The gut takes nearly all: threonine kinetics in infants

BACKGROUND: Threonine is an essential amino acid that is abundantly present in intestinally produced glycoproteins. Animal studies show that intestinal first-pass threonine metabolism is high, particularly during a restricted enteral protein intake. OBJECTIVE: The objective of the study was to quantify intestinal first-pass threonine metabolism in preterm infants during full enteral feeding and during restricted enteral intake. DESIGN: Eight preterm infants (x +/- SD birth weight: 1.1 +/- 0.1 kg; gestational age: 29 +/- 2 wk) were studied during 2 periods. During period A, 40% of total intake was administered enterally and 60% was administered parenterally. Total threonine intake was 58 +/- 6 micromol kg(-1) h(-1). During period B, the infants received full enteral feeding, and the total threonine intake was 63 +/- 6 micromol kg(-1) h(-1). Dual stable-isotope tracer techniques were used to assess splanchnic and whole-body threonine kinetics. RESULTS: The fractional first-pass threonine uptake by the intestine was remarkably high in both periods: 82 +/- 6% during partial enteral feeding and 70 +/- 6% during full enteral feeding. Net threonine retention was not affected by the route of feeding. CONCLUSION: In preterm infants, the splanchnic tissues extract a very large amount of the dietary threonine intake, which indicates a high obligatory visceral need for threonine, presumably for the purposes of synthesis.     

Leucine metabolism in preterm infants receiving parenteral nutrition with medium-chain compared with long-chain triacylglycerol emulsions

BACKGROUND: Although medium-chain triacylglycerols (MCTs) may be utilized more efficiently than long-chain triacylglycerols (LCTs), their effect on protein metabolism remains controversial. OBJECTIVE: The aim of the study was to compare the effects of mixed MCT-LCT and pure LCT emulsions on leucine metabolism in preterm infants. DESIGN: Fourteen preterm [gestational age: 30+/-1 wk; birth weight: 1409+/-78 g (x +/- SE)] neonates were randomly assigned to receive, from the first day of life, either a 50:50 MCT-LCT (mixed MCT group; n = 7) or an LCT (LCT group; n = 7) lipid emulsion as part of an isonitrogenous, isoenergetic total parenteral nutrition program. On the fourth day, infants received intravenous feeding providing 3 g lipid, 15 g glucose, and 3 g amino acids kg(-1) x d(-1) and underwent 1) indirect calorimetry and 2) a primed, 2-h infusion of H13CO3Na to assess the recovery of 13C in breath, immediately followed by 3) a 3-h infusion of L-[1-13C]leucine. RESULTS: The respiratory quotient tended to be slightly but not significantly higher in the mixed MCT than in the LCT group (0.96+/-0.06 compared with 0.93+/-0.03). We did not detect a significant difference between the mixed MCT and LCT groups with regard to release of leucine from protein breakdown (B; 309+/-40 compared with 257+/-46 micromol x kg(-1) x h(-1)) and nonoxidative leucine disposal (NOLD; 296+/-36 compared with 285+/-49 micromol x kg(-1) x h(-1)). In contrast, leucine oxidation was greater in the mixed MCT than in the LCT group (113+/-10 compared with 67+/-10 micromol x kg(-1) x h(-1); P = 0.007). Net leucine balance (NOLD - B) was less positive in the mixed MCT than in the LCT group (-14+/-9 compared with 28+/-10 micromol x kg(-1) x h(-1); P = 0.011). CONCLUSION: Mixed MCTs may not be as effective as LCT-containing emulsions in promoting protein accretion in parenterally fed preterm neonates.     

