OBJECTIVE -To investigate fructose metabolic changes in patients with diabetes.RESEARCH DESIGN AND METHODS -Serum and urinary fructose concentrations were determined in healthy subjects (n ϭ 23) and in nondiabetic (n ϭ 23) and diabetic patients (n ϭ 26). Fructose was measured using our newly developed method, and 13 C 6 -fructose was used as the internal standard. After adding sample to a fixed amount of internal standard, ion-exchange resins and high-performance liquid chromatography pretreatments were performed. Then, the amount of fructose in the sample was measured by gas chromatography-mass spectrometry.RESULTS -Serum fructose concentrations in patients with diabetes (12.0 Ϯ 3.8 mol/l) were significantly higher than those in healthy subjects (8.1 Ϯ 1.0 mol/l, P Ͻ 0.001) and nondiabetic patients (7.7 Ϯ 1.6 mol/l, P Ͻ 0.001), and daily urinary fructose excretion was significantly greater in patients with diabetes (127.8 Ϯ 106.7 mol/day) than in nondiabetic patients (37.7 Ϯ 23.0 mol/day, P Ͻ 0.001). In patients with diabetes (n ϭ 20), serum fructose concentrations (8.6 Ϯ 1.8 mol/l, P Ͻ 0.001) and daily urinary fructose excretion (63.4 Ϯ 63.8 mol/day, P Ͻ 0.01) significantly decreased by week 2 after admission.CONCLUSIONS -The present results differed from those of previous studies in that we found that the serum and urinary fructose concentrations decreased rapidly, concomitant with an improvement in glycemia. Therefore, hyperglycemia was associated with increased serum and urinary fructose concentrations in patients with diabetes. Diabetes Care 25:353-357, 2002F ructose is an important dietary source of carbohydrates. In Western countries, daily intake of fructose by adults is ϳ100 g (1). Due to its unique metabolic properties, fructose promotes adverse metabolic changes, including glucose intolerance (2,3), hyperlipidemia (2,3), and hyperuricemia (4). Moreover, in light of nonenzymatic fructosylation of proteins (5), polyol pathway, and carbonyl stress, fructose is inferred to have an important role in the pathogenesis of diabetic complications. Therefore, if the measurement of serum fructose levels is clinically significant and available as a biomarker, it could be greatly useful. However, previous studies have reported no significant difference in serum fructose concentrations between diabetic and nondiabetic patients (6 -8). In these studies, the pretreatment of samples was insufficient to remove glucose, which interfered with the measurement of fructose. In this study, we report serum and urinary fructose concentrations measured by a newly developed method that overcomes this problem of glucose interference, and we describe fructose kinetic changes in patients with diabetes. RESEARCH DESIGN ANDMETHODS -Three subsets comprised the present study. First, serum fructose concentrations were determined in 23 healthy subjects and in 26 diabetic (diabetes group) and 23 nondiabetic (nondiabetic group) inpatients. Daily urinary fructose excretion was examined in the diabetes group and in the nondiabetic group. Ser...

The origin and disposal of 1,5-anhydro-D-glucitol (AG), one of the main polyols found in the human body, was studied in normal subjects and diabetic patients. AG was detected in various kinds of foods. The mean AG supplement through foods was estimated to be approximately 4.38 mg/day, which was compatible with that calculated in a food analysis (average 0.22 mg AG/100 kcal in Japanese foods) on eight healthy subjects. The mean AG excretion in urine was approximately 4.76 mg/day in these subjects. Excretion into stools was negligible. From observations on the patients without oral supplement of AG, 0.4 mg of daily de novo synthesis of AG was strongly suggested. It was also implied that urinary AG excretion occurred soon after food ingestion and that its amount was closely correlated with daily supplement through foods. Thus the fundamental kinetics of AG were recognized as follows: 1) AG in the body originates mainly from foods and is well absorbed in the intestine, 2) AG is little degraded and metabolized in the body, and 3) an equilibrium exists between oral supplement plus a small but steady amount of de novo synthesis and excretion in urine.

