The effects of laparoscopic Roux-en-Y gastric bypass and one-anastomosis gastric bypass on glycemic control and remission of type 2 diabetes mellitus: study protocol for a multi-center randomized controlled trial (the DIABAR-trial).

BACKGROUND: Metabolic surgery induces rapid remission of type 2 diabetes mellitus (T2DM). There is a paucity of high level evidence comparing the efficacy of the laparoscopic Roux-en-Y gastric bypass (RYGB) and the laparoscopic one-anastomosis gastric bypass (OAGB) in glycemic control. Also, the mechanisms that drive the conversion of T2DM in severe obese subjects to euglycemia are poorly understood. METHODS: The DIABAR-trial is an open, multi-center, randomized controlled clinical trial with 10 years follow-up which will be performed in 220 severely obese patients, diagnosed with T2DM and treated with glucose-lowering agents. Patients will be randomized in a 1:1 ratio to undergo RYGB or OAGB. The primary outcome is glycemic control at 12 months follow-up. Secondary outcome measures are diverse and include weight loss, surgical complications, psychologic status and quality of life, dietary behavior, gastrointestinal symptoms, repetitive bloodwork to identify changes over time, glucose tolerance and insulin sensitivity as measured by mixed meal tests, remission of T2DM, presence of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in liver biopsy, oral and fecal microbiome, cardiovascular performance, composition of bile acids, and the tendency to develop gallstones. DISCUSSION: The DIABAR-trial is one of the few randomized controlled trials primarily aimed to evaluate the glycemic response after the RYGB and OAGB in severe obese patients diagnosed with T2DM. Secondary aims of the trial are to contribute to a deeper understanding of the mechanisms that drive the remission of T2DM in severe obese patients by identification of microbial, immunological, and metabolic markers for metabolic response and to compare complications and side effects of RYGB and OAGB. TRIAL REGISTRATION: ClinicalTrials.gov NCT03330756 ; date first registered: October 13, 2017.

Hemodynamic response to LBNP following 2 hours HDT (-6 degrees).

Central hemodynamics have been determined during stepwise decreasing LBP in head-down tilt (HDT) of -6 degrees. Measurements were performed on eight healthy volunteers using right heart catheterization. During LBNP, pressures in the right atrium, pulmonary artery, and pulmonary capillary (preload) decreased in parallel with the increase of negative pressure applied to the lower part of the body. Similarly, stroke volume and cardiac output decreased with increasing negative pressure. Heart rate moderately increased (30%) as well as total peripheral resistance. The left ventricular function curve was shifted downward and to the left during LBNP indicating hypovolemia with no evidence of decreased contractility. Cardiac dimensions determined by echocardiography changed in a similar way as those obtained by invasive measurements. There was a very close correlation between stroke volume determined by thermodilution and by echocardiography. Plasma norepinephrine and dopamine tended to increase at the end of LBNP. Echocardiography proved a useful and reliable approach to hemodynamic measurement during LBNP and is recommended for analysis of hemodynamic parameters during zero G and Gz simulation.

Trophic effect of truncal vagotomy on the rat pancreas.

The trophic effect of truncal vagotomy was studied in rats. Three months after vagotomy and pyloroplasty pancreatic weight was significantly increased by 40% (p less than 0.001). Gastric stasis and consecutive distension of the stomach was observed in the majority of vagotomized animals despite pyloroplasty; the trophic effect of vagotomy on the pancreas was most pronounced in animals with severe stomach distension. Basal gastrin levels were increased after truncal vagotomy but did not correlate to gastric stasis and to the hypertrophy and hyperplasia of the exocrine pancreas. Basal pancreatic polypeptide hexapeptide levels were not altered after vagotomy. Morphometric studies on the endocrine pancreatic tissue showed that the relative volume density decreased due to the increase in exocrine tissue. However, the total islet cell mass remained constant. It is concluded that chronic truncal vagotomy has a trophic effect on the exocrine but not on the endocrine pancreas; additional factors besides gastrin seem to be responsible for this.

Central hemodynamics during zero gravity simulated by head-down bedrest.

Central hemodynamics during head-down tilt of -6 degrees lasting for 2 h were studied using catheterization of the pulmonary artery. M-mode echocardiography was performed simultaneously. Significant increases occurred for pressures in the right atrium, pulmonary artery in pulmonary wedge position, and for pulmonary vascular resistance. Cardiac and stroke volume index, heart rate, mean arterial pressure, and total systemic resistance remained constant throughout the exposure time. Constancy was also observed for echocardiographic measures of cardiac dimensions. It is concluded that head-down tilt leads to an increase of preload without any evidence of disturbed left ventricular function. No distinct time course of hemodynamic variables could be seen. Echocardiography proved a useful method to study cardiovascular adaptations during head-down tilting.

Pancreatic polypeptide response to sham feeding in man.