Relative bioavailability of carnitine supplementation in premature neonates

BACKGROUND: Carnitine is an important nutrient in the infant diet. We compared total plasma carnitine concentrations in premature neonates supplemented with carnitine via parenteral and enteral nutrition. METHODS: This is a post hoc analysis of plasma total carnitine concentrations and carnitine intake in neonates randomized in a previous study to receive 20 mg/kg/d carnitine supplementation over 8 weeks. Neonates received l-carnitine initially via parenteral nutrition (PN). When neonates were fed enterally, oral supplementation of l-carnitine was given in divided doses with each feeding. RESULTS: Sixteen neonates (27 +/- 2 weeks gestation; 2.9 +/- 1.0 days postnatal age at enrollment; 965.6 +/- 279.1 g birth weight) are included. Concentrations were below reference range (31.1-60.5 nmol/mL) at baseline and exceeded reference range from week 1 through the last study period. Concentrations were not different from week 1 (108 +/- 49) through weeks 4 (87 +/- 34) and 8 (83 +/- 31). Carnitine intakes and concentrations were compared in neonates receiving 100% parenteral carnitine at week 1 (n = 6) and 100% enteral carnitine at week 8 (n = 8). Concentrations at week 1 (100.1 +/- 27.9) were not different (p = .19) from week 8 (78.6 +/- 29.3); an estimate of relative bioavailability was 78.6%. Bioavailability with paired analysis of neonates (n = 5) receiving 100% parenteral carnitine at week 1 and 100% enteral carnitine at week 8 was 83.7% +/- 41.2% (30.1%-140.6%). CONCLUSIONS: Parenteral and enteral supplementation of 20 mg/kg/d carnitine results in plasma total carnitine concentrations that exceed the reference range. Concentrations are not different between parenteral to enteral supplementation, suggesting that enteral carnitine is well absorbed when given daily in divided doses with enteral feedings.     

Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids

BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment. OBJECTIVE: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs. DESIGN: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs, which were derived from linoleic and alpha-linolenic acids. The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated. RESULTS: Percentage AA synthesis was 67.2 +/- 7.8%, 35.9 +/- 9.8%, and 29.0 +/- 10.3%, and that of DHA was 41.7 +/- 14.9%, 10.5 +/- 8.1%, and 7.4 +/- 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 +/- 4.2, 14.4 +/- 3.9, and 11.6 +/- 4.1 mg x kg(-1) x d(-1) and that of DHA was 12.6 +/- 4.5, 3.2 +/- 2.5, and 2.3 +/- 1.9 mg x kg(-1) . d(-1) at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis. CONCLUSIONS: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs.     

Effects of wine intake on postprandial plasma amino acid and protein kinetics in type 1 diabetes

BACKGROUND: Alcohol may impair protein turnover and insulin sensitivity in vivo. OBJECTIVE: The acute effects of moderate wine intake on amino acid kinetics and on the fractional synthetic rate (FSR) of albumin and fibrinogen in patients with type 1 diabetes were studied. DESIGN: Six patients with type 1 diabetes ingested an elementary mixed meal (46 kJ/kg) over 4 h, first without and 3 mo later with approximately 300 mL red wine. Postprandial glucose concentrations were maintained at <10 mmol/L. RESULTS: Postprandially, the FSR of fibrinogen was approximately 30% greater (21.5 +/- 6.6% compared with 14.1 +/- 3.6% of pool/d; P < 0.01) and glucagon concentrations were approximately 40% greater (103 +/- 20 compared with 61 +/- 13 ng/L; P < 0.015) with wine than without wine. However, the FSR of albumin and the rates of appearance of total and endogenous phenylalanine and leucine were not significantly different between treatments. First-pass splanchnic uptake (in micromol*kg(-1)*min(-1)) of dietary phenylalanine (0.22 +/- 0.02 compared with 0.19 +/- 0.02) and leucine (0.25 +/- 0.04 compared with 0.14 +/- 0.02) were greater with wine (P < 0.05), whereas dietary phenylalanine oxidation was lower with wine, by approximately 25% (0.10 +/- 0.02 compared with 0.14 +/- 0.01 micromol.kg(-1).min(-1); P < 0.05). Selected amino acid concentrations were significantly lower but glutamate concentrations were significantly higher with wine. CONCLUSIONS: In insulin-infused patients with type 1 diabetes, moderate wine intake with a meal resulted in 1) a higher fibrinogen FSR, glucagon concentration, and first-pass splanchnic uptake of leucine and phenylalanine; 2) lower dietary phenylalanine oxidation; 3) selective changes in plasma amino acid concentrations; 4) and no impairment in endogenous proteolysis and albumin synthesis.     

