P.B. Mortensen

Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study

BACKGROUND High dose growth hormone, glutamine, and a high carbohydrate diet may improve intestinal function in short bowel patients. AIMS To investigate if growth hormone with glutamine and no change in diet improved intestinal function. PATIENTS AND METHODS Eight short bowel patients were randomised in a double blind crossover study between placebo and growth hormone (mean 0.12 mg/kg/day) with oral (mean 28 g/day) and parenteral glutamine (mean 5.2 g/day) for 28 days. Balance studies were performed at baseline and five days after placebo and treatment were terminated. Dietary energy, carbohydrate, and fat were maintained as usual. RESULTS Growth hormone with glutamine did not improve intestinal absorption of energy (baseline, placebo, treatment, mean: 46%, 48%, 46% of oral intake, respectively), carbohydrate (71%, 70%, 71%), fat (20%, 15%, 18%), nitrogen (27%, 18%, 19%), wet weight (37%, 39%, 31%), sodium (−16%, −16%, −36%), potassium (43%, 47%, 33%), calcium (−16%, −16%, −15%) or magnesium (−3%, 4%, 2%) compared with placebo or baseline (p>0.05) five days after treatment was terminated. All patients experienced adverse effects. CONCLUSIONS Combined high dose growth hormone and glutamine administered for four weeks did not improve intestinal absorption five days after treatment was terminated in short bowel patients on their usual diet.

Quality of life in patients receiving home parenteral nutrition

BACKGROUND/AIMS Quality of life is an important determinant of the effectiveness of health technologies, but it has rarely been assessed in patients receiving home parenteral nutrition (HPN). PATIENTS/METHODS The non-disease specific sickness impact profile (SIP) and the disease specific inflammatory bowel disease questionnaire (IBDQ) were used on a cohort of 49 patients receiving HPN, and the results compared with those for 36 non-HPN patients with either anatomical (<200 cm) or functional (faecal energy excretion >2.0 MJ/day (∼488 kcal/day)) short bowel. RESULTS In the HPN patients the SIP scores were worse (higher) overall (17 (13)%v 8 (9)%) and with regard to physical (13 (15)% v 5 (8)%) and psychosocial (14 (12)% v 9 (11)%) dimensions and independent categories (20 (12)% v 9 (8)%) compared with the non-HPN patients (means (SD); all p<0.001). The IBDQ scores were worse (lower) in the HPN patients overall (5.0 (4.3–5.7)v 5.6 (4.8–6.2)) and with regard to systemic symptoms (3.8 (2.8–5.4) v 5.2 (3.9–5.9)) and emotional (5.3 (4.4–6.2) v5.8 (5.4–6.4)) and social (4.3 (3.4–5.5) v4.8 (4.5–5.8)) function (median (25–75%); all p<0.05), but only tended to be worse with regard to bowel symptoms (5.2 (4.8–6.1)v 5.7 (4.9–6.4), p = 0.08). HPN also reduced quality of life in patients with a stoma, whereas a stoma did not reduce quality of life among the non-HPN patients. Female HPN patients and HPN patients older than 45 scored worse. CONCLUSION Quality of life is reduced in patients on HPN compared with those with anatomical or functional short bowel not receiving HPN, and compares with that reported for patients with chronic renal failure treated by dialysis.

The influence of a preserved colon on the absorption of medium chain fat in patients with small bowel resection

Background—Medium chain C8–C10 triglycerides (MCTs) improve fat absorption in short bowel patients. Effects on overall energy absorption remain unknown. Aims—To determine whether MCTs and medium chain fatty acids (MCFAs) are absorbed in the colon like the short chain fatty acids (SCFAs) or are lost in faeces similarly to long chain fatty acids (LCFAs). Methods—Nine small bowel resected patients without and 10 with a colon in continuity excreted 2–6 MJ/day and were randomised and crossed over between two high fat diets (10 MJ/day, 50% as fat), based on either long chain triglycerides (LCT) alone or equal quantities of LCT and MCT. Results—Patients with a colon absorbed C8–C10 fatty acids considerably better than patients without a colon at similar and extreme levels of LCFA malabsorption; the colonic impact on absorption of C14–18 fatty acids was negligible. MCT redoubled fat (MCT+LCT) absorption from 23% to 58% in patients with a colon, and increased overall bomb calorimetric energy absorption from 46% to 58%. The increase in fat absorption from 37% to 46% in patients without a colon did not improve overall energy absorption because malabsorption of carbohydrate and protein increased. Conclusion—In small bowel resected patients, the colon seems to serve as a digestive organ for medium chain fat, probably absorbed as MCFAs, perhaps because like the SCFAs, they are water soluble. Only patients with a colon gained from MCT treatment.

