Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. METHODS: We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. RESULTS: TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. CONCLUSION: In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect.

[Retrograde jejunal intussusception after gastric bypass]. / Retrograd invagination af jejunum efter gastrisk bypass.

The preferred technique in Denmark for surgical intervention for morbid obesity is laparoscopic Roux-en-Y gastric bypass. A rare complication to gastric bypass is intussusception of the small intestines. However, this diagnosis is difficult to determine clinically and an acute computed tomography is often necessary. We present the first case of retrograde jejunal intussusception after gastric bypass in Scandinavia.

The effects of TNF-α on GLP-1-stimulated plasma glucose kinetics.

CONTEXT: Glucagon-like peptide-1 (GLP-1) analogs have recently been promoted as antihyperglycemic agents in critically ill patients with systemic inflammation, but the effects of TNF-α on glucose metabolism during GLP-1 administration are unknown. OBJECTIVE: The objective of the study was to determine whether the infusion of TNF-α at high physiological levels impairs GLP-1's effects on glucose metabolism. DESIGN: This was a randomized, controlled, cross-over trial. SETTING: The study was conducted at a hospital clinical research laboratory. PARTICIPANTS: Twelve healthy males (aged 24 ± 3 y; body mass index 22.9 ± 1.3 kg/m(2)). INTERVENTIONS: After an overnight fast, either saline (0.9%) or recombinant human TNF-α (1000 ng/m(2) · h) was infused from t = 0-6 hours. At t = 2 hours, GLP-1 infusion (0.5 pmol/kg · min) began. From t = 4-6 hours, the GLP-1 infusion rate was increased to 1.2 pmol/kg · min. Plasma glucose was clamped at 5 mmol/L throughout via a variable rate 20% dextrose infusion. Trials were 7-14 days apart. MAIN OUTCOME MEASURES: Endogenous glucose production (EGP) was measured by the [6,6-(2)H2]glucose isotope tracer dilution method. RESULTS: GLP-1 infusion suppressed plasma glucagon (P < .01), elevated plasma insulin, and C-peptide (P < .01) and suppressed EGP (P < .001) during the saline infusion. In contrast, the infusion of TNF-α increased plasma TNF-α and IL-6, elevated body temperature, and blunted the GLP-1-induced suppression of EGP during high-dose GLP-1 infusion (all P < .05, TNF-α vs saline). However, TNF-α infusion lowered plasma GLP-1 during high-dose GLP-1 infusion (P < .001). CONCLUSIONS: TNF-α induces systemic inflammation and reduces plasma GLP-1, thereby reducing the suppression of EGP during GLP-1 infusion. This may have clinical relevance if GLP-1 analog drugs are used for the treatment of hyperglycemia in critically ill patients.

Colonoscopy results are not enhanced by use of magnet endoguide in specialist practice.

INTRODUCTION: It is discussed whether the use of a magnetic positioning device (OLYMPUS; UPD (unit of magnetic positioning device)) enhances the success of the colonoscopic procedure. Concern for patient compliance and endoscopic efficiency has been voiced in connection with the implementation of colon cancer screening. UPD has been proposed as a tool for optimization of results and reduction of patient discomfort. In this study, we aimed to qualify the debate by examining the success rate and patient discomfort in an unselected colonoscopy population referred to specialist clinics with experienced investigators. Furthermore, the study assessed the effect of using a UPD. MATERIAL AND METHODS: A total of 1,068 consecutive patients referred for colonoscopy were enrolled and randomised for investigation with or without use of UPD. The evaluation endpoints were: success rate (coecum visualised, ileal intubation was carried out at the investigator's discretion), duration of procedure, and patient discomfort indicated by the patient as a visual analogue scale score. RESULTS: No significant differences between the two investigational procedures were demonstrated in relation to the chosen endpoints. CONCLUSION: UPD is convenient to have, but not a necessity for colonoscopy. FUNDING: The study was supported by the Danish Association of Medical Specialists. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency, journal no. 2009-41-3716, the National Ethics Committee, journal no.: H-1-2009-80, and registered with ClinicalTrials.gov., protocol no: NCT01055782.