To elucidate the value of using plasma 1,5-anhydro-D-glucitol (AG) as a marker of glycemic control in diabetic patients, the relationship between the plasma concentration of AG and glucosuria was examined in 152 patients with non-insulin-dependent diabetes mellitus (NIDDM). After recovery from the deterioration of glycemic control in NIDDM patients had started, AG began to increase day by day. The recovery of plasma AG showed a constant linear increase curve when excellent glycemic control was attained. The ordinary daily recovery rate of plasma AG was estimated to be 0.3 microgram/ml, which was independent of body weight, sex, age, the difference in treatment, the duration of diabetes, or the level of plasma AG among NIDDM patients. This rate decreased according to the increase in urinary glucose. When we calculated the decrease rate of plasma AG (delta AG), assuming 0.3 microgram/day to be the maximum increase rate in a day, we found a high correlation between delta AG and urinary glucose at almost all AG levels except the normal range and observed that plasma AG (A) times urinary glucose (G) was relatively constant. The formula A x G = 16 is a simple equation for rough estimation of urinary glucose from the plasma AG concentration in a stable glycemic-controlled NIDDM patient, and we call it the A.G index. The plasma AG also correlated significantly with fasting plasma glucose (r = -.810) and glycosylated hemoglobin (r = -.856) in the same stable glycemic-controlled NIDDM patients. Based on these observations, we propose that plasma AG can serve as a new marker that may provide sensitive and analytical information about glycemic control.

Summary.The urinary excretion of 1,5-anhydro-D-glucitol, a pyranoid polyol, in humans was studied. The plasma of nondiabetic human subjects contained high concentrations of this polyol (> 110 ~tmol/1), and there was a tendency for the 24-h excretion of it to become more variable in direct proportion to its plasma concentration. In contrast, diabetic patients showed lower plasma concentrations of this polyol, and the variation in the 24-h excretion of 1,5-anhydro-D-glucitol was especially notable among the patients with an extremely low plasma concentration of the polyol. This diabetic group showed a statistically significant correlation (p<0.01), between the urinary 1,5-anhydro-D-glucitol and urinary glucose. This correlation was more markedly demonstrated during a 100-g oral glucose tolerance test: parallel changes were observed in the concentrations of 1,5-anhydro-D-glucitol and glucose in the urine collected every hour after the glucose load. These observations led to the proposal that low plasma concentration of this polyol, which is observed in diabetes mellitus, may be the result of a frequent and/or prolonged high blood glucose concentration beyond the renal threshold for glucose excretion.Key words: 1,5-anhydroglucitol, urinary excretion, reabsorption, glucosuria, hyperglycaemia.A pyranoid polyol resembling glucose, 1,5-anhydro-Dglucitol (AG), is a humoral component in humans and other mammals [1][2][3][4][5][6][7][8][9][10][11][12]. The plasma AG concentration is specifically reduced in diabetes mellitus [10] and shows several dynamic properties which are advantageous as a clinical marker for diabetes mellitus. First, the extent of the plasma AG reduction is apparently correlated with the severity of diabetes mellitus, and strict metabolic control can reverse this reduction [11]. Second, AG undergoes very slow turnover in vivo [8,12], and its plasma concentration remains stable over a 24-h period, showing little acute response to fasting, food intake, and insulin administration [11]. Finally, AG also shows chemical and biochemical stability [12], and accordingly, we found no significant limitation on the storage and transport of plasma samples for AG determination. On the other hand, the utility of the plasma AG concentration as a clinical marker is certainly limited by a lack of metabolic knowledge: the origin and clearance mechanism of AG in humans have not yet been established. Recently, we demonstrated the primary role of renal AG reabsorption in AG retention in rats and mice [12]. That study also indicated a possibility that the diabetic plasma AG reduction is due to a decrease in renal AG reabsorption. In order to evaluate in humans the role of renal function in AG retention in the circulation, we measured the urinary AG and urinary glucose as well as the plasma AG and blood glucose. Subjects and methods SubjectsStudy 1. The amounts of AG and glucose in the blood and in a 24-h urine sample were determined for 11 non-diabetic volunteers and 30 diabetic patients, which included two patients with Typ...