Impaired meal stimulated glucagon-like peptide 2 response in ileal resected short bowel patients with intestinal failure

BACKGROUND Glucagon-like peptide 2 (GLP-2) is a growth factor for the intestinal epithelium in rodents and may affect intestinal transit. AIMS To study the GLP-2 response to nutrient ingestion in seven short bowel patients with intestinal failure and seven controls. METHODS The patients and controls were admitted twice for two test meals after a night of fasting. Meal A was liquid (300 ml, 1.88 MJ); meal B was a regular breakfast (755 g, 3.92 MJ). Plasma samples were collected for 180 minutes; GLP-2 immunoreactivity was measured with an NH2 terminal specific radioimmunoassay. RESULTS Both meals elicited significant increases in plasma GLP-2 in controls. The magnitude and duration of the responses were dependent on the meal size: the maximum median (25–75%) increases after meal A and B were 24 (3–28) and 48 (33–56) pmol/l. Plasma GLP-2 returned to basal concentrations 180 minutes after meal A, but remained at 50% of peak values after meal B. In the patients neither meal significantly changed the GLP-2 concentration; the maximum median elevation after meal B was 5 (2–8) pmol/l. There were significant differences between patients and controls with respect to the GLP-2 responses to meals A and B. CONCLUSION Identification of GLP-2 as a tissue specific intestinal growth factor and demonstration of an impaired meal stimulated GLP-2 response in short bowel patients raises the possibility that GLP-2 administration may constitute a new therapeutic strategy, enhancing jejunal adaptation in ileum resected short bowel patients with intestinal failure.

Intestinal failure defined by measurements of intestinal energy and wet weight absorption

BACKGROUND AND AIMS Intestinal failure defined by the minimal energy and wet weight absorption required to avoid home parenteral nutrition (HPN) is not well described. Thus the aim of this study was to identify the minimal level of gut function necessary to avoid parenteral support using objective measurements of intestinal function. METHODS Energy (bomb calorimetry) and wet weight absorption were measured during 48 hour balance studies in 45 HPN patients with intestinal failure and in 44 non-HPN borderline patients with a short bowel or malabsorption exceeding 2 MJ/day. RESULTS In the non-HPN patients, the lower 5% confidence interval of the absorption of energy was 84% of the basal metabolic rate (BMR, the Harris-Benedict equations), equivalent to 4.9 MJ/day. Wet weight absorption was 1.4 kg/day. The HPN patients absorbed less of either or both. The non-HPN patients absorbed 24–86% (range) of the energy and 23–95% of the wet weight. Absorption in the HPN patients ranged from below 0% (net secretion) in patients with very short bowels to 100% absorption of an insufficient oral intake in patients with pseudo-obstruction. Non-HPN patients who absorbed less than half of their intake avoided HPN by hyperphagia (200–400% of BMR equivalent to 10–24 MJ/day, and 3–7 kg/day of wet weight). CONCLUSION Intestinal failure was accurately measured as absorption below 1.4 kg/day of wet weight and 84% of the calculated BMR (depending on weight, sex and age), which is equal to 4.9 MJ/day. Intestinal absorption, expressed as a percentage of intake, did not discriminate between patients with and without intestinal failure, except for patients who absorbed less than 25% of their intake.

Short-term Administration of Glucagon-like Peptide-2. Effects on Bone Mineral Density and Markers of Bone Turnover in Short-Bowel Patients with No Colon

Background: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of shortbowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. Methods: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 μg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. Results: Mean ± s x (SEM) percent changes in spinal and hip BMD were 1.1 ± 0.4% ( P < 0.05) and 1.9 ± 0.8% ( P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% ( P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. Conclusion: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.

Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2: Effects on Intestinal Morphology and Absorption, Renal Function, Bone and Body Composition, and Muscle Function

Background and aims. In a short-term study, Glucagon-like peptide 2 (GLP-2) has been shown to improve intestinal absorption in short bowel syndrome (SBS) patients. This study describes longitudinal changes in relation to GLP-2 treatment for two years. Methods. GLP-2, 400 micrograms, s.c.,TID, were offered, to eleven SBS patients keeping parenteral support constant. 72-hour nutritional balance studies were performed at baseline, weeks 13, 26, 52 during two years intermitted by an 8-week washout period. In addition, mucosal morphometrics, renal function (by creatinine clearance), body composition and bone mineral density (by DEXA), biochemical markers of bone turnover (by s-CTX and osteocalcin, PTH and vitamin D), and muscle function (NMR, lungfunction, exercise test) were measured. Results. GLP-2 compliance was >93%. Three of eleven patients did not complete the study. In the remaining 8 patients, GLP-2 significantly reduced the fecal wet weight from approximately 3.0 to approximately 2.0 kg/day. This was accompanied by a decline in the oral wet weight intake, maintaining intestinal wet weight absorption and urinary weight constant. Renal function improved. No significant changes were demonstrated in energy intake or absorption, and GLP-2 did not significantly affect mucosal morphology, body composition, bone mineral density or muscle function. Conclusions. GLP-2 treatment reduces fecal weight by approximately 1000 g/d and enables SBS patients to maintain their intestinal fluid and electrolyte absorption at lower oral intakes. This was accompanied by a 28% improvement in creatinine clearance.

Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection

Background and aims: Vitamin D deficiency is common in patients with small intestinal resection and may lead to secondary hypersecretion of parathyroid hormone (PTH), which in turn may result in increased bone turnover rate and loss of bone mineral. The aims of this study were to investigate the prevalence of vitamin D deficiency, as assessed by low serum concentrations of 25-hydroxyvitamin D (25(OH)D) in patients with small intestinal resection and to explore the relation of 25(OH)D to PTH, markers of bone turnover rate, and bone mineral density (BMD) in these patients. Patients: Forty two patients with small intestinal resection, a faecal energy excretion of more than 2.0 MJ/day, and a mean length of the remaining small intestine of 199 cm were included. Diagnoses were Crohn’s disease (n=35) and other (n=7). Methods: 25(OH)D was analysed by radioimmunoassay and bone turnover rate was assessed by measurement of serum osteocalcin, serum alkaline phosphatase, urine pyridinoline, and urine deoxypyridinoline. BMD was measured by dual energy x ray absorptiometry. Results: Mean 25(OH)D concentration was 13.4 (SD 9.7) ng/ml, which was significantly below the reference mean of 26.4 (SD 13.2) ng/ml (p<0.001). Vitamin D deficiency (25(OH)D concentration ≤8 ng/ml) was found in 38.1% of patients and was accompanied by raised concentrations of PTH and significantly increased markers of bone resorption (p<0.05). Low 25(OH)D concentrations correlated significantly with lower BMD z scores of the spine (r=0.38; p=0.02) and hip (r=0.33; p=0.04). Conclusions: We found reduced 25(OH)D concentrations in patients with small intestinal resection, and showed that a deficient 25(OH)D concentration is associated with significantly increased markers of bone resorption and decreased BMD values.

The colon in carbohydrate malabsorption : short-chain fatty acids, pH, and osmotic diarrhoea

Short-chain (C2-C6) fatty acids (SCFA) are the major anions in colonic contents and the result of anaerobic fermentation of mainly saccharides. The effects and regulation of saccharide fermentation were studied in vitro and in vivo. In vitro faecal incubation was used to study the effects of lactose, glucose, and galactose and of pH on SCFA formation. Changing the pH to below 5 or above 11 abolished SCFA formation in the faecal incubates; in the pH 5-9 interval SCFA production was high, with only minor pH dependence. Adding glucose, galactose, or lactose to the incubation system increased SCFA production, but at high saccharide concentrations (100-300 mmol/l) SCFA formation was inhibited by the pH change. In vivo disaccharide malabsorption with increasing doses of lactulose caused a decrease in faecal pH to less than 5, values inhibitory to fermentation, before the appearance of carbohydrate in faeces. In 6 of 12 volunteers diarrhoea occurred suddenly and was caused by malabsorbed non-fermented carbohydrate. The six other volunteers had a gradual increase in faecal output with lactulose dose and developed diarrhoea before the appearance of saccharide in faeces. The intake of lactulose tolerated before diarrhoea ensued varied between individuals, with the majority having diarrhoea of more than 11/day at 160 g lactulose per day. At this dose SCFA absorption was estimated to be in the range 550 to 1150 mmol/day.

