Maternal Serum Polyols and Its Link to Gestational Diabetes Mellitus: A Population-Based Nested Case-Control Study.

CONTEXT: Sugar alcohols (also called polyols) are regarded as a "healthy" sugar substitute. One of the possible reasons for their safe use in pregnant women is their natural origin and the presence of polyols in maternal and fetal samples during normal human gestation. But little is known about the association between circulating sugar alcohols levels and maternal metabolic disorders during pregnancy. OBJECTIVE: We aimed to detect the concentration of the polyols in participants with and without gestational diabetes mellitus (GDM), and to investigate the association between maternal serum levels of polyols and GDM, as well as newborn outcomes. METHODS: A nested population-based case-control study was conducted in 109 women with and without GDM. Maternal concentrations of serum erythritol, sorbitol, and xylitol in the fasting state were quantified using a time of flight mass spectrometry system. RESULT: In women with GDM, serum concentrations of erythritol and sorbitol were higher, but serum concentrations of xylitol were lower than those in women without GDM. Per 1-SD increment of Box-Cox-transformed concentrations of erythritol and sorbitol were associated with the increased odds of GDM by 43% and 155% (95% CI 1.07-1.92 and 95% CI 1.77-3.69), while decreased odds were found for xylitol by 25% (95% CI 0.57-1.00). Additionally, per 1-SD increase of Box-Cox-transformed concentrations of serum sorbitol was associated with a 52% increased odds of large for gestational age newborns controlling for possible confounders (95% CI 1.00-2.30). CONCLUSION: Maternal circulating sugar alcohols levels during pregnancy were significantly associated with GDM. These findings provide the potential roles of polyols on maternal metabolic health during pregnancy.

Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis.

BACKGROUND: Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. RESULTS: We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank test). CONCLUSION: Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis.

Effect of glucagon on the xylitol-induced increase in the plasma concentration and urinary excretion of purine bases.

To investigate whether glucagon affects the xylitol-induced increase in the production of purine bases (hypoxanthine, xanthine, and uric acid), the present study was performed with five healthy subjects. Intravenous administration of 300 mL 10% xylitol increased the plasma concentration and urinary excretion of purine bases, erythrocyte concentrations of adenosine monophosphate (AMP) and adenosine diphosphate (ADP), and blood concentrations of glyceraldehyde-3-phosphate (GA3P) + dihydroxyacetone phosphate (DHAP), fructose-1,6-bisphosphate (FBP), and lactic acid; it decreased the blood concentration of pyruvic acid and the plasma concentration and urinary excretion of inorganic phosphate. However, intravenous administration of 1 mg glucagon together with xylitol reduced the xylitol-induced changes in oxypurines, pyruvic acid, GABP + DHAP, and FBP, whereas it promoted the xylitol-induced increase in the urinary excretion of total purine bases and did not affect the xylitol-induced increase in the plasma concentration of total purine bases. In addition, in vitro study demonstrated that sodium pyruvate prevented the xylitol-induced degradation of adenine nucleotides in erythrocytes. These results suggested that gluconeogenesis due to glucagon increased the production of pyruvic acid, accelerated the conversion of NADH to NAD, and thereby prevented both the xylitol-induced degradation of adenine nucleotides in organs similar to erythrocytes and the inhibition of xanthine dehydrogenase in the liver and small intestine, resulting in decreases in the plasma concentration and urinary excretion of oxypurines. However, it was also suggested that in the liver storing glycogen, glucagon-induced glycogenolysis accumulated sugar phosphates, resulting in purine degradation, since the xylitol-induced increase in the NADH/NAD ratio partially blocked glycolysis at the level of GABP dehydrogenase. Therefore, administration of glucagon together with xylitol may synergistically increase purine degradation more than xylitol alone, despite decreases in the plasma concentration and urinary excretion of oxypurines.

Xylitol-induced increase in the plasma concentration and urinary excretion of uridine and purine bases.

To determine whether xylitol increases the plasma concentration and urinary excretion of uridine together with purine bases, we administered xylitol (0.6 g/kg weight) intravenously to six normal subjects using a 10% xylitol solution. Xylitol infusion increased the plasma concentration and urinary excretion of uridine, as well as purine bases, while it decreased both the concentrations of inorganic phosphate in plasma and pyruvic acid in blood and increased the blood concentration of lactic acid. These results suggest that an increase in the plasma concentration and urinary excretion of uridine is ascribable to increased pyrimidine degradation following purine degradation induced by xylitol.

