Andrea Karen Floyd

Preoperative β‐cell function in patients with type 2 diabetes is important for the outcome of Roux‐en‐Y gastric bypass surgery

Roux‐en‐Y gastric bypass surgery leads to remission of type 2 diabetes in the majority of patients suffering from the disease. The gut hormone glucagon‐like peptide‐1 is believed to be of major importance for the remission process. The present project demonstrates a marked difference in the chance of remission of type 2 diabetes in patients with low or high preoperative β‐cell function in spite of a similar post‐surgery increase in postprandial glucagon‐like peptide‐1 release. Furthermore, post‐surgery intravenous glucose administration, which does not stimulate release of glucagon‐like peptide‐1, leads to increased insulin secretion in the patients with the best preoperative β‐cell function. Together the present findings indicate that patients with type 2 diabetes with high preoperative β‐cell function experience a glucagon‐like peptide‐1‐independent increase in β‐cell function after gastric bypass surgery.

Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma

Low-abundance regulatory peptides, including metabolically important gut hormones, have shown promising therapeutic potential. Here, we present a streamlined mass spectrometry-based platform for identifying and characterizing low-abundance regulatory peptides in humans. We demonstrate the clinical applicability of this platform by studying a hitherto neglected glucose- and appetite-regulating gut hormone, namely, oxyntomodulin. Our results show that the secretion of oxyntomodulin in patients with type 2 diabetes is significantly impaired, and that its level is increased by more than 10-fold after gastric bypass surgery. Furthermore, we report that oxyntomodulin is co-distributed and co-secreted with the insulin-stimulating and appetite-regulating gut hormone glucagon-like peptide-1 (GLP-1), is inactivated by the same protease (dipeptidyl peptidase-4) as GLP-1 and acts through its receptor. Thus, oxyntomodulin may participate with GLP-1 in the regulation of glucose metabolism and appetite in humans. In conclusion, this mass spectrometry-based platform is a powerful resource for identifying and characterizing metabolically active low-abundance peptides.

Roux-en-Y gastric bypass alleviates hypertension and is associated with an increase in mid-regional pro-atrial natriuretic peptide in morbid obese patients.

Objective: To examine 24-h blood pressure (24BP), systemic haemodynamics and the effect of sodium intake on 24BP in obese patients before and after gastric bypass surgery [laparoscopic Roux-en-Y gastric bypass (LRYGB)], and to determine whether weight loss from LRYGB might be related to an increase in plasma concentrations of atrial natriuretic peptide. Methods: Twelve hypertensive and 12 normotensive morbidly obese patients underwent LRYGB: 24BP, systemic haemodynamics and mid-regional pro-atrial natriuretic peptide (MRproANP) were assessed before, 6 weeks and 12 months after surgery. The effect of high versus low sodium intake on 24BP was evaluated before and 12 months after LRYGB. Results: Six weeks after LRYGB, the average weight loss was 20 kg, with a further 21 kg weight loss 1 year after surgery. In hypertensive patients, 24BP was significantly reduced at 6 weeks, but not 1 year after LRYGB. However, antihypertensive medications were successively reduced from baseline to 1 year after surgery. In normotensive patients, there was no change in 24BP 6 weeks after LRYGB, but a tendency towards a reduction 1 year after the operation. Plasma concentrations of MRproANP were subnormal prior to surgery in hypertensive patients and increased by 77% 1 year after the operation. In normotensive patients, preoperative concentrations were normal and increased only by 6%. High sodium intake induced plasma volume expansion, increased stroke volume and cardiac output, but no significant change in 24BP – neither before nor after LRYGB. Conclusions: LRYGB resulted in a significant 24BP reduction and a substantial increase in MRproANP plasma concentrations in hypertensive, obese patients 6 weeks after surgery, suggesting a causal link between obesity–hypertension and altered release/degradation of cardiac natriuretic peptides.