The methionine requirement is lower in neonatal piglets fed parenterally than in those fed enterally

The requirements for the sulfur amino acids (SAA), methionine (Met) and cysteine (Cys), have seldom been determined in neonates and to our knowledge have not previously been determined directly in parenterally fed neonates. The sulfur amino acids are catabolized largely in the liver and kidney, and their metabolism by the gut has been studied less frequently. In the present research, the enteral and parenteral Met requirement was determined, without dietary Cys, using the indicator amino acid oxidation (IAAO) technique. Piglets [n = 32, 2 d old, 1.66 +/- 0.13 kg (SD)] received elemental diets containing adequate energy, phenylalanine (Phe) and excess tyrosine, with varied Met concentrations and no Cys. Diets were infused continuously via intravenous or intragastric catheters. Phenylalanine oxidation was determined during a primed, constant infusion of L-[1-(14)C]-Phe, by measuring expired (14)CO(2) and plasma specific radioactivity of Phe. For both parenteral and enteral groups, Phe oxidation (% of dose) decreased linearly (P < 0.01) as Met intake increased, then became low and unchanging. Using breakpoint analysis, the Met requirement was estimated to be 0.42 and 0.29 g/(kg. d) for enteral and parenteral feeding, respectively. Breakpoint analysis using absolute phenylalanine oxidation [ micro mol/(kg. h)] resulted in an estimation of the Met requirement of 0.44 and 0.26 g/(kg. d) for enteral and parenteral feeding, respectively. These data show that the parenteral Met requirement is approximately 69% of the enteral requirement and suggest that extraction of SAA by first-pass splanchnic metabolism may be responsible for this difference.     

Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition

Continuous infusion of insulin was used to improve glucose tolerance in 30 premature (26.4+/-1.4 weeks) very-low-birth-weight (750+/-211.3 g) hyperglycaemic infants receiving parenteral nutrition. Infusion of insulin was started at 159.1+/-67 h of life; while glycaemia was 12.1+/-3.3 mmol/l. Normoglycaemia was restored within 31.4h (range 2-134 h). A maximum insulin dose of 0.4 (range 0.07-4.2)IU/kg/h was required to control the blood glucose, the mean cumulative doses of insulin required was 3.27 IU/kg (range 0.09-18.1). The mean glucose infusion rate during insulin treatment was 20.3+/-1.7 g/kg/day; lipid was 4.6+/-1.1 g/kg/day and non-protein caloric intake 121.7+/-16.5 kcal/kg/day. Infants reach 85 kcal/kg/day of non-protein energy intake at 179.5+/-71.2 h after birth. During continuous insulin infusion, enteral feeding was started in all infants at 124.9+/-75.8 h of life. Insulin was continued for 317.7+/-196.6 h. Only two infants lost weight during the first week of treatment, the remaining infant gained weight steadily. In conclusion, continuous insulin infusion can rapidly and safely improve intravenous glucose tolerance, allowing higher caloric intake and growth in very-low-birth-weight infants who develop hyperglycaemia during total parenteral nutrition.     

Glucose kinetics and splanchnic uptake following mixed meal ingestion in cirrhotic-diabetic subjects

