Predictors and weight impact of postbariatric hypoglycemia after Roux-en-Y gastric bypass surgery: a prospective observational cohort study.

BACKGROUND: Postbariatric hypoglycemia (PBH) is a challenging condition affecting quality of life of patients after bariatric surgery. However, its incidence and predictive factors remain debated. OBJECTIVES: To determine the incidence of PBH, identify predictors of PBH and assess its association with weight trajectory after bariatric surgery. SETTING: University Hospital. METHODS: Prospective observational cohort study including 222 nondiabetic patients who underwent Roux-en-Y gastric bypass between 2014 and 2021, had an oral glucose tolerance test (OGTT) and/or A1C (glycated hemoglobin) measurement prior to surgery and were followed for at least 12 months. Diagnosis of PBH was made when symptoms of hypoglycemia were accompanied by a postprandial plasma glucose level < 3.9 mmol/l or a glycemia < 3.9 mmol/l during continuous glucose monitoring, with resolution of symptomatology after carbohydrate consumption. Univariable and multivariable logistic regression analyses were performed to identify factors associated with PBH. RESULTS: Out of 222 patients, 71 (32%) were diagnosed with PBH. The highest incidence rate was observed at 2 years postbariatric surgery with a cumulative incidence of 26.5%. Predictive factors for higher risk of PBH were younger age at surgery (OR = .97; 95% CI: .94-.99; P = .049) and early dumping syndrome (OR = 3.05; 95% CI: 1.62-6.04; P = .0008). In multivariable logistic regression, higher glycemia at 2 hours during preoperative OGTT was associated with lower risk of PBH (OR = .8; 95% CI: .63-.98; P = .04). PBH was not associated with weight trajectory after surgery in our cohort. CONCLUSIONS: Younger age at time of surgery and lower blood glucose at 120 minute during preoperative OGTT are risk factors for PBH. Early dumping syndrome is significantly associated with PBH and could be used as a red flag to help identify patients at risk of PBH.

Intravenous ferric carboxymaltose is associated with lowering of plasma phosphate levels in patients with gastric bypass surgery: a retrospective case series.

AIMS: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass. METHODS: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering. RESULTS: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9-36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (<0.8 mmol/l) after ferric carboxymaltose infusion. Median plasma phosphate significantly decreased by 0.33 mmol/l (IQR 0.14-0.49) (p<0.0001). Multiple linear regression identified the ferric carboxymaltose dose as the only risk factor significantly associated with the magnitude of serum phosphate lowering, with an additional mean loss of 0.26 mmol/l with a 500 mg infusion compared to a 250 mg infusion (p = 0.020). CONCLUSION: Ferric carboxymaltose infusions substantially decreased plasma phosphate levels in patients with previous Roux-en-Y gastric bypass. Compared to a dose of 250 mg, infusion of a dose of 500 mg ferric carboxymaltose decreased the plasma phosphate further in this population.

A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion.

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.

[Focus on obesity drug treatments]. / Focus sur les traitements médicamenteux de l'obésité.

The management of obesity is changing dramatically with the emergence of new drug treatments. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for this indication in Switzerland, and approval is currently being sought for a GLP-1 and glucose-dependent insulinotropic polypetide (GIP) co-agonist. Reimbursement conditions are restrictive, and patients are given only one opportunity to achieve the weight loss required for continued reimbursement. The popularity of these treatments has led to worldwide stock-outs for several months now, and it is essential that prescribers respect the indications so as not to prejudice obese patients. This article provides a review of the treatments available and the conditions under which they are reimbursed, as well as those that should be reimbursed soon.

La prise en charge de l'obésité est profondément modifiée par l'essor de nouveaux traitements médicamenteux. Les agonistes du récepteur du glucagon-like peptide-1 (GLP-1) sont approuvés dans cette indication en Suisse et une approbation est en cours d'analyse pour un coagoniste du GLP-1 et du glucose-dependent insulinotropic polypetide (GIP). Les conditions de remboursement sont cependant strictes et les patients ne bénéficient que d'une seule opportunité pour obtenir les pertes pondérales qui autorisent la poursuite du remboursement. La popularité de ces traitements occasionne des ruptures de stocks depuis plusieurs mois au niveau mondial et il est essentiel que les prescripteurs respectent les indications afin de ne pas prétériter les patients en situation d'obésité. Cet article propose un rappel des traitements disponibles et les conditions encadrant leur remboursement, ainsi que ceux qui le seront prochainement.

[Pregnancy and bariatric surgery : from pre-conception to postpartum]. / Grossesse et chirurgie bariatrique : du préconceptionnel au postpartum.

Bariatric surgery is regularly offered to women of childbearing age. Pregnancy after such surgery should be planned and requires special attention. Some complications associated with obesity during pregnancy are reduced after bariatric surgery, but reduced dietary intake and malabsorption can cause nutritional deficiencies, that need to be carefully screened for and supplemented. Dietary management is recommended, and any unusual abdominal pain should be referred to a bariatric surgeon. We offer a summary of recommendations for appropriate follow-up of these pregnancies.

