J.L.D. Wattimena

Immediate commencement of amino acid supplementation in preterm infants: Effect on serum amino acid concentrations and protein kinetics on the first day of life

To determine whether the general reluctance to begin amino acid administration to preterm infants from birth onward might lead to loss of lean body mass and impairment of growth, we measured amino acid levels and protein kinetics in 18 preterm infants. Nine infants received amino acids (1.15 +/- 0.06 gm.kg-1.day-1) and glucose (6.05 +/- 1.58 gm.kg-1.day-1), whereas the other nine infants received only glucose (6.48 +/- 1.30 gm.kg-1.day-1) from birth onward. Protein kinetics on the first postnatal day were measured with a stable isotope dilution technique with [1-13C]leucine as a tracer. No statistically significant differences were noted in blood pH, base excess, urea concentration, or glucose levels. Both total amino acid concentration and total essential amino acid concentration were significantly lower and were below the reference range in the nonsupplemented group. Plasma amino acid levels of five essential amino acids (methionine, cystine, isoleucine, leucine, arginine) were below the reference range in the nonsupplemented group, whereas only cystine was below the reference range in the supplemented group. Nitrogen retention was improved significantly by the administration of amino acids (-110 +/- 44 mg nitrogen per kilogram per day in the glucose-only group vs +10 +/- 127 mg nitrogen per kilogram per day in the group given glucose and amino acids; p = 0.001); leucine oxidation was not significantly increased in the supplemented group (41 +/- 13 mumol.kg-1.hr-1 vs 46 +/- 16 mumol.kg-1.hr-1). Leucine balance also improved significantly (-41 +/- 13 mumol.kg-1.hr-1 vs -8 +/- 16 mumol.kg-1.hr-1; p = 0.01) because of a combination of an increased amount of leucine being used for protein synthesis and a lower amount of leucine coming from protein breakdown. Plasma cystine concentration, the only amino acid below the reference range in the supplemented group, was highly predictive for protein synthesis in that group. We conclude that the administration of amino acids to preterm infants from birth onward seems safe and prevents the loss of protein mass.

Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis.

Protein-energy malnutrition as a result of anorexia frequently occurs in dialysis patients. In patients who are on peritoneal dialysis (PD), dialysate that contains amino acids (AA) improves protein anabolism when combined with a sufficient oral intake of calories. It was investigated whether protein anabolism can be obtained with a mixture of AA plus glucose (G) as a source of proteins and calories during nocturnal automated PD (APD). A random-order cross-over study was performed in eight APD patients to compare in two periods of 7 d each AA plus G dialysate obtained by cycler-assisted mixing of one bag of 2.5 L of AA (Nutrineal 1.1%, 27 g of AA) and four bags of 2.5 L of G (Physioneal 1.36 to 3.86%) versus G as control dialysate. Whole-body protein turnover was determined using a primed continuous infusion of L-[1-13C]leucine, and 24-h nitrogen balance studies were performed. During AA plus G dialysis, when compared with control, rates of protein synthesis were 1.20 +/- 0.4 and 1.10 +/- 0.2 micromol/kg per min leucine (mean +/- SD), respectively (NS), and protein breakdown rates were 1.60 +/- 0.5 and 1.72 +/- 0.3 micromol/kg per min (NS). Net protein balance (protein synthesis minus protein breakdown) increased on AA plus G in all patients (mean 0.21 +/- 0.12 micromol leucine/kg per min; P < 0.001). The 24-h nitrogen balance changed by 0.96 +/- 1.21 g/d, from -0.60 +/- 2.38 to 0.35 +/- 3.25 g/d (P = 0.061, NS), improving in six patients. In conclusion, APD with AA plus G dialysate improves protein kinetics. This dialysis procedure may improve the nutritional status in malnourished PD patients.