The relationship between gastric acid secretion and the release of pancreatic polypeptide (PP) during modified sham feeding was studied in 29 duodenal ulcer patients and 10 healthy controls. Ulcer patients showed higher basal plasma PP levels than age-matched controls (p less than 0.01). Acid secretion and PP levels were stimulated in the majority of patients and controls during sham feeding; however, no correlation was found between basal and vagally stimulated acid secretion and basal PP levels. Gastrin levels did not change in both groups. It is concluded from the present study that changes in plasma PP levels do not reflect sham feeding induced stimulation of the parietal cells.

[Testosteron treatment of excessively tall boys (author's transl)]. / Testosteron-Therapie hochwüchsiger Jungen. Ergebnisse bei 25 Jungen.

Twenty-five boys aged 11.7-16.8 years with constitutionally tall stature were treated with 500 mg testosteron oenanthate two-weekly over a period of 15.6 months on average. Prediction of height was done according to Bayley-Pinneau (BP) and Tanner et al. with a mean parent height of 168 cm (T168) and 172 cm (T172). It was on average at 202.73 cm (BP) and 203.26 cm (T168) or 201.97 (T172). The achieved height reduction was 7.2 cm (BP), 7.73 cm (T168) and 6.44 cm (T172), corresponding to a reduction of 45.6% (BP), 47.3% (T168) and 41% (T172) of the future growth. Whereas the major reductions were obtained in the youngest patients, success of treatment in patients with a skeletal age of 15 and more years was not demonstrable with certainty. Predominant side effects were weight gain within the first 6 months, acne and transient reduction of testicular volume.

A new application of LBNP to measure orthostatic tolerance before and after 0-g simulation (water immersion).

Lower body negative pressure (LBNP) remains an important device for the generation of orthostatic stress in the space flight environment as well as a tool to measure inflight and postflight changes in orthostatic response. These applied levels of LBNP have typically not exceeded 50-60 mm Hg negative pressure. Information is incomplete as to the levels of absolute LBNP orthostatic tolerance, and the factors responsible for their variance. A better definition of the tolerance limits for males and females could be expected to aid the evaluation of lower levels of LBNP. An LBNP device was built to study absolute orthostatic tolerance; additionally, another LBNP device was constructed to permit orthostatic tolerance testing directly after a controlled water immersion period. Absolute LBNP orthostatic tolerance patterns are analyzed for a group of males and females (series I). A preliminary statement on the variations of LBNP orthostatic tolerance after limited periods of water immersion and bed rest is also provided (series II).

[Gastric acid response to food in duodenal ulcer patients before and after selective proximal vagotomy (SPV) (author's transl)]. / Nahrungsstimulierte Säuresekretion bei Ulcus duodeni--Patienten vor und nach selektiv proximaler Vagotomie (SPV).

In duodenal ulcer patients the maximal acid secretion induced by pentagastrin is significantly higher than the meal-induced acid secretion (10% peptone, pH 5.5). Three months after SPV there is no difference in pentagastrin and meal-induced stimulation. There is a reduction of 56% in insulin-negative patients after SPV, but only of 9% in insulin-positive patients. Basal serum gastrin levels increased significantly after SPV, but there is no difference in postprandial serum gastrin levels and in insulin-positive and insulin-negative patients. Intragastric titration seems to be a subtle method for testing the completeness of SPV.

[Inhibition of gastric secretion by i.v. gastric inhibitory polypeptide (GIP) in man (author's transl)]. / Hemmung der Magensekretion durch intervenöses Gastric Inhibitory Polypeptid (GIP) beim Menschen.

Infusions of GIP in man with innervated stomach is only a potent inhibitor of gastric secretion in high pharmacological doses. Cholinergic mechanisms seem to have an influence on the inhibitory effect of GIP on gastric secretion.

Effect of vagotomy on gastrointestinal hormones.

Different types of vagotomy have been widely used in the treatment of peptic ulcer disease. A close relationship between the vagus nerve and the release or action of gastrointestinal hormones is necessary for the optimal activation of the gastrointestinal tract. The serum concentrations of the antral hormone gastrin are elevated after all types of vagotomy. The postvagotomy hypergastrinemia is due to the change in pH in the antral lumen or the gastric motility changes, both of which may lead to a proliferation of G cells. The reduction in pancreatic secretion after vagotomy is not due to changes in intestinal hormone release, but may be caused by the interruption of a postulated enteropancreatic reflex. Postprandial GIP release and serum insulin levels are not affected by vagotomy, but basal GIP levels are increased after vagotomy. Postprandial pancreatic polypeptide release is nearly abolished by vagotomy, but seems to normalize in the later postoperative course. These findings may be important for the interpretation of pathophysiologic changes after vagotomy.

[Release of pancreatic polypeptide (PP) or secretin after vagotomy (author's transl)]. / Freisetzung von "Pancreatic Polypeptide" (PP) und Sekretin nach Vagotomie.

