Ida B. Gottschalck

Home parenteral nutrition in Denmark in the period from 1996 to 2001.

Objective. Home parenteral nutrition (HPN) has been provided to patients with intestinal failure in Denmark since 1970. The results of a national survey comprising a well-defined cohort receiving treatment with HPN in Denmark in the period from 1996 to the end of 2000 are presented, including data on incidence, prevalence, patient characteristics and complications of HPN treatment. Material and methods. HPN was given to 202 patients (115 F, 87 M) 34% with short-bowel syndrome due to inflammatory bowel disease, 26% with cancer, 22% with surgical complications and 19% with other causes, for a total of 410 catheter years. Results. At the end of 2000, the prevalence of HPN in Denmark was 19.2 per million, and the average annual incidence was 5.0 per million per year over the 5-year period. The incidence rates of catheter-related bacteraemia and thrombosis were 0.48 and 0.02 episodes per catheter year, respectively. The average catheter lasted 1.5 years. Venous inaccessibility was never encountered. The 5-year mortality was 25% (n=51). However, only six deaths were related to HPN. Three patients died of HPN-related liver failure, two died of catheter-related sepsis and one patient died of an embolus induced by a catheter thrombus. Conclusions. Since its introduction in 1970 in Denmark, HPN has evolved from an experimental approach to a standardized therapy for patients with intestinal failure. Although HPN morbidity is increasing slightly compared with that reported in earlier surveys, HPN-induced mortality is still less than 1% per year.

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.

Short bowel patients treated for two years with glucagon-like peptide 2 (GLP-2): compliance, safety, and effects on quality of life.

Background and aims. Glucagon-like peptide 2 (GLP-2) has been shown to improve intestinal absorption in short bowel syndrome (SBS) patients in a short-term study. This study describes safety, compliance, and changes in quality of life in 11 SBS patients at baseline, week 13, 26, and 52 during two years of subcutaneous GLP-2 treatment, 400 microgram TID, intermitted by an 8-week washout period. Methods. Safety and compliance was evaluated during the admissions. The Sickness Impact Profile (SIP), Short Form 36 (SF 36), and Inflammatory Bowel Disease Questionnaire (IBDQ) evaluated quality of life. Results. The predominant adverse event was transient abdominal discomfort in 5 of 11 patients, but in 2, both suffering from Crohns disease, it progressed to abdominal pain and led to discontinuation of GLP-2 treatment. One had a fibrostenotic lesion electively resected at the jejuno-ascendo-anastomosis. The investigator excluded a patient due to unreliable feedback. Stoma nipple enlargement was seen in all 9 jejunostomy patients. Reported GLP-2 compliance was excellent (>93%). GLP-2 improved the overall quality of life VAS-score (4.1 ± 2.8 cm versus 6.0 ± 2.4 cm, P < .01), the overall SIP score (10.3 ± 8.9% versus 6.2 ± 9.5%, P < .001), the mental component of the SF-36 (45 ± 13% versus 53 ± 11%, P < .05), and the overall IBDQ score (5.1 ± 0.9 versus 5.4 ± 0.9, P < .007) in the 8 patients completing the study. Conclusions. Long-term treatment with GLP-2 is feasible in SBS patients, although caution must be exercised in patients with a history of abdominal pain. Although conclusions cannot be made in a noncontrolled trial, the high reported compliance might reflect a high treatment satisfaction, where the clinical benefits of GLP-2 may outweigh the discomforts of injections.

Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and short-bowel syndrome

Objective. The gut hormone GLP-2 (glucagon-like peptide-2) seems to be involved in the circadian pattern of bone resorption, whereas parathyroid hormone (PTH) is an established key hormone in bone turnover. Endogenous GLP-2 secretion is lacking in colectomized patients with short-bowel syndrome (SBS) and they have reduced bone mineral density (BMD). The aim of the study was to investigate the anti-resorptive effect (assessed by s-CTX) of 14 days of GLP-2 treatment in these patients and to determine whether 56 days of treatment would improve BMD. PTH secretion in response to GLP-2 was also investigated in colectomized SBS patients and colectomized controls (with ileostomy). Material and methods. Eight SBS patients and 13 patients with ileostomy were treated with subcutaneous injections of 1600 µg GLP-2 at bedtime for 56 and 14 consecutive days, respectively. BMD was determined at days 1 and 56 in SBS patients. On days 1 and 14, measurements of CTX, P1NP and PTH were taken 4 h after the GLP-2 injection. Results. Patients with ileostomy showed a significant reduction in bone resorption after GLP-2 injections at days 1 and 14. In contrast, there was no change in s-CTX after 1 and 14 days in the SBS patients, and after 56 days of GLP-2 treatment there was no improvement in BMD. A significant reduction in PTH secretion in response to GLP-2 was observed only in patients with ileostomy. Conclusions. The decreased bone resorption in response to GLP-2 injections cannot be elicited in SBS patients and therefore precludes treatment of their osteopenia with GLP-2. The anti-resorptive response to GLP-2 seems to require an intact small intestine and may involve suppression of PTH secretion.