Although glucose intolerance and/or overt diabetes are common in cirrhotic subjects, the mechanism(s) that lead to post-prandial hyperglycemia in cirrhosis are not entirely known. To this aim, we measured whole-body rates of glucose appearance (Ra) and of disappearance (Rd) in cirrhotic-diabetic subjects and in controls, before and following a 4-hr administration of a mixed meal. In the post-prandial phase, endogenous and dietary glucose Ra, as well as first-pass splanchnic uptake of dietary glucose, were measured using a double (ie oral and intravenous) glucose tracer technique. In the fasting state, the cirrhotic patients were hyperglycemic (12.0 +/- 1.4 vs 4.4 +/- 0.2 mmol/l in controls, p < 0.001), had a higher glucose Ra (17.0 +/- 2.7 vs 10.2 +/- 0.5 micromol x kg(-1) x min(-1), p < 0.05) and a lower clearance rate (1.51 +/- 0.19 vs 2.32 +/- 0.06 ml x kg x min, p < 0.02). Following the meal, plasma glucose increased to greater values (p < 0.002) in the patients (to 16.8 +/- 2 mmol/l, mean values of the last 40 min) than in the controls (to 7.2 +/- 0.4 mmol/l). Insulin increased in both groups but it was 35% lower (p > 0.05) in the patients. Post-prandial total glucose Ra (cirrhotics: 21.3 +/- 2.6; controls: 19.2 +/- 1.4 pmol x kg(-1) x min(-1)), endogenous Ra (cirrhotics: 7.3 +/- 1.5; controls: 7.0 +/- 1.3 micromol x kg(-1) x min(-1)) and first-pass splanchnic uptake of dietary glucose (cirrhotics: 9.8 +/- 2.6; controls: 11.5 +/- 1.6 micromol x kg x min(-1)), were not different between the 2 groups, whereas glucose clearance remained lower (p<0.001) in the patients (1.31 +/- 0.25 ml x kg(-1) x min)-1)) than in the controls (2.72 +/- 0.26). These data demonstrate that, in cirrhotic-diabetic patients, post-pran-dial hyperglycemia is not due to a reduced extraction of dietary glucose nor to an increased endogenous production, but rather to a defect in peripheral glucose clearance, secondary to either insulin-resistance and/or relative insulin deficiency.     

Macronutrients and Micronutrients in Parenteral Nutrition for Preterm Newborns: A Narrative Review

Preterm neonates display a high risk of postnatal malnutrition, especially at very low gestational ages, because nutritional stores are less in younger preterm infants. For this reason nutrition and growth in early life play a pivotal role in the establishment of the long-term health of premature infants. Nutritional care for preterm neonates remains a challenge in clinical practice. According to the recent and latest recommendations from ESPGHAN, at birth, water intake of 70–80 mL/kg/day is suggested, progressively increasing to 150 mL/kg/day by the end of the first week of life, along with a calorie intake of 120 kcal/kg/day and a minimum protein intake of 2.5–3 g/kg/day. Regarding glucose intake, an infusion rate of 3–5 mg/kg/min is recommended, but VLBW and ELBW preterm neonates may require up to 12 mg/kg/min. In preterm infants, lipid emulsions can be started immediately after birth at a dosage of 0.5–1 g/kg/day. However, some authors have recently shown that it is not always possible to achieve optimal and recommended nutrition, due to the complexity of the daily management of premature infants, especially if extremely preterm. It would be desirable if multicenter randomized controlled trials were designed to explore the effect of early nutrition and growth on long-term health.     

Selenium status in term and preterm infants during the first months of life

OBJECTIVE: We hypothesized that very low birth weight (VLBW) infants have reduced serum and red blood cell (RBC) selenium (Se) at birth, which decrease further with current nutrition and are associated with chronic lung disease and septicaemia. DESIGN: We studied Se intake, concentration in serum and RBCs and glutathione peroxidase (GSH-Px) activity in preterm and term infants from birth until 16 weeks. Data are mean+/-standard deviation (s.d.). SETTING: Seventy-two preterm infants in two groups, born in Berlin, gestational age 26+0/30+0 weeks, birth weight 845/1270 g, with low Se intake (2.2+/-0.8/2.5+/-1.2 microg/kg/day), and 55 term infants, gestational age 39+1 weeks, birth weight 3160 g, born in Venezuela (high Se intake: 29+/-8 microg/day). RESULTS: A balance study in 10 preterm infants showed that Se is well absorbed from human milk (77+/-9%). Serum concentration was higher in term (142.0+/-40.0 microg/l) than in preterm infants (17.8+/-8.1/19.9+/-2.2 microg/l) at 4/7 weeks. Serum and RBC concentration of Se declined in all infants, low values in preterm infants did not correlate with chronic lung disease and septicaemia. GSH-Px activity in RBCs remained stable until 6 weeks of age in all infants and was not correlated with Se in RBCs. CONCLUSIONS: Se concentration in serum decreases during the first weeks of life and depends on intake. GSH-Px activity is not useful as a marker for Se status in infants up to 16 weeks after birth.     