The question has been risen whether "pancreatic polypeptide" (PP) determination is a suitable index for a successful vagotomy. Three months after truncal vagotomy (TV) there was only a slight postprandial increase of PP levels whereas five years after TV a normal PP response was found compared to controls. Vagal induced PP release was completely abolished after TV. Selective proximal vagotomy did not influence vagal and food stimulated PP release significantly. It can be concluded that PP determination does not prove to be a suitable index for a successful vagotomy.

[Treatment of hemorrhage from acute gastric and duodenal mucosa lesions with secretin]. / Die Behandlung der Blutung aus akuten Schleimhautläsionen des Magens und Duodenums durch Secretin.

In a prospective study 67 patients with bleeding from acute gastric mucosal lesions were treated by intravenous infusion of secretin. In 64 of the 67 patients bleeding stopped during secretin infusion. In 16 of these 64, bleeding recurred after cessation of the secretin infusion; all recurrences were stopped by secretin. Severe side effects were not observed. Secretin seems to be an effective drug in the treatment of stress ulcer bleeding.

[Glucose-homeostasis in resection and non-resection procedures of the stomach]. / Glucose-Homeostase bei resezierenden und nicht resezierenden Verfahren am Magen.

Antrectomy or truncal vagotomy with pyloroplasty induces an abnormal alimentary hyperglycemia after ingestion of oral glucose. Low doses of secretin normalize the glucose homeostasis in dogs after antrectomy and truncal vagotomy.

[The effect of selective proximal vagotomy on gastrin, GIP and insulin blood levels in patients with duodenal ulcer]. / Der Einfluss der selektiv-proximalen Vagotomie auf die Serumspiegel von Gastrin, GIP und Insulin bei Ulcus-duodeni-Patienten.

1. In duodenal ulcer patients SPV results in an increase of basal and postprandial serum gastrin levels. There is no decrease of hypergastrinemia even five years after SPV. 2. After SPV there is a significant increase in basal serum GIP levels; postprandial GIP concentrations show a faster increase after food intake. 3. Serum insulin and blood glucose concentrations are not altered by SPV.

Serum gastric inhibitory polypeptide (GIP) in duodenal ulcer disease: relationship to glucose tolerance, insulin, and gastrin release.

Serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG), and insulin (IRI) were estimated in 41 normal weight patients with duodenal ulcer (DU) and 25 age-matched controls in response to a high calorie liquid test meal. 28 out of 41 DU patients had a hyperglycaemic glucose response during the test meal, and 15 had a pathological oral glucose tolerance test. Fasting and food-stimulated IR-GIP and IRG levels were significantly elevated in the DU patients. Serum IRI also increased to significantly higher levels in DU patients after the test meal. The degree of the greater hormone response was dependent on the glucose increase after the test meal in the case of insulin and GIP, but not in the case of gastrin. It is concluded: firstly, that a faster glucose absorption (possibly due to rapid initial gastric emptying or increased intestinal motility) is responsible for the high and short-lasting glucose peak and the increased GIP and insulin secretion; secondly, that the GIP response could well be causally related to the insulin response; thirdly, that hyposcretion of GIP is ruled out as a possible factor in the pathogenesis of gastric acid hypersecretion of duodenal ulcer patients.

[The effect of antrectomy or total gastrectomy on calcium-induced gastrin secretion and gastrin release in man (author's transl)]. / Der Einfluss der Antrektomie oder der totalen Gastrektomie auf die calciuminduzierte Magensekretion und die Gastrinfreisetzung beim Menschen.

The effect of induced hypercalcemia on serum gastrin concentrations, measured by radioimmunoassay, and gastric acid secretion was studied in 20 healthy subjects, 8 patients after antrectomy and gastroduodenostomy (Billroth I), 12 patients after antrectomy and gastrojejunostomy (Billroth II) and in 9 patients after total gastrectomy and esophagojejunostomy. In normal man calcium stimulates gastric secretion and gastrin release. After antrectomy gastric secretion is still stimulated by calcium without changing serum gastrin levels. After total gastrectomy basal serum gastrin concentration is further reduced; calcium does not liberate gastrin. These results show that calcium-induced gastric secretion is caused by direct action at the parietal cell level besides the gastrin release from the antrum. In man, extra antral gastrin cannot be released by induced hypercalcemia.

[Gastrointestinal hormone release in dumping symdrome before and after reconstruction of duodenal passage]. / Die Freisetzung gastrointestinaler Hormone beim Dumping-Syndrom vor und nach Wiederherstellung der Duodenalpassage.

Serum gastrin, serum-GIP and serum insulin levels were measured before and after interposition operation (Henley-Soupault) in 10 patients with severe dumping-syndrome (PGS). The results were compared to those obtained in 10 normal subjects without any gastrointestinal disease. In the PGS pre-operative group there was a significantly lower serum gastrin concentration compared to normals, while the serum-GIP-concentration was significantly higher. After interposition operation all serum-hormone-levels tended towards normal values. There was no difference between the basal serum insulin levels of the three groups. The change in postprandial insulin release was parallel to the serum-GIP-levels. It is concluded that there is a close connection between disturbed release of gastrointestinal hormones and the dumping syndrome.