Bone resorption is decreased postprandially by intestinal factors and glucagon-like peptide-2 is a possible candidate

Objective. Food intake inhibits bone resorption by a mechanism thought to involve gut hormones, and the intestinotrophic glucagon-like peptide 2 (GLP-2) is a candidate because exogenous GLP-2 inhibits bone resorption in humans. The purpose of the study was to investigate patients with short-bowel syndrome (SBS) or total gastrectomy in order to elucidate whether the signal for the meal-induced reduction of bone resorption is initiated from the stomach or the intestine. Material and methods. Bone resorption was assessed from the serum concentration of collagen type I C-telopeptide cross-links (s-CTX) and compared with the plasma concentrations of GLP-2. Bone formation was assessed from serum osteocalcin concentrations. Seven SBS patients with a preserved colon and 7 with SBS and colectomy and 7 healthy controls were given a breakfast test meal (936 kcal). Eight patients who had undergone total gastrectomy had an oral glucose load (75 g in 150 ml). Results. The SBS patients without a colon showed no reduction in bone resorption (s-CTX) to a meal, whereas SBS patients with a colon had an intermediate response with a 27% (p<0.05) reduction of s-CTX from baseline after 120 min as compared with 66% (p<0.001) for normal controls. A significant reduction of 53% (p<0.001) was seen in gastrectomized patients after receiving oral glucose, which is comparable with the published data for the oral glucose tolerance test (OGGT) in healthy subjects (50% reduction over 120 min). Bone formation was unchanged for both SBS and gastrectomy patients. GLP-2 concentrations increased significantly in all groups with the exception of the SBS plus colectomy group. Conclusions. An intestinal factor is responsible for the postprandial reduction in bone resorption, and our findings are compatible with such a function for GLP-2.

Reduction in bone resorption by exogenous glucagon-like peptide-2 administration requires an intact gastrointestinal tract

Objective. Biochemical markers for bone resorption (s-CTX) are reduced by food intake, whereas markers for bone formation seem to be unaffected by meal status. Glucagon-like peptide-2 (GLP-2) is a peptide secreted from endocrine L cells in the intestinal mucosa in relation to food-intake. Subcutaneous GLP-2 treatment has been shown to reduce bone resorption in postmenopausal women. The objective of this study was to investigate the ability of exogenous GLP-2 to reduce bone resorption in patients with jejunostomy or ileostomy and to elucidate whether an intact gastrointestinal tract and the ability to secrete GLP-2 are required for meal-induced inhibition of bone resorption. Material and methods. Fifteen control subjects, 13 colectomized patients with an ileostomy and 12 colectomized patients with a jejunostomy (remnant small bowel 89±53 cm) were given: a) a subcutaneous injection of 1600 µg GLP-2, b) placebo and c) 3.8 MJ of a breakfast meal. Blood was sampled for measurements of s-CTX, s-osteocalcin and GLP-2 for 4 h after each intervention. Results. After the GLP-2 injection, only control subjects showed a significant reduction in s-CTX (24%±13%, p=0.05, 120 min) compared with baseline values. Patients with an ileostomy had a preserved endogenous postprandial GLP-2 secretion, which was absent in patients with a jejunostomy. Consumption of a meal reduced s-CTX in all groups but significantly less so in the jejunostomy group. Conclusions. Reductions in bone resorption by exogenous GLP-2 require an intact gastrointestinal tract. The decreased meal-induced inhibition of bone resorption in the jejunostomy patients, who lack a GLP-2 response, supports the view that GLP-2 plays a role in postprandial reduction in bone resorption.

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

BACKGROUND Patients with Crohns disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination. METHODS In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS PCV13 induced a significantly higher antibody response for one serotype (23F) in IS treated patients and for two serotypes (9V and 23F) in untreated patients compared to CD patients vaccinated with PPV23. Untreated PPV23 recipients had higher responses for serotypes 9V and 18C compared to IS+TNF-α treated PPV23 recipients. Comparison between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response. CONCLUSION PCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD patients treated with immunosuppressive drugs alone or in combination with TNF-α antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments. The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).