Effects of fructose and xylitol on the urinary excretion of adenosine, uridine, and purine bases.

To examine whether fructose and xylitol increase the plasma concentration and urinary excretion of adenosine, as well as uridine and purine bases (hypoxanthine, xanthine, and uric acid), we intravenously administered xylitol and, 2 weeks later, fructose, to five healthy subjects. Analyses of blood and urine samples obtained during these infusion studies demonstrated that fructose increased the urinary excretion of adenosine and uridine 11.9- and 105.5-fold, respectively, and caused only a small increase in the plasma concentrations of uridine and purine bases. It was further demonstrated that xylitol increased the urinary excretion of uridine 58.4-fold, with a marked increase in the plasma concentrations of purine bases and uridine but without an increase in the urinary excretion of adenosine. However, neither infusion increased the plasma concentration of adenosine. These results suggest that in addition to many organs, including the liver, fructose is significantly metabolized by an abrupt adenosine triphosphate (ATP) consumption in the kidney, leading to an increase in the urinary excretion of adenosine and uridine. They also suggest that xylitol is not significantly metabolized in the kidney.

Xylitol mediated amelioration of acetylphenylhydrazine-induced hemolysis in rabbits.

Xylitol was investigated for its ability to ameliorate hemolytic anemia induced by acetylphenylhydrazine in rabbits. Animal experiments were performed using two different concentrations of xylitol, a 5% and a 10% solution with a total dose of 2 g/kg body weight and infusion rates of 10 mg and 20 mg xylitol per kg body weight per minute respectively. Two doses of acetylphenylhydrazine (APH), 5 and 10 mg per kg, were injected intraperitoneally as hemolytic inducers in different groups of rabbits. All the rabbits infused with xylitol showed significantly less acute APH-induced hemolysis. The isotonic 5% xylitol solution was found to maintain and restore the hematological parameters (packed cell volume, hemoglobin concentration, reduced glutathione (GSH) content, and reticulocyte counts) better than the 10% xylitol solution. Increased 51CR-red cell survival confirmed the beneficial effect of xylitol. The survival of erythrocytes as represented by chromium-labeling in rabbits infused with 5% xylitol after treatment with 10 mg/kg APH increased from about 33% (the survival of red cells in rabbits injected with APH alone) to 67% of normal rabbits' red cell survival. Erythrocytes in APH-treated animals took up xylitol more readily than erythrocytes from control animals. Our results in rabbits suggest that (1) non-toxic dosage of xylitol is effective in ameliorating the hemolytic episode induced by APH, (2) there is a dose relationship between the hemolytic effect induced by APH and the preventive effect offered by xylitol, (3) drug-challenged cells effectively acquired two to three fold more xylitol to compensate for the cellular needs than that of the normal cells, and (4) sufficient xylitol (55 mg/dl) to act as substrate for xylitol dehydrogenase was recovered intracellularly in drug-challenged rabbit erythrocyte in vivo, in spite of a low plasma (less than 30 mg/dl) concentration of the substrate. This antihemolytic affect of xylitol is likely accomplished through NADPH generation, which maintains the level of GSH and protects the hemoglobin and other structural and functional proteins against peroxidative damage.

The comparative oxidation of glucose, fructose, sorbitol and xylitol in normal man.

The aim of the study was to compare the effects of fructose, sorbitol and xylitol with those of glucose on blood glucose and insulin levels and carbohydrate utilization in man. The experiment was performed by means of continuous indirect calorimetry in five groups of five to six normal volunteers during infusion of either glucose, fructose, sorbitol, xylitol or a mixture of fructose, glucose and xylitol in the proportion of 2:1:1. Glucose and insulin did not present any important variations during the fructose, sorbitol and xylitol infusiosns. However, carbohydrate oxidation rose significantly during administration of these substrates. Carbohydrate oxidation rose 80 mg/min for fructose, 27 mg/min for sorbitol, 39 mg/min for xylitol and 75 mg/min for the carbohydrate mixture, in comparison to 101 mg/min for glucose. It is concluded that fructose, sorbitol and xylitol provoke an increase in carbohydrate utilization without a corresponding rise in glycemia and insulinemia.