Effects of enteral carbohydrates on de novo lipogenesis in critically ill patients

BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a possible fate of carbohydrate administered during nutritional support. It cannot be detected by conventional methods such as indirect calorimetry if it does not exceed lipid oxidation. OBJECTIVE: The objective was to evaluate the effects of carbohydrate administered as part of continuous enteral nutrition in critically ill patients. DESIGN: This was a prospective, open study including 25 patients nonconsecutively admitted to a medicosurgical intensive care unit. Glucose metabolism and hepatic DNL were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate. RESULTS: DNL increased with increasing carbohydrate intake (f1.gif" BORDER="0"> +/- SEM: 7.5 +/- 1.2% with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate, and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations. Endogenous glucose production, assessed with a dual-isotope technique, was not significantly different between the 3 groups of patients (13.7-15.3 micromol * kg(-1) * min(-1)), indicating impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with [(13)C]bicarbonate, and increased as the carbohydrate intake increased (from 2.1 +/- 0.5 micromol * kg(-1) * min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3 micromol * kg(-1) * min(-1) with 75% carbohydrate intake, P: < 0. 05). CONCLUSION: Carbohydrate feeding fails to suppress endogenous glucose production and gluconeogenesis, but stimulates DNL in critically ill patients.     

Moderate disaccharide malabsorption does not affect weight gain and cecal cell proliferation in piglets

BACKGROUND: Intestinal malabsorption of disaccharides or oligosaccharides occurs normally in preterm infants, the majority of the world's adult population when ingesting dairy products, and in sick patients with abnormal intestinal motility or intestinal damage. Although there may be benefit to colonic fermentation, there also could be mucosal damage from excessive fermentation. Moreover, excess fluid in the colon also may impair fermentation. There are few data that address the effects of moderate amounts of carbohydrate, such as 50% of intake, reaching the colon. We addressed the hypothesis that normal weight gain and stool characteristics would occur during disaccharide malabsorption approximating 50% of intake. METHODS: Twelve piglets (aged 17 days) were randomized to receive control sow milk replacement formula (CON; lactose 60 g/L) or CON modified so that lactulose replaced 50% of the lactose (LAC). During a 5- to 7-day period, weight gain and fecal characteristics were observed before autopsy for cecal histology and determination of cecal cell proliferation using bromodeoxyuridine. RESULTS: Neither group developed diarrhea. In LAC and CON, formula intakes (g/kg/d) were similar (279 +/- 30 and 280 +/- 35), as were the ratios of weight gain:formula intake (g/mL): 0.23 +/- 0.04 and 0.22 +/- 0.04. Mean cecal cell proliferation was not diminished in the group receiving lactulose (p > .05). CONCLUSION: These data suggest that moderate (50%) disaccharide malabsorption per se does not cause diarrhea and does not impair dietary energy use or colonic cell proliferation.     

