Luo Menghua, Fernández-Estívariz Concepción, Manatunga Amita K, Bazargan Niloofar, Gu Li H, Jones Dean P, Klapproth Jan-Michael, Sitaraman Shanthi V, Leader Lorraine M, Galloway John R, Ziegler Thomas R
Department of Medicine, Emory Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia, USA.
JPEN J Parenter Enteral Nutr. 2007 Jan-Feb;31(1):1-7. doi: 10.1177/014860710703100101.
Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared to be an indicator of small intestinal length in adult SBS. However, neither plasma Cit nor Gln was a biomarker for intestinal absorptive function in this cohort of patients with SBS.
用于评估肠道吸收功能的敏感生物标志物在短肠综合征(SBS)的临床应用中具有重要价值。瓜氨酸(Cit)是肠细胞对谷氨酰胺(Gln)及其他衍生氨基酸进行代谢的产物。Cit几乎完全由肠道产生,而肠道也是Gln代谢的主要场所。本研究的目的是前瞻性地观察成年SBS患者血浆Cit和Gln浓度是否为残余小肠长度及营养物质吸收功能的生物标志物。我们在一项关于个体化饮食调整±重组人生长激素(GH)的双盲、随机试验中,研究了24例接受长期肠外营养(PN)的稳定成年重度SBS患者。在基线期的一周内,进行肠道吸收研究(液体、千卡、氮、脂肪、碳水化合物、钠、磷和镁的吸收百分比),并同时测定血浆Cit和Gln浓度。随后开始个体化饮食调整,并皮下注射安慰剂(n = 9)或GH(0.1 mg/kg每日×21天,然后每周3次;n = 15)进行治疗。第4周后开始尝试减少PN用量,并根据耐受情况持续24周。在第4周和第12周重复进行血浆氨基酸测定和营养物质吸收研究。基线时残余小肠长度与基线血浆Cit呈正相关(r = 0.467;p = 0.028)。然而,在任何时间点均未观察到绝对Cit或Gln浓度与营养底物吸收百分比之间存在显著相关性。同样,未观察到Cit或GLN浓度变化与营养物质吸收百分比变化之间的相关性(分别为基线与第4周和第12周)。到第12周和第24周时,分别有7例和13例患者完全停用PN。然而,基线血浆Cit或Gln在这些时间点并不能预测PN停用情况。我们得出结论,血浆Cit(而非Gln)浓度似乎是成年SBS患者小肠长度的一个指标。然而,在这组SBS患者中,血浆Cit和Gln均不是肠道吸收功能的生物标志物。