Hepatic mitochondrial oxidative phosphorylation is normal in obese patients with and without type 2 diabetes

Hepatic insulin resistance in patients with obesity or type 2 diabetes has been suggested to result from hepatic mitochondrial dysfunction. High‐resolution respirometry (HRR) can be used to assess oxidative phosphorylation by measuring the mitochondrial oxygen consumption rate in the individual complexes of the mitochondria. By using HRR, the present study demonstrates no difference in hepatic mitochondrial oxidative phosphorylation among subjects with obesity with or without type 2 diabetes and non‐obese controls. Furthermore, the amount of mitochondria, assessed by the citrate synthase activity, is not different between the three groups. Together the present findings indicate that hepatic mitochondrial oxidative phosphorylation capacity is not impaired in patients with obesity or type 2 diabetes.

Internal herniation after laparoscopic antecolic Roux-en-Y gastric bypass: a nationwide Danish study based on the Danish National Patient Register.

BACKGROUND Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most common surgical treatment for morbid obesity in Denmark. Internal herniation (IH) or intermittent internal herniation (IIH) is a major late complication after LRYGB due to persistent mesenteric defects. However, the incidence of IH/IIH is still not known in Denmark. OBJECTIVES The primary aim of the study was to assess the incidence of IH/IIH after LRYGB performed in the period between 2006 and 2011 with a follow-up until 2013, where mesenteric defects were not routinely closed during the primary operation. SETTING Department of Bariatric Surgery, Koege University Hospital, Denmark METHODS We performed a retrospective nationwide analysis of prospectively collected data from all patients with LRYGB performed in Denmark from 2006 to 2011 based on the Danish National Patient Registry (NPR). From January 2006 to December 2011, 12,221 patients underwent an LRYGB procedure in Denmark. Relevant data from all 12,221 patients were retrieved from the NPR during the follow-up period from January 2006 to May 2013; we registered possible subsequent abdominal operations in these patients. RESULTS Operations were performed on 398 patients because of suspected IH/IIH; 383 of these patients had IH/IIH (3.1%; 95% CI 2.8-3.5). The estimate for the 5-year cumulative incidence of clinically significant cases with IH/IIH was 4%. The median time interval until the onset of IH/IIH after LRYGB was 15 months (range 0-67 months) in a follow-up period with a median of 38 months (range 16-87 months). CONCLUSION In the period from 2006 to 2011, mesenteric defects were not routinely closed during LRYGB in Denmark. The cumulative 5-year incidence of IH/IIH after LRYGB was 4% in a median follow-up period of 38 months (range 16-87) in Denmark when data was retrieved from the NPR.

The influence of high versus low sodium intake on blood pressure and haemodynamics in patients with morbid obesity.

Background: Many patients with morbid obesity (BMI > 40 kg/m2) have hypertension. The complex pathophysiological abnormalities linking hypertension to obesity have not been fully clarified, but abnormal sodium handling could be an important mechanism. Method: Therefore, we examined changes in body fluid compartments and haemodynamic responses (at rest and during exercise) after 5 days of a low-sodium diet (90 mmol/day) and 5 days of a high-sodium diet (250 mmol/day) in 12 morbidly obese, hypertensive patients; 12 morbidly obese, normotensive patients and 12 nonobese controls. Results: High sodium intake as compared to low sodium intake was associated with an increase in plasma volume (obese, hypertensive patients: 5 ± 4%; obese, normotensive patients: 10 ± 11%; nonobese controls: 7 ± 6%), cardiac output (CO) (obese, hypertensive patients: 17 ± 12%; obese, normotensive patients: 20 ± 16%; nonobese controls: 13 ± 14%) and stroke volume (SV) (obese, hypertensive patients: 27 ± 26%; obese, normotensive patients: 27 ± 24%; nonobese controls: 18 ± 27%) in all three groups with no differences between the groups. Despite an increase in CO during high salt intake, 24-h blood pressure (BP) was unchanged in patients and controls as a result of a reduction in total peripheral resistance (obese, hypertensive patients: −11 ± 11%; obese, normotensive patients: −10 ± 12%; nonobese controls: −5 ± 14%). Similar changes were observed during an incremental bicycle exercise test wherein CO and SV were higher, whereas mean arterial BP was unchanged at each exercise level during high sodium intake. Conclusion: Despite substantial increases in CO and SV, we did not observe any significant change in BP during high sodium intake, neither in morbid obese patients nor in lean individuals.

Mitochondrial respiratory capacity remains stable despite a comprehensive and sustained increase in insulin sensitivity in obese patients undergoing gastric bypass surgery

It has been proposed, but not yet demonstrated by convincing evidence in published articles, that insulin resistance and mitochondrial respiratory function are causally related physiological phenomena. Here, we tested the prediction that weight loss–induced increase in insulin sensitivity will correlate with a corresponding change in mitochondrial respiratory capacity over the same time period.

Comment on: Does the closure of mesenteric defects during laparoscopic gastric bypass surgery cause complications?

Abstract Background A well-known complication of laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) is bowel obstruction due to internal herniation (IH). Evidence suggests that mesenteric defects should be closed during LRYGB to reduce the risk of IH. Therefore, surgeons are now closing mesenteric defects during LRYGB using sutures, clips, or fibrin glue. However, it has been reported that complications may arise due to the closure of mesenteric defects. The aim of this review was to summarize the reported possible complications associated with the closure of mesenteric defects during LRYGB. Methods A literature search of PubMed and EMBASE was performed to identify studies related to the closure of mesenteric defects during LRYGB. The studies were screened for the listing of possible complications associated with the closure of mesenteric defects. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. Results Thirty studies complied with the inclusion criteria for our analysis, which included 21,789 patients. Reported complications related to closure of the mesenteric defects were: small bowel obstruction because of IH, kinking, and adhesions. IH occurred because of incomplete closure of the mesenteric defects in 1.4% of all patients, 1.2% by the antecolic approach, and 1.9% by the retrocolic approach, respectively. Kinking of the small bowel occurred in .2% of 1630 patients after closure of the mesenteric defects with clips and adhesion formation was found among 4.6% of 152 patients after closure of the mesenteric defects with nonabsorbable sutures. Conclusions The reported risk of complications caused by closure of the mesenteric defects during LRYGB seems low.

Patient profiling for success after weight loss surgery (GO Bypass study): An interdisciplinary study protocol

Despite substantial research efforts, the mechanisms proposed to explain weight loss after gastric bypass (RYGB) and sleeve gastrectomy (SL) do not explain the large individual variation seen after these treatments. A complex set of factors are involved in the onset and development of obesity and these may also be relevant for the understanding of why success with treatments vary considerably between individuals. This calls for explanatory models that take into account not only biological determinants but also behavioral, affective and contextual factors. In this prospective study, we recruited 47 women and 8 men, aged 25–56 years old, with a BMI of 45.8 ± 7.1 kg/m2 from the waiting list for RYGB and SL at Køge hospital, Denmark. Pre-surgery and 1.5, 6 and 18 months after surgery we assessed various endpoints spanning multiple domains. Endpoints were selected on basis of previous studies and include: physiological measures: anthropometrics, vital signs, biochemical measures and appetite hormones, genetics, gut microbiota, appetite sensation, food and taste preferences, neural sensitivity, sensory perception and movement behaviors; psychological measures: general psychiatric symptom-load, depression, eating disorders, ADHD, personality disorder, impulsivity, emotion regulation, attachment pattern, general self-efficacy, alexithymia, internalization of weight bias, addiction, quality of life and trauma; and sociological and anthropological measures: sociodemographic measures, eating behavior, weight control practices and psycho-social factors. Joining these many endpoints and methodologies from different scientific disciplines and creating a multi-dimensional predictive model has not previously been attempted. Data on the primary endpoint are expected to be published in 2018. Trial registration Clinicaltrials. gov ID NCT02070081.

Reoperation risk following the first operation for internal herniation in patients with laparoscopic Roux‐en‐Y gastric bypass

Laparoscopic Roux‐en‐Y gastric bypass (LRYGB) is the most commonly used surgical procedure in the treatment of morbid obesity in Denmark. Internal herniation (IH) and intermittent internal herniation (IIH) are probably the most common late complications in patients with LRYGB. The aim of this study was to investigate a possible increased risk of subsequent operations after an initial IH or IIH event.