Evaluation of transthyretin as a monitor of protein-energy intake in preterm and sick neonatal infants

In the past, weight and weight gain have been the two parameters used frequently in neonatal units to monitor nutrition among high-risk infants. Our investigation sought to assess how several anthropometric measures (weight, length, head circumference, arm:head circumference ratio, and tricep skinfold) and serum albumin, transthyretin, and transferrin concentrations reflect protein and energy intake. After monitoring 42 preterm and 40 sick infants over 3 consecutive weeks, we found that transthyretin concentration proved the only serum protein which accurately measured energy and protein intakes in less than 1 week from dietary manipulation. Among preterm infants, as protein and energy intakes rose, transthyretin concentration increased significantly (p less than 0.001). Preterm infants ingested 79 +/- 39 kcal/kg/day and 2.04 +/- 1.02 g protein/kg/day at the first assessment point after birth and rose to 103 +/- 34 kcal/kg/day and 2.64 +/- 0.94 g protein/kg/day. Likewise, transthyretin measured 10.83 +/- 3.91 mg/dl at the initial measurement and rose to 14.80 +/- 4.44 at the second measurement time. Although protein intakes measured slightly lower in the sick group, their intakes correlated to transthyretin concentration (assessment time 1, r = 0.39; time 2, r = 0.33; time 3, r = 0.33). Thus, transthyretin concentration in neonatal infants offers a rapid, accurate, and moderately inexpensive way to monitor protein-energy adequacy.     

Net calcium absorption in premature infants: results of 103 metabolic balance studies.

Net calcium absorption was evaluated in 103 low-birth-weight preterm infants by a 72-h balance technique. At birth the infants had a mean (+/- SE) gestational age of 30.9 +/- 0.2 wk and weighed 1.43 +/- 0.03 kg. When tested 3 wk later, their net calcium absorption averaged 58 +/- 1% with an intake of 80 +/- 2 mg Ca.kg body wt-1.d-1. Of the 103 infants, 58 had been fed low-birth-weight formulas supplemented with vitamin D. The remainder received banked human milk, of whom 34 were supplemented with vitamin D and calcium; 11 infants received no supplementation. Calcium absorption in the four subgroups did not differ significantly, with neither vitamin D supplementation nor supplementation with vitamin D and calcium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-130 mg Ca.kg body wt-1.d-1) with a zero intercept. Because vitamin D supplementation did not increase net calcium absorption, it is concluded that in preterm low-birth-weight infants calcium absorption proceeds by a nonsaturable route, with the transcellular, vitamin D-regulated mechanism not yet expressed.     

Glutamine supplementation in infants with gastrointestinal disease: a randomized, placebo-controlled pilot trial

OBJECTIVE: Glutamine (Gln) is a non-essential amino acid that plays an important role in energy metabolism for gastrointestinal epithelia and other cells with rapid turnover. We evaluated the effects of enteral supplementation with Gln in infants undergoing surgery for congenital or acquired gastrointestinal disease. METHODS: This was a randomized, double-masked, controlled clinical trial. RESULTS: Twenty infants were randomly assigned to receive Gln (n = 9) or placebo amino acid (n = 11), with a goal of supplemental amino acid intake of 0.4 g.kg(-1).d(-1). Infants were weaned from parenteral nutrition, and enteral feeds were started according to a standardized feeding protocol. Median (interquartile range) durations of parenteral nutrition were 39 d (12 to 99) in the Gln group and 21 d (6 to 59) in the control group (P = 0.201). Median (interquartile range) durations needed to reach 80% of the US recommended dietary allowance for energy with enteral nutrition were 24 d (8 to 55) in the Gln group and 12.5 d (5 to 32) in the control group (P = 0.313). There were no differences in the occurrence of infections between groups. Among all infants enrolled, significant correlations were found between duration of parenteral nutrition and residual small bowel length, peak concentrations of direct bilirubin, and alanine aminotransferase. Peak direct bilirubin was associated with longer duration of parenteral nutrition, shorter gestation, older age before feeds were started, shorter bowel length, and larger amounts of parenteral energy and protein intake. CONCLUSIONS: In this pilot trial, enteral Gln supplementation was well tolerated among infants with surgical gastrointestinal disease. There was no effect observed on the duration of parenteral nutrition, tolerance of enteral feeds, or intestinal absorptive or barrier function. Larger, multicenter trials in infants with surgical gastrointestinal disease are needed due to the variability in important outcome measurements.     

