Prospective analysis of serum carotenoids, vitamin A, and tocopherols in adults with short bowel syndrome undergoing intestinal rehabilitation.

OBJECTIVE: Carotenoids, vitamin A, and tocopherols serve important roles in many key body functions. However, availability of these compounds may be decreased in patients with short bowel syndrome (SBS) due to decreased oral intake of fruits and vegetables and/or decreased intestinal absorption. Little information is available on serum concentrations of carotenoids, vitamin A, and tocopherols during chronic parenteral nutrition (PN) or during PN weaning. The aim of this study was to prospectively examine serum concentrations of a wide variety of carotenoids, vitamin A, and tocopherols in patients with SBS undergoing an intensive 12-wk intestinal rehabilitation program. METHODS: Twenty-one PN-dependent adult patients with SBS were enrolled in a 12-wk intestinal rehabilitation program, which included individualized dietary modification, multivitamin supplementation, and randomization to receive subcutaneous placebo (n = 9) or human growth hormone (0.1 mg . kg(-1) . d(-1); n = 12). PN weaning was initiated after week 4 and advanced as tolerated. Serum concentrations of carotenoids, vitamin A, and tocopherols were determined at baseline and at weeks 4 and 12. RESULTS: A significant percentage of subjects exhibited low serum concentrations for carotenoids and alpha-tocopherol at study entry, and a few subjects had low concentrations of retinol (5%). Carotenoid and vitamin A valves did not improve over time, while alpha-tocopherol levels rose. Serum alpha-tocopherol concentration was negatively associated with PN lipid dose (r = -0.34, P < 0.008). CONCLUSION: Patients with SBS are depleted in diet-derived carotenoids despite oral and intravenous multivitamin supplementation and dietary adjustment during intestinal rehabilitation and PN weaning. Reduction of PN lipid infusion may improve serum alpha-tocopherol concentrations.

Nutrient intake from habitual oral diet in patients with severe short bowel syndrome living in the southeastern United States.

OBJECTIVES: Little data are published on the habitual home oral diet of patients with short bowel syndrome (SBS). METHODS: We assessed nutrient intake from oral food and beverages in 19 stable patients with severe SBS who live in the southeastern United States. Intestinal absorption of energy, fat, nitrogen (N), and carbohydrate (CHO) was determined in a metabolic ward. RESULTS: We studied 12 women and 7 men, age 48 +/- 3 y of age (mean +/- SE) receiving parenteral nutrition for 31 +/- 8 mo following massive small bowel resection (118 +/- 25 cm residual small bowel). The patients demonstrated severe malabsorption of energy (59 +/- 3% of oral intake), fat (41 +/- 5%), N (42 +/- 5%) and CHO (76 +/- 3%). Oral energy intake was 2656 +/- 242 kcal/d (39 +/- 3 kcal/kg/d) and oral protein intake was 1.4 +/- 0.1 g/kg/d. Food/beverage intake constituted 49 +/- 4% of total (enteral plus parenteral) daily fluid intake, 66 +/- 4% of total daily kcal and 58 +/- 5% of total daily N intake. Oral fat intake averaged 92 +/- 11 g/day ( approximately 35% of total oral energy). Oral fluid intake averaged 2712 +/- 240 ml/d, primarily from water, soft drinks, sweet tea and coffee. Simple sugars comprised 42 +/- 3% of oral CHO intake. Usual dietary intake of multiple micronutrients were below the Recommended Dietary Allowances (RDA) in a large percentage of patients: vitamin A (47%), vitamin D (79%), vitamin E (79%), vitamin K (63%), thiamine (42%), vitamin B6 (68%), vitamin B12 (11%), vitamin C (58%), folate (37%), iron (37%), calcium (63%), magnesium (79%) and zinc (68%). Only seven patients (37%) were taking oral multivitamin-mineral supplements and only six subjects (32%) were taking oral iron and calcium supplements, respectively. CONCLUSION: In these SBS patients, an oral diet provided a significant proportion of daily nutrient intake. The types of foods and fluids consumed are likely to worsen malabsorption and thus increase PN requirements. Oral intake of essential micronutrients was very low in a significant proportion of these individuals.

Depletion of plasma antioxidants in surgical intensive care unit patients requiring parenteral feeding: effects of parenteral nutrition with or without alanyl-glutamine dipeptide supplementation.