Effect of high-dose growth hormone and glutamine on body composition, urine creatinine excretion, fatty acid absorption, and essential fatty acids status in short bowel patients : A randomized, double-blind, crossover, placebo-controlled study

BACKGROUNDnPositive effects of high dose growth hormone and glutamine (GH + GLN) on body composition in short bowel patients have been described. Lack of effects on intestinal absorption found in some studies has been ascribed to concomitant essential fatty acid (EFA) deficiency. This study describes changes in body weight (BW) and composition, 24-h urine creatinine excretion, intestinal fatty acid absorption (total, saturated, unsaturated and EFA), and EFA status in relation to treatment with GH + GLN in 8 short bowel patients.nnnMETHODSnA double-blind, crossover study between placebo and growth hormone (mean, 0.12 mg/kg/day) plus oral (mean, 28 g/day) and parenteral glutamine (mean, 5.2 g/day) for 28 days. Body composition was measured by dual-energy absorptiometry (DEXA) scans. Intestinal fatty acid absorption was evaluated in balance studies, and EFAs were measured in plasma phospholipids by gas liquid chromatography.nnnRESULTSnActive treatment did not increase BW, lean body mass (LBM), fat mass (FM) and bone mass significantly compared with placebo treatment, but BW increased 1.03 kg (1.7%, P < 0.05), LBM 2.93 kg (8.7%, P < 0.001) and FM decreased 2.41 kg (10.6%, P < 0.001) in comparison with baseline. Twenty-four-hour urine creatinine excretion did not differ between study periods. No changes in intestinal absorption of fatty acids were seen, and no changes in EFAs measured in plasma phospholipids were observed. Only 1 of 8 patients, who did not receive parenteral lipids, had a Holman index above 0.2, indicative of EFA deficiency. All developed peripheral oedema.nnnCONCLUSIONSnCombined high dose growth hormone and glutamine administered for 4 weeks, did not improve absorption of fatty acids or EFA status in short bowel patients. No changes in BW or composition were seen when comparing treatment to placebo periods. The increase in LBM measured by DEXA scan, comparing treatment and baseline periods, was not accompanied by an increase in the 24-h urinary creatinine excretion and is suspected to be associated with an accumulation in extracellular fluids.Background: Positive effects of high dose growth hormone and glutamine (GH + GLN) on body composition in short bowel patients have been described. Lack of effects on intestinal absorption found in some studies has been ascribed to concomitant essential fatty acid (EFA) deficiency. This study describes changes in body weight (BW) and composition, 24-h urine creatinine excretion, intestinal fatty acid absorption (total, saturated, unsaturated and EFA), and EFA status in relation to treatment with GH + GLN in 8 short bowel patients. Methods: A double-blind, crossover study between placebo and growth hormone (mean, 0.12 mg/kg/day) plus oral (mean, 28 g/day) and parenteral glutamine (mean, 5.2 g/day) for 28 days. Body composition was measured by dual-energy absorptiometry (DEXA) scans. Intestinal fatty acid absorption was evaluated in balance studies, and EFAs were measured in plasma phospholipids by gas liquid chromatography. Results: Active treatment did not increase BW, lean body mass (LBM), fat mass (FM) and bone mass significantly compared with placebo treatment, but BW increased 1.03 kg (1.7%, P < 0.05), LBM 2.93 kg (8.7%, P < 0.001) and FM decreased 2.41 kg (10.6%, P < 0.001) in comparison with baseline. Twenty-four-hour urine creatinine excretion did not differ between study periods. No changes in intestinal absorption of fatty acids were seen, and no changes in EFAs measured in plasma phospholipids were observed. Only 1 of 8 patients, who did not receive parenteral lipids, had a Holman index above 0.2, indicative of EFA deficiency. All developed peripheral oedema. Conclusions: Combined high dose growth hormone and glutamine administered for 4 weeks, did not improve absorption of fatty acids or EFA status in short bowel patients. No changes in BW or composition were seen when comparing treatment to placebo periods. The increase in LBM measured by DEXA scan, comparing treatment and baseline periods, was not accompanied by an increase in the 24-h urinary creatinine excretion and is suspected to be associated with an accumulation in extracellular fluids.