Dietary fat content alters insulin-mediated glucose metabolism in healthy men

BACKGROUND: A high dietary fat intake is involved in the pathogenesis of insulin resistance. OBJECTIVE: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. DESIGN: Six healthy men were studied on 3 occasions after consuming for 11 d diets with identical energy and protein contents but different percentages of energy as fat and carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41% and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2% [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by using a hyperinsulinemic euglycemic clamp (plasma insulin concentration: approximately 190 pmol/L). RESULTS: During hyperinsulinemia, endogenous glucose production was higher after the HFLC diet (2.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) than after the IFIC and LFHC diets (1.7 +/- 0.3 and 1.2 +/- 0.4 micromol x kg(-1) x min(-1), respectively). The ratio of dietary fat to carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in relation to an increase in the ratio of fat to carbohydrate, from 14.8 +/- 5.1 to 20.6 +/- 1.9 to 26.2 +/- 2.9 micromol x kg(-1) x min(-1) (P < 0.074 between the 3 diets). Insulin-stimulated glucose oxidation was significantly lower after the HFLC diet than after the IFIC and LFHC diets: 1.7 +/- 0.8 compared with 13.4 +/- 2.1 and 19.0 +/- 2.1 micromol x kg(-1) x min(-1), respectively (P < 0.05). During the clamp study, plasma fatty acid concentrations were higher after the HFLC diet than after the IFIC and LFHC diets: 0.22 +/- 0.02 compared with 0.07 +/- 0.01 and 0.05 +/- 0.01 mmol/L, respectively (P < 0.05). CONCLUSION: A high-fat, low-carbohydrate intake reduces the ability of insulin to suppress endogenous glucose production and alters the relation between oxidative and nonoxidative glucose disposal in a way that favors storage of glucose.     

Splanchnic Tissue Oxygenation for Predicting Feeding Tolerance in Preterm Infants

Background: Feeding intolerance is very frequent in preterm infants, and the development of an early effective biomarker for its prediction could be useful for carrying out a proper feeding strategy. Our aim was to evaluate if the measurement of splanchnic regional oxygenation (rSO₂S) and splanchnic fractional oxygen extraction ratio (FOES) using near‐infrared spectroscopy (NIRS) is correlated with the time needed to achieve full enteral feeding and if it can predict the development of feeding intolerance. Materials and Methods: We measured rSO₂S and FOES in preterm infants 25 ± 0 to 31 ± 6 weeks of gestational age at 24–72 hours of life during continuous enteral feeding. Results: Linear regression analysis did not evidence any relationship between rSO₂S and FOES and the time for achievement of full enteral feeding. Multivariate logistic regression analysis showed that birth weight <1000 g (relative risk [RR], 4.5; 95% confidence interval [CI], 1.23–16.45) and patent ductus arteriosus occurrence (RR, 9.3; 95% CI, 1.31–66.06) increased the risk of developing feeding intolerance in our population. Conclusion: Splanchnic oxygenation and oxygen extraction measured in the first days of life are not correlated with the time needed to achieve full enteral feeding in preterm infants receiving continuous enteral nutrition.     

Splanchnic metabolism of ingested amino acids in neonates

PURPOSE OF REVIEW: Neonates typically show rapid growth. Nutrient absorption in the neonatal period is higher than during any other time in life so as to meet the requirements for this rapid growth. Generally, nutrients are administered enterally, and in the past the gut was considered to absorb and digest these nutrients without major metabolism. Recent animal and human work has, however, revealed that the intestine and other splanchnic tissues contribute significantly to whole-body metabolism, and have their own specific functions. This review focuses on these observations. RECENT FINDINGS: The splanchnic tissues take up greatly different proportions of each of the amino acids, ranging from 80-100% for threonine and several nonessential amino acids to 15-30% for lysine. The metabolic fates of the utilized substrates differ as well. Some are predominantly used for constitutive protein synthesis, others for energy generation or for formation of (glyco-)proteins that are secreted into the lumen. Glucose appears to be the major contributor to energy generation, but amino acids are important as well. SUMMARY: Both animal and human studies have shown that the intestine uses substantial amounts of dietary amino acids. This has several implications for the nutritional needs of infants to maintain growth, especially during times of inadequate enteral nutrition.     

