concentration of D-ribose (r(2)=0.999) with a recovery of 99%. The isolated fractions of D-ribose and D-glucose from urine of type 2 diabetic patients through HPLC were analyzed by mass spectrometry, and the results showed that the fractions contained 569.19 u compound (C27H29N4O10, D-ribose), and 599.20 u compound (C28H31N4O11, D-glucose) respectively. The concentration of uric D-ribose of Type 2 diabetics (male (134.28 +/- 35.09) mu mol/L, female (97.33 +/- 23.68) mu mol/L) was significantly (P < 0.001) higher than that of the age-matched healthy control (male (35.99 +/- 5.64) mu mol/L, female (33.72 +/- 6.27) mu mol/L). Under the experimental conditions, the uric D-glucose level of the patients was also markedly (P < 0.001) higher than the control. Further analyses showed a marked increase in the level of uric D-ribose from either male (P < 0.001) or female (P < 0.001), but a significant difference of the uric levels between male and female could not be observed (P> 0.05). The high levels of uric D-ribose and D-glucose of the patients suggest that type 2 diabetic patients are not only suffered from D-glucose metabolism disorders, but also from D-ribose metabolism disorders.