OBJECTIVES: Antioxidant depletion is common in critically ill patients. This study was designed to determine the effects of parenteral nutrition (PN), with or without glutamine (Gln) supplementation, on systemic antioxidant status in adult patients after major surgery who required PN in the surgical intensive care unit (SICU) setting. METHODS: Fifty-nine patients in the SICU who required PN after pancreatic surgery or cardiac, vascular, or colonic (non-pancreatic) surgery were randomized in a double-blinded study to receive standard PN (Gln-free) or Gln-supplemented PN (Gln-PN) in which Gln was provided as alanyl-Gln dipeptide. Conventional PN vitamin and mineral doses were administered to all subjects. Plasma concentrations of the antioxidant glutathione (GSH) and the antioxidant nutrients alpha-tocopherol, vitamin C, and zinc were determined at baseline (initiation of study PN) and again after 7 d of study PN. Data were analyzed for the total study cohort and within the pancreatic surgery and non-pancreatic (cardiac, vascular, and colonic) surgery patient subgroups. RESULTS: Mean plasma antioxidant concentrations were within or slightly below the normal ranges at baseline. However, a larger percentage of patients demonstrated below-normal baseline plasma concentrations of GSH (59%), vitamin C (59%), and zinc (68%), respectively. A smaller percentage of patients exhibited below-normal plasma alpha-tocopherol levels (21%). Study PN significantly improved plasma zinc levels in the entire study group and in each surgical subgroup. Gln-PN significantly improved the change in plasma levels of reduced GSH from baseline to day 7 in the non-pancreatic surgery patients (PN -0.27 microM versus Gln-PN +0.26 microM, P < 0.03). CONCLUSION: Low plasma levels of key antioxidants were common in this group of patients in the SICU despite administration of PN containing conventional micronutrients. Compared with standard PN, Gln-supplemented PN improved plasma GSH levels in patients in the SICU after cardiac, vascular, or colonic operations.

Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients.

BACKGROUND: Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. METHODS: This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. RESULTS: Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). CONCLUSIONS: Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?

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.

Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation.

BACKGROUND: Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. METHODS: Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. RESULTS: The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. CONCLUSIONS: hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.

Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes.

Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients; however, it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome. The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes. We reviewed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998. New hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 12% had no history of diabetes before the admission. Newly discovered hyperglycemia was associated with higher in-hospital mortality rate (16%) compared with those patients with a prior history of diabetes (3%) and subjects with normoglycemia (1.7%; both P < 0.01). In addition, new hyperglycemic patients had a longer length of hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility. Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.

Distribution of the H+/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome.

BACKGROUND: Intestinal adaptation after massive bowel resection in animal models is characterized by increased gut-mucosal growth and expression of nutrient transporters. Few data about these indexes exist in humans with short-bowel syndrome (SBS). OBJECTIVE: The objective was to compare small-bowel and colonic mucosal growth and expression of the peptide transporter PepT1 in adults with or without SBS. DESIGN: Mucosal biopsy specimens were obtained from the small bowel and colon of 33 control subjects with intact intestine and from 13 SBS patients dependent on parenteral nutrition because of chronic malabsorption. Gut-mucosal crypt depth, villus height, and villus width were measured, and expression of PepT1 was determined by Northern blotting, in situ hybridization, and immunohistochemistry. RESULTS: The indexes of small-bowel and colonic mucosal growth were not significantly different between the 2 groups. PepT1 expression was high in the apical region of duodenal, jejunal, and ileal villus epithelial cells; low in absorptive colonocytes; and not significantly different in the distal small intestine of the 2 groups. However, the abundance of PepT1 mRNA in the colon of SBS patients was more than 5-fold that in control subjects (P < 0.01). CONCLUSIONS: Gut adaptation in SBS patients does not appear to involve an increase in gut-mucosal crypt depth or villus size. PepT1 is abundant along the small-bowel brush border in humans; expression in the colon indicates that the large intestine has a mechanism for luminal di- and tripeptide transport. Up-regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed di- and tripeptides, independent of changes in the mucosal surface area.

Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study.

BACKGROUND: Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting. OBJECTIVES: We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation. METHODS: In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8. RESULTS: Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance. CONCLUSIONS: This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.

Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome.

Gut barrier dysfunction may occur in short bowel syndrome (SBS). We hypothesized that systemic exposure to flagellin and lipopolysaccharide (LPS) in SBS might regulate specific immune responses. We analyzed serial serum samples obtained from parenteral nutrition (PN)-dependent patients with SBS versus non-SBS control serum. Serum from 23 adult SBS patients was obtained at baseline and 4, 8, 12, 16, 20, and 24 wk in a trial of modified diet with or without growth hormone. Control serum was obtained from 48 healthy adults and 37 adults requiring PN during critical illness. Serum flagellin was detected by an ELISA recognizing an array of gram-negative flagellins, and LPS was detected by limulus assay. Serum flagellin- and LPS-specific immunoglobulin levels (IgM, IgA, and IgG) were determined by ELISA. Serum flagellin and LPS were undetectable in control subjects. In contrast, serum flagellin, LPS, or both were detected in 14 SBS patients (61%) during one or more time points [flagellin alone, 5/23 (22%); LPS alone, 6/23 (26%); or flagellin + LPS, 3/23 (13%)]. Flagellin-specific serum IgM, IgA, and IgG levels were markedly increased in SBS patients compared with both control populations and remained elevated during the 6-mo study period. LPS-specific IgA was significantly higher in SBS patients compared with healthy controls; LPS-specific IgM, IgA, and IgG levels each decreased over time in association with PN weaning. We conclude that adults with PN-dependent SBS are systemically exposed to flagellin and LPS, presumably from the gut lumen. This likely regulates innate and adaptive immune responses to these specific bacterial products.