A 9-mo randomized clinical trial comparing fat-substituted and fat-reduced diets in healthy obese men: the Ole Study

BACKGROUND: Dietary fat has been implicated as a risk factor for cardiovascular disease and obesity. OBJECTIVE: We evaluated the effect on body weight, body fat, lipids, glucose, and insulin of replacing dietary fat with olestra in moderately obese men. DESIGN: Forty-five healthy overweight men were randomly assigned to 1 of 3 diets: control diet (33% fat), fat-reduced diet (25% fat), or fat-substituted diet (one-third of dietary fat replaced by olestra to achieve a diet containing 25% metabolizable fat). Body fat was measured by dual-energy X-ray absorptiometry and visceral and subcutaneous abdominal fat by computed tomography. RESULTS: Thirty-six men completed the 9-mo study. Body weight and body fat in the fat-substituted group declined by a mean (+/- SEM) of 6.27 +/- 1.66 and 5.85 +/- 1.34 kg, respectively, over 9 mo compared with 3.8 +/- 1.34 and 3.45 +/- 1.0 kg in the control group and 1.79 +/- 0.81 and 1.68 +/- 0.75 kg in the fat-reduced diet group. At 9 mo, the mean difference in body fat between the fat-reduced and fat-substituted groups was -4.19 +/- 1.19 kg (95% CI: -6.57, -1.81), that between the control and fat-substituted groups was -2.55 +/- 1.21 kg (-0.13, -4.97), and that between the control and fat-reduced groups was 1.63 +/- 1.18 kg (3.96, -0.70). The men eating the fat-reduced diet asked for almost no extra foods, in contrast with the significantly higher requests (P < 0.05) from both of the other 2 groups. CONCLUSION: Replacement of dietary fat with olestra reduces body weight and total body fat when compared with a 25%-fat diet or a control diet containing 33% fat.     

Hepatic de novo lipogenesis in stable low-birth-weight infants during exclusive breast milk feedings and during parenteral nutrition

BACKGROUND: Low-birth-weight (LBW) infants have high energy requirements and are dependent on high fat intake to maintain adequate postnatal growth. Fat energy is transported in plasma as triglycerides, which are either derived from the diet or from de novo lipogenesis (DNL). It is our hypothesis that DNL plays an important physiologic role in adapting to exclusive breast milk (EBM) feeding or to parenteral nutrition (PN). METHODS: We studied hepatic de novo lipogenesis in 14 LBW (<34-week gestation) appropriate for gestational age and receiving either EBM feedings or full PN support. Stable isotope tracer [2-(13)C] acetate was administered for 72 hours to achieve an estimated 10% enrichment of daily fat intake. Fatty acids were extracted from plasma for gas chromatography-mass spectrometry analyses. RESULTS: Percent new synthesis of palmitate was 13.1% +/- 2.5% in the EBM group and 14.9% +/- 0.7% in the PN group (NS), stearate was 11.1% +/- 2.7% in the EBM group and 10.6% +/- 14% in the PN group (NS) and cholesterol was 12.7% +/- 2.1% in the EBM group and 17.4% +/- 4.6% in the PN group (NS) after 72 hours of tracer administration (mean +/- SEM). The plasma lipid fatty acid composition in palmitate, oleate, and stearate with intake of 3.6 +/- 0.6 g/kg/d of IV lipids (ILs) was similar to EBM-feeding infants taking 6.3 +/- 0.13 g/kg/d of fat. CONCLUSIONS: De novo lipogenesis is active in stable LBW infants maintaining standard postnatal growth. Hepatic DNL permits newborn infants to meet the fat energy needs of peripheral tissues for growth and storage and to maintain plasma fatty acid composition in adaptation to different dietary fat intake.