Safety and efficacy of early parenteral lipid and high-dose amino acid administration to very low birth weight infants

OBJECTIVE To assess the efficacy and safety of early parenteral lipid and high-dose amino acid (AA) administration from birth onwards in very low birth weight (VLBW, birth weight <1500 g) infants. STUDY DESIGN VLBW infants (n = 144; birth weight 862 ± 218 g; gestational age 27.4 ± 2.2 weeks) were randomized to receive 2.4 g of AA kg(-1) · d(-1) (control group), or 2.4 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (AA + lipid group), or 3.6 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (high AA + lipid group) from birth onwards. The primary outcome was nitrogen balance. The secondary outcomes were biochemical variables, urea rate of appearance, growth rates, and clinical outcome. RESULTS The nitrogen balance on day 2 was significantly greater in both intervention groups compared with the control group. Greater amounts of AA administration did not further improve nitrogen balance compared with standard AA dose plus lipids and was associated with high plasma urea concentrations and high rates of urea appearance. No differences in other biochemical variables, growth, or clinical outcomes were observed. CONCLUSIONS In VLBW infants, the administration of parenteral AA combined with lipids from birth onwards improved conditions for anabolism and growth, as shown by improved nitrogen balance. Greater levels of AA administration did not further improve the nitrogen balance but led to increased AA oxidation. Early lipid initiation and high-dose AA were well tolerated.

Nocturnal oral glucose supplementation. The Effects on protein metabolism in cirrhotic patients and in healthy controls

Nocturnal glucose administration might prevent gluconeogenesis and concomitant protein loss due to hepatic glycogen depletion. In this study the effects of nocturnal oral glucose supplements on nitrogen metabolism were investigated in 8 cirrhotic patients and in 8 healthy controls. During the night, either polymeric glucose was given or water as placebo. In the patients with cirrhosis on placebo, nitrogen balance was not different from controls: -63 +/- 8 vs. -55 +/- 4 mg N/kg b.wt./9 h (mean +/- SEM). Cirrhotic patients had increased nocturnal protein turnover rates (measured with 15N-glycine) and increased early morning levels of free fatty acids (FFA), lactate, insulin, glucagon and growth hormone. After glucose, nitrogen balance improved by 36% in the cirrhotic group, with a decrease in protein turnover rates and a decrease in plasma levels of beta-hydroxybutyrate, urea and glucagon. In the controls, glucose had no effects on nitrogen balance, on protein turnover or on the hormone levels, except for reduced FFA and ketone body levels. These data show that nocturnal calorie supplements improve nitrogen balance during the night in cirrhotic patients but not in healthy controls. Long interprandial intervals should be avoided in cirrhotic patients.

Whole-body protein turnover in preterm appropriate for gestational age and small for gestational age infants: comparison of [15N]glycine and [1-(13)C]leucine administered simultaneously.

ABSTRACT: Measurements of whole-body protein turnover in preterm infants have been made using different stable isotope methods. Large variation in results has been found, which could be due to different clinical conditions and/or the use of different tracers. We studied 14 appropriate for gestational age and nine small for gestational age orally fed preterm infants using [15N]glycine and [1-13C]leucine simultaneously, which allowed us to make a comparison of commonly used methods to calculate whole-body protein turnover. Whole-body protein turnover was calculated from 15N enrichment in urinary ammonia and urea after [15N]-glycine administration and from the 13C enrichment in expired CO2 after administration of [1-13C]leucine. Enrichment of α-ketoisocaproic acid after [1-13C]leucine constant infusion was measured as a direct parameter of whole-body protein turnover. Group means for whole-body protein turnover using [15N]glycine or [1-13C]leucine ranged from 10 to 14 g.kg-1.d-1, except when using the end product method that assumes a correlation between leucine oxidation and total nitrogen excretion. We found very low 15N enrichment of urinary urea in the majority of small for gestational age infants. These infants also had a lower nitrogen excretion in urine and oxidized less leucine. Nitrogen balance was higher in small for gestational age infants (416 pm 25 mg±kg-1d-1) compared with appropriate for gestational age infants (374 pm 41 mg±kg-1d-1, p= 0.003). [15N]Glycine does not seem to exchange its label with the body nitrogen pool to a significant degree and is therefore not always suitable as a carrier for 15N in protein turnover studies in premature infants.