Effects of xylitol on urea synthesis in normal humans: relation to glucagon.

BACKGROUND: Xylitol exerts a nitrogen-sparing effect in stress catabolic states with hyperglucagonemia, but the mechanism(s) is unknown. We examined the effects of xylitol on urea synthesis during physiologic glucagon concentrations and during hyperglucagonemia. METHODS: Urea synthesis was measured independently of blood amino acid concentration by means of functional hepatic nitrogen clearance (FHNC) (ie, the linear slope of the relation between urea synthesis rate and blood alpha-amino nitrogen concentration during infusion of alanine). FHNC was measured on four separate occasions in each of seven healthy subjects: during constant infusion of alanine alone, alanine superimposed on a constant infusion of xylitol (blood xylitol 1 mmol/L), alanine superimposed on infusion of glucagon, and alanine superimposed on infusions of xylitol and glucagon. RESULTS: During alanine infusion alone, plasma glucagon rose to -170 ng/L, and FHNC was (mean +/- sem) 27.9 +/- 1.3 L/h. Xylitol did not affect plasma glucagon and only moderately reduced FHNC to 24.3 +/- 1.0 L/h (p < .05). Glucagon infusion increased plasma glucagon to -450 ng/L and FHNC twofold to 50.9 +/- 6.2 L/h; this increase was totally prevented by the addition of xylitol that reduced FHNC to 27.4 +/- 2.6 L/h (p < .01). CONCLUSIONS: The results show that xylitol only inhibited FHNC minimally during spontaneous glucagon levels. In contrast, xylitol completely inhibits the increase in FHNC by glucagon. This suggests that the mechanism whereby xylitol reduces nitrogen loss in stress catabolic conditions with hyperglucagonemia involves an effect on liver metabolism. The mechanism is unknown but may be related to depletion of hepatocyte adenine nucleotides.

Effects of xylitol on urea synthesis in patients with cirrhosis of the liver.

BACKGROUND: In individuals with cirrhosis the normal inhibiting effect of glucose on urea synthesis is lost, probably because of very high concentrations of glucagon. In agreement, glucose does not prevent the inducing effect of glucagon on urea synthesis in normal humans. In contrast, the sugar alcohol, xylitol, prevents the increasing effect of glucagon in normal humans. We, therefore, examined the effect of xylitol on urea synthesis in individuals with cirrhosis and hyperglucagonemia. METHODS: Urea synthesis, calculated as urinary excretion rate corrected for accumulation in total body water and intestinal loss, was measured during infusion of alanine (2 mmol/[h x kg body wt]) and during infusion of alanine superimposed on infusion of xylitol (0.12 g/[h x kg body wt]) in 8 individuals with biopsy-proven alcoholic cirrhosis. The functional hepatic nitrogen clearance (FHNC), ie, urea synthesis expressed independent of changes in plasma amino acid concentration, was calculated as the slope of the linear relation between the urea synthesis rate and the plasma amino acid concentration. RESULTS: All individuals had elevated basal plasma glucagon concentration (261 +/- 61 ng/L; mean +/- SEM) and a markedly increased response to alanine infusion (1037 +/- 226 ng/L). This was not changed by xylitol. Neither the basal urea synthesis rate (13.2 +/- 2.5 mmol/h) nor the alanine-stimulated urea synthesis rate (76.8 +/- 3.64 mmol/h) was changed by xylitol. FHNC during the infusion of alanine alone was 10.5 +/- 0.9 L/h and did not change during the concomitant infusion of xylitol (10.1 +/- 1.1 L/h). CONCLUSIONS: Xylitol reduces neither urea synthesis nor FHNC. The data do not support an important role of xylitol as a nitrogen-sparing agent in cirrhosis.

Novel perfluoroalkylated derivatives of D-galactopyranose and xylitol for biomedical uses. Hemocompatibility and effect on perfluorocarbon emulsions.

