Whole body protein turnover in childhood Crohn's disease.

Thomas, A G; Miller, Vivien; Taylor, F. J. R.; Maycock, P F; Scrimgeour, Charles M.; Rennie, Michael J.

doi:10.1136/gut.33.5.675

Cited by 53 publications

(27 citation statements)

References 8 publications

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“…The effect of therapy for Crohn disease on protein metabolism has been studied in children. In children with active Crohn disease, protein breakdown decreased after treatment with either sulfasalazine or prednisolone (9). Similarly, we demonstrated reductions in protein breakdown 2 wk after a single dose of infliximab, an anti-TNF-␣ antibody, for the treatment of active Crohn disease (10).…”

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confidence: 62%

Corticosteroids Increase Protein Breakdown and Loss in Newly Diagnosed Pediatric Crohn Disease

2011

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Children with Crohn disease have altered growth and body composition. Previous studies have demonstrated decreased protein breakdown after either corticosteroid or anti-TNF-␣ therapy. The aim of this study was to evaluate whole body protein metabolism during corticosteroid therapy in children with newly diagnosed Crohn disease. Children with suspected Crohn disease and children with abdominal symptoms not consistent with Crohn disease underwent outpatient metabolic assessment. Patients diagnosed with Crohn disease and prescribed corticosteroid therapy returned in 2 wk for repeat metabolic assessment. Using the stable isotopes [d5] phenylalanine, [1-13 C] leucine, and [ 15 N 2 ] urea, protein kinetics were determined in the fasting state. Thirty-one children (18 controls and 13 newly diagnosed with Crohn disease) completed the study. There were no significant differences in protein breakdown or loss between patients with Crohn disease at diagnosis and controls. After corticosteroid therapy in patients with Crohn disease, the rates of appearance of phenylalanine (32%) and leucine (26%) increased significantly, reflecting increased protein breakdown, and the rate of appearance of urea also increased significantly (273%), reflecting increased protein loss. Whole body protein breakdown and loss increased significantly after 2 wk of corticosteroid therapy in children with newly diagnosed Crohn disease, which may have profound effects on body composition. (Pediatr Res 70: 484-488, 2011) C hildren with Crohn disease suffer from growth impairment before diagnosis, and despite therapy, continue to have growth difficulties which may persist to altered adult growth outcomes. At diagnosis, these children suffer from not only linear growth impairment but also deficits in lean body mass (1) and bone mineral density (2). These deficits may result from altered nutritional intake, malabsorption, and inflammation. A prospective observational study demonstrated increases in BMI and fat mass in the 2 y after diagnosis of pediatric Crohn disease; however, no significant change in lean body mass and persistent deficits in bone mineral content were observed (2). Emerging evidence suggests gender differences in body composition may exist in pediatric patients with Crohn disease. Females with Crohn disease may have more persistent lean body mass deficits than males (3). Current therapeutic strategies may not be resulting in significant and important improvements in lean body mass in these patients.Both malnutrition and inflammation may be observed in pediatric patients with Crohn disease, and they may have opposing effects on substrate metabolism. In patients with chronic malnutrition, there are marked reductions in whole body protein turnover (4), including protein synthesis and breakdown, and in urea excretion, a marker of protein loss (5). In these patients, adaptations to reduction in protein intake result in minimization of protein loss. However, inflammation leads to increased whole body protein metabolism. Injection of T...

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confidence: 62%

Corticosteroids Increase Protein Breakdown and Loss in Newly Diagnosed Pediatric Crohn Disease

2011

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“…However, the total glutamine profile and tissue glutamine utilisation only increased in the glutaminesupplemented patients. Patients with inflammatory bowel disease are in a state of catabolism (Thomas et al, 1992) and have an increased risk for development of malnutrition, especially during an acute exacerbation of the disease (Geerling et al, 1998). Indeed, a significant increase of serum urea and plasma phenylalanine concentrations in the control group alone suggests improved nitrogen balance in the glutamine group.…”

Section: Discussionmentioning

confidence: 99%

Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease

et al. 2005

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Background: Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing. Methods: A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (47 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio. Results: Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (D-lactulose/xylose ratio: 0.0170.05 (gln þ ) vs 0.0270.1 (glnÀ)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln þ group and three (25%) patients in the glnÀ group needed surgical intervention. Conclusion: Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.

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“…Studies on animals indicate that excess production of TNF-α and IL-9 inhibits bone growth by down-regulating osteoblast proliferation and enhances bone resorption by increasing osteoclast numbers. The anorexigenic effect of TNF-α, as well as the increase in protein catabolism and the fractional increase in acute phase protein synthesis by the liver, accentuate the deleterious effect of inflammation on growth [16, 19]. …”

Section: Impact Of Inflammationmentioning

confidence: 99%

“…This report reviews the data concerning growth failure in paediatric CD [1, 2, 3, 4, 5, 6], how it comes about [3, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21]and the effect of new therapeutic strategies [22, 23, 24, 25, 26, 27, 28, 29, 30, 31]. …”

Section: Introductionmentioning

confidence: 99%

Growth in Paediatric Crohn’s Disease

et al. 2002

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Growth failure (GF) is one of the major complications affecting children with inflammatory bowel disease. The faltering is temporary in 40–50% of cases and prolonged in 10–20% in Crohn’s disease (CD). Such failure is rare in children with ulcerative colitis (5%). This complication is often associated with retarded bone development and delayed onset of sexual maturation. The delayed linear growth has a variety of causes including insufficient intake due to anorexia and the inflammatory process with increased energy and protein expenditure. Other factors are increased intestinal loss, secondary hypopituitarism and treatment with steroids. Therapeutic strategies of CD in children have changed this last decade by introducing new therapeutic agents such as topic steroids, immunosuppressors, anti-TNF (antibody and notably in children enteral nutrition which has shown its efficacy in inducing remissions of active CD, restoring nutritional status and stimulation of linear growth. The results of a recent prospective multicentric study over 2 years in 82 CD show that severe GF (–2 SD) is initially present in 15% (n = 12), among them 11 remain < –2SD after 2 years of follow-up. Six patients who were on the normal range initially increased their GF during the follow-up (< –2SD) (total 21% < –2SD (n = 17) at 2 years). At inclusion in this group there was no difference in growth velocity, used of steroids, enteral nutrition or severity of CD as compared to the group with no GF. It suggests that new treatment strategy should be developed in the future for this specific complication of paediatric CD.

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Whole body protein turnover in childhood Crohn's disease.

Abstract: In order to investigate the effects of treatment on protein metabolism in childhood Crohn's disease whole body protein turnover was measured using a primed constant intravenous infusion of L-[1-'3C]leucine and mass spectrometry in 10

Cited by 53 publications

References 8 publications

Corticosteroids Increase Protein Breakdown and Loss in Newly Diagnosed Pediatric Crohn Disease

Corticosteroids Increase Protein Breakdown and Loss in Newly Diagnosed Pediatric Crohn Disease

Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease

Growth in Paediatric Crohn’s Disease

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