Peritoneal Dialysis with Solutions Containing Amino Acids Plus Glucose Promotes Protein Synthesis during Oral Feeding

Inadequate food intake plays an important role in the development of malnutrition. Recently, an increased rate of protein anabolism was shown in fasting state in patients who were on automated peritoneal dialysis with combined amino acids (AA) and glucose (G) dialysate serving as a source of both proteins and calories. This study investigated the effects of such a dialysis procedure in the daytime in the fed state in patients who were on continuous ambulatory peritoneal dialysis (CAPD). A crossover study was performed in 12 CAPD patients to compare, at 7-d intervals, a mixture of AA (Nutrineal 1.1%) plus G (Physioneal l.36 to 3.86%) versus G only as control dialysate. Whole-body protein turnover was studied by primed constant intravenous infusion of (13)C-leucine during the 9-h dialysis. For meeting steady-state conditions during whole-body protein turnover, frequent exchanges with a mixture of AA plus G were done using an automated cycler. Fed-state conditions were created by identical liquid hourly meals. Using AA plus G dialysate, as compared with the control, rates of protein synthesis increased significantly (2.02 +/- 0.08 versus 1.94 +/- 0.07 mumol leucine/kg per min [mean +/- SEM]; P = 0.039). Rates of protein breakdown and net protein balance did not differ significantly between AA plus G and G. In conclusion, dialysate that contains AA plus G also improves protein synthesis in fed CAPD patients. The use of such a mixture may contribute to long-term improvement of the nutritional status in malnourished CAPD patients with deficient food intake.

Evaluation Studies of the 13C-Mixed Triglyceride Breath Test in Healthy Controls and Adult Cystic Fibrosis Patients with Exocrine Pancreatic Insufficiency

The 13C-mixed triglyceride (13C-MTG) breath test (BT) is a safe and noninvasive method to measure exocrine pancreatic function. We examined the reproducibility of the 13C-MTG BT in a group of 17 healthy controls and 8 adult patients with cystic fibrosis (CF). In controls no statistically significant difference in percentage dose recovered (PDR) was found between the first and the second result of repeated tests: the mean values were 35.5 +/- 5.5 vs. 32.3 +/- 7.4 PDR (n = 17). Also in the group of CF patients (n = 8) no significant difference between duplicate tests was found: mean values 17.5 +/- 7.5 and 17.5 +/- 7.8 PDR, respectively. The coefficient of repeatability is 8 PDR for the controls and CF patients together. Two factors might influence the outcome of the test. First, individually measured CO2 excretion instead of the usually assumed 9 mmol/h/kg CO2 production might alter the result of the 13CO2-MTG BT. Therefore CO2 production was measured by indirect calorimetry in 12 healthy controls and 13 CF patients. Measured CO2 excretion was not significantly different between healthy controls and CF patients. Secondly, exercise might influence BT results due to its separate effects on both CO2 production and excretion. The influence of physical exercise at a level of 25 or 50 W was studied on a bicycle ergometer in 4 healthy controls during the last 5 min of each 30-min sampling period. Exercise gave lower test results, on average 85% of the PDR value at rest. Incidently, it was observed in 1 patient that use of 13C-enriched food during the day preceding the test caused inappropriately low test results in the 13C-MTG BT. The 13C-MTG BT is a test with a fair but less than desirable reproducibility. Test conditions should be standardized to eliminate confounding influences. Exercise should be limited or strictly defined. Diet on the day preceding the test should not contain naturally 13C-enriched food. There is no need to measure individual CO2 production.