6-O-(4,4,5,5,6,6,7,7,7-Nonafluoro-2-hydroxyheptyl)-, 6-O-(4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluoro-2-hydroxynonyl)-, and 6-O-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoro-2-hydroxyundecyl)-d-galactopyranose (9, 10, and 11, resp.) were prepared by a two-step synthesis including the reaction of 1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranose with 2-[(perfluoroalkyl)methyl]oxiranes under catalysis with BF(3).Et(2)O. Similarly, 1-O-(4,4,5,5,6,6,7,7,7-nonafluoro-2-hydroxyheptyl)-, 1-O-(4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluoro-2-hydroxynonyl)-, 1-O-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoro-2-hydroxyundecyl)-dl-xylitol (18, 19, and 20, resp.) were prepared by a two-step synthesis from the corresponding 1,2:3,4-di-O-isopropylidene-dl-xylitol. Most of the both types of fluoroalkylated carbohydrate derivatives 9-11 and 18-20 generally displayed very low level of hemolytic activity and excellent co-emulsifying properties on testing on perfluorodecalin-Pluronic F-68 microemulsions.

Xylitol-induced increase in the concentration of oxypurines and its mechanism.

We investigated the effect of xylitol on the plasma concentration and the urinary excretion of purine bases, 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid in subjects who had ingested pyrazinamide (60 mg/kg weight). One liter of 10% xylitol was infused intravenously over 2 hours to 5 subjects to whom pyrazinamide had been administered 10 hours before. Xylitol increased the plasma concentration of uric acid, hypoxanthine and xanthine, the urinary excretion of hypoxanthine and a ratio of lactic acid/pyruvic acid in blood, while it decreased the plasma concentration and the urinary excretion of inorganic phosphate, 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid. These results suggested that in addition to an increase in purine degradation by xylitol, xylitol-induced increase in the cytosolic NADH inhibited xanthine dehydrogenase activity in the liver and the small intestine.

The intravenous xylitol tolerance test in non-lactating cattle.

Xylitol is a five-carbon sugar alcohol that is often used for treatment of ketosis in dairy cattle in Japan. An intravenous xylitol tolerance test (IVXTT, 0.1 g/kg, bolus injection through the jugular vein) was performed in 4 non-lactating cows (n = 4) and the results were compared with those of an intravenous glucose tolerance test (IVGTT) performed under equivalent conditions. The serum xylitol concentration reached a peak value (41.4+/-9.0 mg/dl) at 5 min, and then rapidly decreased and almost disappeared within 2 h. The C0 for xylitol was 56.9+/-16.6 mg/dl and the t(1/2) was 8.5+/-0.9 min. The administration of xylitol appeared to cause similar secretion of insulin to that caused by glucose. There was also a reduction in the concentration of free fatty acids. It seems that xylitol has value for the treatment of ketosis. However, rapid administration of xylitol appeared to have an osmotic diuretic action and might be a cause of dehydration.

Assessment of xylitol serum levels during the course of parenteral nutrition including xylitol in intensive care patients: a case control study.

BACKGROUND & AIMS: Xylitol has been approved for parenteral nutrition and may be beneficial in catabolic situations. The aim was to establish an easy method to monitor xylitol serum levels in patients receiving xylitol and to determine whether xylitol is safe. METHODS: A commercially available xylitol test was validated and used to measure serum levels in 55 patients admitted to our intensive care unit with an indication for parenteral nutrition with xylitol for at least 24 h. Controls consisted of the most recent 56 patients admitted to the intensive care unit who received parenteral nutrition without xylitol for at least 2 days. Xylitol serum levels were determined using the test. Adverse events, liver enzymes, lactate, bilirubin, γ-glutamyl transpeptidase, and insulin requirement were secondary endpoints. RESULTS: Patients receiving xylitol received 32.6% less insulin than controls. The amount of energy they received was comparable (xylitol: 810.1; controls: 789.8 kcal). Mean liver enzymes and lactate levels were similar in both groups. Adverse events considered attributable to xylitol did not occur. Xylitol did not accumulate in patients' blood and returned to near baseline values one day after parenteral nutrition was stopped. CONCLUSIONS: Parenteral nutrition with xylitol appears to be safe for critical care patients. There were no signs of hepatoxicity. TRIAL REGISTRATION DRKS: DRKS00004238.