Comparative impact of Roux-en-Y gastric bypass, sleeve gastrectomy or diet alone on beta-cell function in insulin-treated type 2 diabetes patients.

Although bariatric surgery is an effective treatment for type 2 diabetes by inducing weight loss and augmenting gut hormone secretion, the immediate effect on beta-cell function itself remains to be elucidated in type 2 diabetes. Therefore, a prospective, randomized trial was performed in 30 patients with insulin-treated type 2 diabetes and a body mass index ≥ 35 kg/m2. Patients were randomly assigned (1:1:1) to Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in combination with protein-sparing modified fast (PSMF), or to PSMF alone. Eu- and hyperglycemic clamps were performed before and 3 weeks after surgery and/or PSMF initiation. The primary outcome was the evolution of insulin sensitivity and beta-cell function after surgery, calculated using the composite measures of glucose disposal rate, insulin secretion rate, and disposition index (DI). Results revealed that markers of insulin sensitivity increased similarly in all arms (p = 0.43). A higher marker for maximal beta-cell function was observed when comparing SG to PSMF (p = 0.007). The DI showed a clear positive evolution after RYGB and SG, but not after PSMF alone. Altogether, these findings indicate that bariatric surgery results in an immediate beta-cell function recovery in insulin-treated type 2 diabetes.

Adipose tissue macrophage dysfunction is associated with a breach of vascular integrity in NASH.

BACKGROUND & AIMS: In non-alcoholic fatty liver disease (NAFLD), monocytes infiltrate visceral adipose tissue promoting local and hepatic inflammation. However, it remains unclear what drives inflammation and how the immune landscape in adipose tissue differs across the NAFLD severity spectrum. We aimed to assess adipose tissue macrophage (ATM) heterogeneity in a NAFLD cohort. METHODS: Visceral adipose tissue macrophages from lean and obese patients, stratified by NAFLD phenotypes, underwent single-cell RNA sequencing. Adipose tissue vascular integrity and breaching was assessed on a protein level via immunohistochemistry and immunofluorescence to determine targets of interest. RESULTS: We discovered multiple ATM populations, including resident vasculature-associated macrophages (ResVAMs) and distinct metabolically active macrophages (MMacs). Using trajectory analysis, we show that ResVAMs and MMacs are replenished by a common transitional macrophage (TransMac) subtype and that, during NASH, MMacs are not effectively replenished by TransMac precursors. We postulate an accessory role for MMacs and ResVAMs in protecting the adipose tissue vascular barrier, since they both interact with endothelial cells and localize around the vasculature. However, across the NAFLD severity spectrum, alterations occur in these subsets that parallel an adipose tissue vasculature breach characterized by albumin extravasation into the perivascular tissue. CONCLUSIONS: NAFLD-related macrophage dysfunction coincides with a loss of adipose tissue vascular integrity, providing a plausible mechanism by which tissue inflammation is perpetuated in adipose tissue and downstream in the liver. IMPACT AND IMPLICATIONS: Our study describes for the first time the myeloid cell landscape in human visceral adipose tissue at single-cell level within a cohort of well-characterized patients with non-alcoholic fatty liver disease. We report unique non-alcoholic steatohepatitis-specific transcriptional changes within metabolically active macrophages (MMacs) and resident vasculature-associated macrophages (ResVAMs) and we demonstrate their spatial location surrounding the vasculature. These dysfunctional transcriptional macrophage states coincided with the loss of adipose tissue vascular integrity, providing a plausible mechanism by which tissue inflammation is perpetuated in adipose tissue and downstream in the liver. Our study provides a theoretical basis for new therapeutic strategies to be directed towards reinstating the endogenous metabolic, homeostatic and cytoprotective functions of ResVAMs and MMacs, including their role in protecting vascular integrity.

SCFAs switch stem cell fate through HDAC inhibition to improve barrier integrity in 3D intestinal organoids from patients with obesity.

Stem cells are a keystone of intestinal homeostasis, but their function could be shifted during energy imbalance or by crosstalk with microbial metabolites in the stem cell niche. This study reports the effect of obesity and microbiota-derived short-chain fatty acids (SCFAs) on intestinal stem cell (ISC) fate in human crypt-derived intestinal organoids (enteroids). ISC fate decision was impaired in obesity, resulting in smaller enteroids with less outward protruding crypts. Our key finding is that SCFAs switch ISC commitment to the absorptive enterocytes, resulting in reduced intestinal permeability in obese enteroids. Mechanistically, SCFAs act as HDAC inhibitors in stem cells to enhance Notch signaling, resulting in transcriptional activation of the Notch target gene HES1 to promote enterocyte differentiation. In summary, targeted reprogramming of ISC fate, using HDAC inhibitors, may represent a potential, robust therapeutic strategy to improve gut integrity in obesity.

Personalized remotely guided preventive exercise therapy for a healthy heart (PRIORITY): protocol for an assessor-blinded, multicenter randomized controlled trial.

Aims: A key treatment for patients with varying stages of heart failure with preserved ejection fraction (HFpEF) is exercise. Yet, despite a Class 1A recommendation, only one-third of patients exercise sufficiently. A huge treatment gap exists between guidelines and clinical practice. PRIORITY aims to establish the feasibility, clinical effectiveness and cost-effectiveness of a hybrid centre and home-based personalized exercise and physical activity intervention for patients along the HFpEF continuum. Methods: An assessor-blinded, multicenter randomized controlled trial will be conducted among 312 patients along the HFpEF continuum. Participants will be randomized (1:1) to the PRIORITY intervention or a comparator group receiving only a written exercise prescription. Participants in the PRIORITY group will receive 18 supervised centre-based exercise sessions during one year, supplemented with a remotely guided home-based physical activity program. Outcomes will be assessed at baseline, 4 months, one and two years. The primary outcome is the peak oxygen uptake (pVO2) at 1-year. Secondary outcomes include physical activity, other physical fitness parameters, cardiovascular health, echocardiographic parameters, health-related quality of life and costs at 1-year FU. Machine learning algorithms will analyse big data on physical activity collected during the 1-year intervention to develop models that can predict physical activity uptake and adherence as well as changes in fitness and health. A cost-utility analysis will be performed to evaluate the cost-effectiveness of the PRIORITY intervention compared to the control condition. Discussion: We anticipate that participants in the supervised home-based exercise intervention group will have a greater increase in pVO2 compared to those receiving a written exercise prescription. Trial registration number: This trial is registered at ClinicalTrials.gov (NCT04745013) and is currently in the recruitment stage.

Change in carbohydrate intake one year after Roux-en-Y gastric bypass: A prospective study.

Background and objectives: To investigate the effect of carbohydrate intake before laparoscopic Roux-en-Y gastric bypass (LRYGB) on body weight, body composition and glycaemic status after surgery. Methods: In a tertiary centre cohort study, dietary habits, body composition and glycaemic status were evaluated before and 3, 6 and 12 months after LRYGB. Detailed dietary food records were processed by specialized dietitians on the basis of a standard protocol. The study population was subdivided according to relative carbohydrate intake before surgery. Results: Before surgery, 30 patients had a moderate relative carbohydrate intake (26%-45%, M-CHO), a mean body mass index (BMI) of 40.4 ± 3.9 kg/m² and a mean glycated haemoglobin A1c (A1C) of 6.5 ± 1.2% compared to 20 patients with a high relative carbohydrate intake (> 45%, H-CHO), mean BMI of 40.9 ± 3.7 kg/m² (non-significant, NS) and a mean A1C of 6.2% (NS). One year after surgery, body weight, body composition and glycaemic status were similar in the M-CHO (n = 25) and H-CHO groups (n = 16), despite less caloric intake in the H-CHO group (1317 ± 285 g vs. 1646 ± 345 g in M-CHO, p < 0.01). Their relative carbohydrate intake converged to 46% in both groups, but the H-CHO group reduced the absolute total carbohydrate consumption more than the M-CHO group (190 ± 50 g in M-CHO vs. 153 ± 39 g in H-CHO, p < 0.05), and this was especially pronounced for the mono- and disaccharides (86 ± 30 g in M-CHO vs. 65 ± 27 g in H-CHO, p < 0.05). Conclusion: A high relative carbohydrate intake before LRYGB, did not influence the change in body composition or diabetes status after surgery, despite a significantly lower total energy intake and less mono- and disaccharide consumption after surgery.

Effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal physiology.

BACKGROUND: Knowledge regarding the gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass is urgently needed to understand, prevent and treat the nutritional and pharmacological complications of bariatric surgery. AIM: To investigate the effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal motility (e.g., transit and pressure), pH, and intestinal bile acid concentration. MATERIAL AND METHODS: An exploratory cross-sectional study was performed in six participants living with obesity, six participants who underwent sleeve gastrectomy, and six participants who underwent Roux-en-Y gastric bypass. During the first visit, a wireless motility capsule (SmartPill©) was ingested after an overnight fast to measure gastrointestinal transit, pH, and pressure. During the second visit, a gastric emptying scintigraphy test of a nutritional drink labeled with 99mTc-colloid by a dual-head SPECT gamma camera was performed to measure gastric emptying half-time (GET1/2). During the third visit, two customized multiple lumen aspiration catheters were positioned to collect fasting and postprandial intestinal fluids to measure bile acid concentration. RESULTS: Immediate pouch emptying (P = 0.0007) and a trend for faster GET1/2 (P = 0.09) were observed in both bariatric groups. There was a tendency for a shorter orocecal transit in participants with sleeve gastrectomy and Roux-en-Y gastric bypass (P = 0.08). The orocecal segment was characterized by a higher 25th percentile pH (P = 0.004) and a trend for a higher median pH in both bariatric groups (P = 0.07). Fasting total bile acid concentration was 7.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) and 3.5-fold higher in the jejunum after sleeve gastrectomy (P = 0.009) compared to obesity. Postprandial bile acid concentration was 3-fold higher in the jejunum after sleeve gastrectomy (P = 0.0004) and 6.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) compared to obesity. CONCLUSION: The anatomical alterations of sleeve gastrectomy and Roux-en-Y gastric bypass have an important impact on gastrointestinal physiology. This data confirms changes in transit and pH and provides the first evidence for altered intraluminal bile acid concentration.

Patients with a History of Bariatric Surgery Are 8 Years Younger at Presentation with Severe Alcoholic Hepatitis.

PURPOSE: Patients with prior bariatric surgery (BS) are at risk to develop alcohol use disorder (AUD) and alcohol-related liver disease (ALD). Severe alcoholic hepatitis (sAH) is one of the most severe manifestations of ALD with a 28-day mortality of 20-50%. The impact of prior BS on patients presenting with sAH was assessed. METHODS: From 01/2008 to 04/2021, consecutive patients admitted to a tertiary referral center with biopsy-proven sAH were included in a database. RESULTS: One hundred fifty-eight sAH patients of which 28 patients had a history of BS (BS group) were identified. Of this BS group, 24 patients underwent a Roux-en-Y gastric bypass (RYGB), 3 a biliopancreatic diversion, 1 an adjustable gastric band, and no patients a sleeve gastrectomy. The proportion of patients with BS increased threefold over time during the study period. Patients in the BS group were significantly younger at diagnosis of sAH (44.3 years vs 52.4 years), were more frequently female, and had a higher body mass index and a higher grade of steatosis on liver biopsy. The correlation between BS and a younger age at diagnosis remained significant in a multivariate regression analysis. There were no differences in disease severity between both groups. Furthermore, there were no differences in corticosteroid response, 28-day, 90-day, or 1-year survival. CONCLUSION: Prior BS is independently associated with a younger age of presentation with sAH, but is not independently associated with a different disease severity or outcome. These findings support the need for early detection of AUD in patients who underwent BS, in particular RYGB.

Back to Work After Bariatric Surgery? A Belgian Population Study.

INTRODUCTION: Aside from an impact on health, obesity is also associated with higher social and economic costs such as impaired productivity, increased work absenteeism, and higher rates of unemployment. The aim of this study was to assess the effect of bariatric surgery on employment status in a large nationwide database, using data from all patients that underwent bariatric surgery in Belgium. METHODS: This is a retrospective analysis of all Belgian patients that underwent bariatric surgery between 2014 and 2015. The work status of these patients was examined yearly: 4 years before and 3 years after surgery. Increased employment after surgery was defined (1) as a reduction in days of unemployment and incapacity and (2) as the resumption of work among the unemployed. RESULTS: In total, 16,276 patients were included. The number of working people rose from 49.7% before to 61.2% 3 years after bariatric surgery, i.e., an increase of 11.5% between pre- and post-surgery. The largest improvement in reduction in unemployment was found in individuals who were absent from work for more than 9 months, namely, a reduction from 13.4 to 7.2%. In the population of unemployed patients, 20.9% became employed after bariatric surgery. CONCLUSION: We found an increase in employment rate and a decrease in work incapacity and unemployment after bariatric surgery. Higher rates of employment after bariatric surgery may also contribute to an increased cost-effectiveness of bariatric surgery. It would be interesting to research possible targeting strategies to increase the employment rate even more after bariatric surgery.

The impact of bariatric surgery on macronutrient malabsorption depends on the type of procedure.

Introduction: Bariatric surgery, currently the most effective treatment for morbidly obese patients, may induce macronutrient malabsorption depending on the type of procedure. Macronutrient malabsorption affects the supply of substrates to the colon, subsequent microbial fermentation and possibly colonic health. Methods: Using isotope technology, we quantified the extent of macronutrient and bile acid malabsorption and its impact on colonic protein fermentation in patients after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and in controls. Participants consumed a single test meal (day 0) that contained intrinsically labeled (13C, 15N, and 2H) egg protein for quantification of protein digestion, malabsorption and fermentation, respectively, together with a transit marker and a marker for bile acid malabsorption. They collected breath samples up to 6 h and all urine and stool for 48 and 72 h, respectively. Food intake was registered from day -3 to day 2. Results: Malabsorption of fat, protein and carbohydrates differed between groups (p = 0.040; p = 0.046; and p = 0.003, respectively) and was slightly higher in RYGB but not in SG patients compared to controls. Protein fermentation was increased in both RYGB and SG patients compared to controls (p = 0.001) and was negatively correlated to 2H-recovery as a marker of transit (ρ = -0.47, p = 0.013). Conclusion: The limited macronutrient malabsorption likely does not affect the nutritional status of the patient. However, the higher protein fermentation may affect colonic health and warrants further investigation.

Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity.

Bitter taste receptors (taste 2 receptors, TAS2Rs) serve as warning sensors in the lingual system against the ingestion of potentially poisonous food. Here, we investigated the functional role of TAS2Rs in the human gut and focused on their potential to trigger an additional host defense pathway in the intestine. Human jejunal crypts, especially those from individuals with obesity, responded to bitter agonists by inducing the release of antimicrobial peptides (α-defensin 5 and regenerating islet-derived protein 3 α [REG3A]) but also regulated the expression of other innate immune factors (mucins, chemokines) that affected E. coli growth. We found that the effect of aloin on E. coli growth and on the release of the mucus glycoprotein CLCA1, identified via proteomics, was affected by TAS2R43 deletion polymorphisms and thus confirmed a role for TAS2R43. RNA-Seq revealed that denatonium benzoate induced an NRF2-mediated nutrient stress response and an unfolded protein response that increased the expression of the mitokine GDF15 but also ADM2 and LDLR, genes that are involved in anorectic signaling and lipid homeostasis. In conclusion, TAS2Rs in the intestine constitute a promising target for treating diseases that involve disturbances in the innate immune system and body weight control. TAS2R polymorphisms may be valuable genetic markers to predict therapeutic responses.

Liraglutide for Weight Management in the Real World: Significant Weight Loss Even if the Maximal Daily Dose Is Not Achieved.

INTRODUCTION: Obesity is a global health challenge, and pharmacologic options are emerging. Once daily subcutaneous administration of 3 mg liraglutide, a glucagon like peptide-1 analogue, has been shown to induce weight loss in clinical trials, but real-world effectiveness data are scarce. METHODS: It is a single-centre retrospective cohort study of patients who were prescribed liraglutide on top of lifestyle adaptations after multidisciplinary evaluation. In Belgium, liraglutide is only indicated for weight management if the BMI is >30 kg/m2 or ≥27 kg/m2 with comorbidities such as dysglycaemia, dyslipidaemia, hypertension, or obstructive sleep apnoea. No indication is covered by the compulsory health care insurance. Liraglutide was started at 0.6 mg/day and uptitrated weekly until 3 mg/day or the maximum tolerated dose. Treatment status and body weight were evaluated at the 4-month routine visit. RESULTS: Between June 2016 and January 2020, liraglutide was prescribed to 115 patients (77% female), with a median age of 47 (IQR 37.7-54.0) years, a median body weight of 98.4 (IQR 90.0-112.2) kg, a BMI of 34.8 (IQR 32.2-37.4) kg/m2, and an HbA1c level of 5.6%. Five (4%) patients did not actually initiate treatment, 9 (8%) stopped treatment, and 8 (7%) were lost to follow-up. At the 4-month visit, the median body weight had decreased significantly by 9.2% to 90.8 (IQR 82.0-103.5) kg (p < 0.001). Patients using 3.0 mg/day (n = 60) had lost 8.0 (IQR 5.8-10.4) kg. The weight loss was similar (p = 0.9622) in patients that used a lower daily dose because of intolerance: 7.4 (IQR 6.2-9.6) kg for 1.2 mg (n = 3), 7.8 (IQR 4.1-7.8) kg for 1.8 mg (n = 16), and 9.0 (IQR 4.8-10.7) kg for 2.4 mg/day (n = 14). Weight loss was minimal if liraglutide treatment was not started or stopped prematurely (median 3.0 [IQR 0.3-4.8] kg, p < 0.001, vs. on treatment). Further analysis showed an additional weight reduction of 1.8 kg in the patients that had started metformin <3 months before the start of liraglutide (p < 0.001). The main reasons for liraglutide discontinuation were gastrointestinal complaints (n = 5/9) and drug cost (n = 2/9). CONCLUSION: In this selected group of patients, the majority complied with liraglutide treatment over the initial 4-month period and achieved a significant weight loss, irrespective of the maximally tolerated maintenance dose. Addition of metformin induced a small but significant additional weight loss.

Late complications of biliopancreatic diversion in an older patient: a case report.

BACKGROUND: In the mid-seventies, biliopancreatic diversion became popular as weight-loss surgery procedure. This bariatric procedure combines distal gastric resection and intestinal malabsorption, leading to greater weight loss and improvement of co-morbidities than other bariatric procedures. Nowadays, biliopancreatic diversion has become obsolete due to the high risk of nutritional complications. However, current patients with biliopancreatic diversions are aging. Consequently, geriatricians and general practitioners will encounter them more often and will be faced with the consequences of late complications. CASE PRESENTATION: A 74-year old female presented with weakness, recurrent falls, confusion, episodes of irresponsiveness, anorexia and weight loss. Her medical history included osteoporosis, herpes encephalitis 8 years prior and a biliopancreatic diversion (Scopinaro surgery) at age 52. Cerebral imaging showed herpes sequelae without major atrophy. Delirium was diagnosed with underlying nutritional deficiencies. Biochemical screening indicated vitamin A deficiency, vitamin E deficiency, zinc deficiency and severe hypoalbuminemia. While thiamin level and fasting blood glucose were normal. However, postprandial hyperinsulinemic hypoglycemia was observed with concomitant signs of confusion and blurred consciousness. After initiating parenteral nutrition with additional micronutrient supplementation, a marked improvement was observed in cognitive and physical functioning. CONCLUSIONS: Long-term effects of biliopancreatic diversion remain relatively underreported in older patients. However, the anatomical and physiological changes of the gastrointestinal tract can contribute to the development of metabolic and nutritional complications that may culminate in cognitive impairment, functional decline and delirium. Therefore, it is warranted to evaluate the presence of metabolic disturbances and nutritional complications in older patients after biliopancreatic diversion.

Psychosocial Consequences of Bariatric Surgery: Two Sides of a Coin: a Scoping Review.

This scoping review summarizes current evidence with regard to the impact of bariatric surgery on psychological health in adults with obesity. While a large body of evidence reports major metabolic benefit and improved quality of life, there is also ample evidence suggesting an increased incidence of self-harming behavior, a greater likelihood of developing an alcohol problem and higher rates of completed suicide among bariatric patients. Being able to identify the "at risk" patient population requires more longitudinal research into the risk factors for psychological complications after bariatric surgery. Bariatric surgery remains an extremely valuable long-term treatment option for managing obesity; however, there is a need to invest in mitigating psychological complications after the surgery, such as depression, alcohol consumption, and other self-harming behaviors.

Defining Global Benchmarks in Elective Secondary Bariatric Surgery Comprising Conversional, Revisional, and Reversal Procedures.

OBJECTIVE: To define "best possible" outcomes for secondary bariatric surgery (BS). BACKGROUND: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. METHODS: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. RESULTS: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ±â€Š10 years, 8.4 ±â€Š5.3 years after primary BS, with a BMI 35.2 ±â€Š7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. CONCLUSION: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Adaptations in gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass.

Linked to the growing obesity epidemic, demand for bariatric and metabolic surgery has increased, the most common procedures being sleeve gastrectomy and Roux-en-Y gastric bypass. Originally, bariatric procedures were described as purely restrictive, malabsorptive, or combined restrictive-malabsorptive procedures limiting food intake, nutrient absorption, or both. Nowadays, anatomical alterations are known to affect gastrointestinal physiology, which in turn affects the digestion and absorption of nutrients and drugs. Therefore, understanding gastrointestinal physiology is crucial to prevent postoperative nutritional deficiencies and to optimise postoperative drug therapy. Preclinical and clinical research indicates that sleeve gastrectomy accelerates liquid and solid gastric emptying and small intestinal transit, and increases bile acid serum levels, whereas its effects on gastrointestinal acidity, gastric and pancreatic secretions, surface area, and colonic transit remain largely unknown. Roux-en-Y gastric bypass diminishes gastric acid secretion, accelerates liquid gastric emptying, and increases bile acid serum levels, but its effects on intestinal pH, solid gastric emptying, intestinal transit time, gastric enzyme secretions, and surface area remain largely unknown. In this Review, we summarise current knowledge of the effects of these two procedures on gastrointestinal physiology and assess the knowledge gaps.

Gestational weight gain and postpartum weight retention after bariatric surgery: data from a prospective cohort study.

BACKGROUND: It is unknown whether international guidelines on gestational weight gain can be used in pregnancies after bariatric surgery. OBJECTIVES: To investigate gestational weight gain, intrauterine growth, and postpartum weight retention in postbariatric women. SETTING: 8 Belgian hospitals. METHODS: Prospective data from 127 postbariatric pregnancies from September 2014 through October 2018. Patients were grouped according to achievement of 2009 Institute of Medicine (IOM) guidelines. RESULTS: In 127 patients with a mean age of 30.2 years (standard deviation [SD], 4.7), the mean gestational weight gain was 12.5 kg (SD, 6.7). Of these patients, 24% (30 of 127) showed insufficient weight gain, 20% (26 of 127) showed adequate weight gain, and 56% (71 of 127) showed excessive weight gain. Of 127 patients, 27 (21%) had small-for-gestational-age infants. This peaked in the group with insufficient weight gain (47%; 95% confidence interval [CI], 29%-65%; P < .001). The prevalence of large-for-gestational-age infants was comparable between groups, although highest in the group with excessive weight gain (0% in those with insufficient weight gain, 4% in those with adequate weight gain, and 8% in those with excessive weight gain). Preterm births were recorded more in patients with insufficient weight gain (23%; 95% CI, 8%-38%; P = .048). The mean amounts of postpartum weight retained were 4.0 kg (SD, 7.4) at 6 weeks and 3.0 kg (SD, 9.1) at 6 months. Weight retention at 6 weeks (7.1 kg; 95% CI, 5.5-8.7; P < .001) and 6 months (8.3 kg; 95% CI, 4.5-12.2; P < .001) was highest in women gaining excessive weight. CONCLUSION: Achievement of IOM guidelines is low in postbariatric pregnancies. Insufficient weight gain increases the risk for small-for-gestational-age babies. Excessive weight gain increases weight retention after delivery and could precipitate weight regain. After bariatric surgery, women should be encouraged to achieve IOM recommendations.

Glucose Homeostasis, Fetal Growth and Gestational Diabetes Mellitus in Pregnancy after Bariatric Surgery: A Scoping Review.

BACKGROUND: Pregnancies in women with a history of bariatric surgery are becoming increasingly prevalent. Surgically induced metabolic changes benefit mother and child, but can also lead to some adverse pregnancy outcomes. Knowledge about glucose homeostasis in these pregnancies could elucidate some of the mechanisms behind these outcomes. This review focusses on glucose homeostasis and birth weight. METHODS: We considered papers dealing with glucose homeostasis, gestational diabetes mellitus (GDM) and/or small-for-gestational age infants (SGA) in pregnancies with a history of sleeve gastrectomy (SG) or Roux-en-y gastric bypass (RYGB). RESULTS: Since an OGTT is unreliable to diagnose GDM in a pregnancy after bariatric surgery, the true incidence of GDM is unknown. Alternative screening strategies are needed. Furthermore, these pregnancies are marked by frequent hypoglycemic events as well as wide and rapid glycemic excursions, an issue that is very likely underreported. There is a lack of uniformity in reporting key outcomes and a large variation in study design and control population. CONCLUSION: Alteration of glucose homeostasis in a pregnancy after bariatric surgery should be further studied using unequivocal definition of key concepts. Glycemic control may prove to be a modifiable risk factor for adverse pregnancy outcomes such as the delivery of an SGA baby.

Reversal of Roux-en-Y Gastric Bypass Fails to Facilitate the Management of Recalcitrant Hypocalcaemia Caused by Primary Hypoparathyroidism.

Roux-en-Y gastric bypass (RYGB) is thought to reduce calcium absorption from the gut. Here, we report the case of a patient with a RYGB, who developed primary hypoparathyroidism after a total thyroidectomy, leading to recalcitrant hypocalcaemia. Despite aggressive oral calcium and calcitriol supplementation, she remained hypocalcaemic and required intravenous (IV) calcium supplementation to control her symptoms, and to keep calcium serum levels within an acceptable range. Teriparatide treatment improved calcium levels marginally. This treatment, however, was poorly tolerated and ultimately stopped by the patient. As a last resort, reversal of RYGB was performed to improve calcium absorption from the gut. Unfortunately, IV calcium supplementation remained necessary. This case illustrates that the reversal of RYGB is not always a guarantee for success in managing recalcitrant hypocalcaemia.

The curious fate of bone following bariatric surgery: bone effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in mice.

BACKGROUND: Bone loss and increased fracture risk following bariatric surgery has been reported. We investigated whether the two most commonly performed surgeries, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), lead to bone loss. In addition, we examined whether fortification of the diet with calcium citrate prevents bone loss. METHODS: We used mouse models for SG and RYGB and compared bone loss with a group of sham mice with similar weight loss. All groups were switched at the time of surgery to a low-fat diet (LFD). We also examined whether fortification of the diet with calcium citrate and vitamin D was able to prevent bone loss. RESULTS: At 2 weeks we observed no major bone effects. However, at 8 weeks, both trabecular and cortical bone were lost to the same extent after SG and RYGB, despite increased calcium absorption and adequate serum levels of calcium, vitamin D, and parathyroid hormone (PTH). Diet fortification with calcium citrate and vitamin D was able to partially prevent bone loss. CONCLUSIONS: Both SG and RYGB lead to excess bone loss, despite intestinal adaptations to increase calcium absorption. Fortifying the diet with calcium citrate and vitamin D partly prevented the observed bone loss. This finding emphasizes the importance of nutritional support strategies after bariatric surgery, but also affirms that the exact mechanisms leading to bone loss after bariatric surgery remain elusive and thus warrant further research.