La chirurgie bariatrique est régulièrement proposée à des femmes en âge de procréer. Une grossesse après une telle chirurgie devrait être planifiée et demande une attention particulière. Certaines complications liées à l'obésité durant la grossesse sont réduites après une chirurgie bariatrique mais une diminution des apports alimentaires et la malabsorption peuvent engendrer des carences nutritionnelles qui doivent être attentivement dépistées et supplémentées. Une prise en charge diététique est recommandée et toute douleur abdominale inhabituelle doit faire demander l'avis d'un chirurgien bariatrique. Nous proposons une synthèse des recommandations pour un suivi adéquat de ces grossesses.

cGAS-STING drives ageing-related inflammation and neurodegeneration.

Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease1. Multiple factors can contribute to ageing-associated inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling and their impact in natural ageing remain unclear. Here we show that the cGAS-STING signalling pathway, which mediates immune sensing of DNA3, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglial transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia, defining a mechanism by which cGAS-STING signalling is engaged in the ageing brain. Single-nucleus RNA-sequencing analysis of microglia and hippocampi of a cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglial states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS-STING pathway as a driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS-STING signalling as a potential strategy to halt neurodegenerative processes during old age.

Impact of Preoperative Psychiatric Profile in Bariatric Surgery on Long-term Weight Outcome.

BACKGROUND: Conflicting results have been reported regarding the predictive value of preoperative psychological assessment and weight outcome after bariatric surgery. This might be attributed to different factors affecting early weight loss and long-term weight loss. Herein, we investigated whether preoperative psychiatric profile was associated with preoperative BMI and with both early (1 year) and long-term (5 years) weight loss after Roux-en-Y gastric bypass (RYGB). METHODS: Prospective observational cohort study of patients undergoing RYGB between 2013 and 2019. Symptoms related to anxiety, depression, eating disorder, and alcohol use disorders were assessed by employing validated, specific psychometric tests (STAI-S/T, BDI-II, BITE, AUDIT-C) prior to surgery. Pre-operative BMI, early weight loss (1 year), and long-term weight evolution (up to 5 years) were registered. RESULTS: Two hundred thirty six patients (81% women) were included in the present study. Linear longitudinal mixed model showed a significant effect of preoperative high anxiety (STAI-S) on long-term weight outcome, after controlling for gender, age and type 2 diabetes. Patient with high preoperative anxiety score regained weight faster than those experiencing low anxiety (each year percent excess BMI loss (%EBMIL) - 4.02%, ± 1.72, p = 0.021). No other pre-operative psychiatric symptoms have been shown to have an impact on long-term weight loss. In addition, no significant association was found between any of the pre-operative psychiatric variables and pre-operative BMI, or early weight loss (%EBMIL) at 1-year post-RYGB. CONCLUSION: Herein we identified high anxiety score (STAI-S) as a predictor for long-term weight regain. Thus, long-term psychiatric surveillance of these patients and the development of tailored management tools could serve as a means to prevent weight regain.

The Influence of a Roux-en-Y Gastric Bypass on Plasma Concentrations of Antidepressants.

PURPOSE: Roux-en-Y gastric bypass (RYGB) involves alterations of the gastrointestinal tract resulting in altered absorption. Patients with obesity have a higher prevalence of depression, and antidepressants are often prescribed. Alterations caused by RYGB could modify drug bioavailability and cause potential subtherapeutic plasma concentrations, increasing the risk of depressive relapse. The aim of this study was to describe the evolution of trough drug dose-normalized antidepressant plasma concentrations before and after RYGB. MATERIALS AND METHODS: This naturalistic prospective case series considers patients with trough plasma concentrations in a 1-year timeframe before and after RYGB. Only antidepressants prescribed to at least three patients were included in the present study. RESULTS: Thirteen patients (n = 12 females, median age 44 years, median BMI before intervention = 41.3 kg/m2) were included. Two patients were treated concurrently with fluoxetine and trazodone; the remaining patients were all treated with antidepressant monotherapy. Therapeutic drug monitoring (TDM) values for duloxetine (n = 3), escitalopram (n = 4), fluoxetine (n = 4), and trazodone (n = 4) before (median 4.7 weeks) and after (median 21.3 weeks) RYGB intervention were analyzed. Compared to preintervention, median [interquartile range] decreases in dose-normalized trough plasma concentrations for duloxetine (33% [- 47; - 23]), escitalopram (43% [- 51; - 31]), fluoxetine (9% [- 20; 0.2]), and trazodone (16% [- 29; 0.3]) were observed. CONCLUSION: This study shows a decrease in plasma antidepressant concentrations following RYGB. TDM before and after RYGB, in addition to close monitoring of psychiatric symptomatology, may help optimize antidepressant treatment after bariatric surgery. These results also highlight the need for prospective studies assessing the clinical evidence available through TDM in these patients.