Splanchnic oxidation is the major metabolic fate of dietary glutamate in enterally fed preterm infants

The intestine is a major site of amino acid metabolism, especially in neonates. The energy needed for the metabolic processes in neonatal animals is derived from dietary glucose and amino acids. No data are available showing that dietary amino acids function as intestinal fuel source in human neonates as well. We hypothesized that preterm infants show a high splanchnic first-pass glutamate metabolism and the primary metabolic fate of glutamate is oxidation. Five preterm infants (birth weight 1.2 ± 0.2 kg, gestational age 29 ± 1 wk) were studied by dual tracer ([U-13C]glutamate and [D3]glutamate) techniques on two study days (within postnatal d 14–19). Splanchnic and whole-body glutamate kinetics were assessed by plasma isotopic enrichment of [U-13C]glutamate and [D3]glutamate and breath 13CO2 enrichment. Fractional first-pass glutamate uptake was 77 ± 18% on d 1, and 70 ± 7% on d 2, mean 74 ± 13%. Almost all (86 ± 7%) of the glutamate used in the first pass is directed toward oxidation. There is a high splanchnic fractional first-pass uptake and a high oxidation rate of glutamate in preterm infants. Glutamate is an important source of energy for the splanchnic tissues in preterm infants receiving full enteral feeding.

Peritoneal protein losses and cytokine generation in automated peritoneal dialysis with combined amino acids and glucose solutions.

Objectives. Protein-energy malnutrition as a consequence of deficient protein intake frequently occurs in peritoneal dialysis (PD) patients. Previously, we showed that peritoneal dialysate containing a mixture of amino acids (AA) and glucose has anabolic effects. However AA-dialysate has been reported to increase intraperitoneal protein and AA losses and the release of proinflammatory cytokines (interleukine-6 (IL-6) and tumor necrosis factor alpha (TNFα)). We investigated the effect of AA plus glucose (AAG) solutions on peritoneal protein losses and cytokine generation. Methods. In 6 patients on standard automated peritoneal dialysis (APD) 12 APD sessions of 6 cycles each were performed during the night using dialysate containing 1.1% AA plus glucose or glucose alone as control. Protein losses and TNFα and IL-6 concentrations were measured in dialysates separately collected from nightly cycling and daytime dwell. Results. The 24 hour-protein losses with AAG (median 6.7 g, range 4.7–9.4 g) were similar to control dialysate (median 6.0 g, range 4.2–9.2 g). Daytime dialysate IL-6 levels were higher after nightly AAG dialysis than after control dialysis (142 pg/ml and 82 pg/ml, respectively, P<.05). TNFα concentrations were very low. Conclusion. Nightly APD with amino acids containing dialysate was associated with an increase in peritoneal IL-6 generation during the day. The addition of AA to standard glucose dialysis solutions did not induce a significant increase of peritoneal protein losses.

Bioactive rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients

BACKGROUND Inadequate food intake plays an important role in the development of malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients. Aim of the study. The aim of the study was to investigate in CAPD patients whether circulating insulin-like growth factor-I (IGF-I) bioactivity may offer a more sensitive index to acute nutritional interventions than total IGF-I. METHODS An open-label, randomized, crossover study of 2 days-with a 1-week interval-was performed in 12 CAPD patients in the fed state to compare a mixture of amino acids (Nutrineal 1.1%) plus glucose (AA plus G) (Physioneal 1.36% to 3.86%) dialysate versus G only as control dialysate. Fed-state conditions were created by identical liquid hourly meals. IGF-I bioactivity was measured by the kinase receptor activation assay (IGF-I KIRA); total IGF-I was measured by immunoassay. RESULTS In the fed state, both after AA plus G as well as after G dialysis IGF-I bioactivity increased compared to baseline, while no changes in circulating total IGF-I levels were observed in both treatment arms. However, the increase in IGF-I bioactivity was only significant after AA plus G dialysis (P = 0.02). CONCLUSIONS Our results provide evidence that in CAPD patients changes in circulating IGF-I bioactivity are associated with nutrient intake and that IGF-I bioactivity rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients.