Séverine Ledoux

Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients

Obesity and type 2 diabetes (T2D) are associated with low-grade inflammation, activation of immune cells, and alterations of the gut microbiota. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial ligands, are present in blood and enriched in mucosal and inflamed tissues. Here, we analyzed MAIT cells in the blood and adipose tissues of patients with T2D and/or severe obesity. We determined that circulating MAIT cell frequency was dramatically decreased in both patient groups, and this population was even undetectable in some obese patients. Moreover, in both patient groups, circulating MAIT cells displayed an activated phenotype that was associated with elevated Th1 and Th17 cytokine production. In obese patients, MAIT cells were more abundant in adipose tissue than in the blood and exhibited a striking IL-17 profile. Bariatric surgery in obese patients not only improved their metabolic parameters but also increased circulating MAIT cell frequency at 3 months after surgery. Similarly, cytokine production by blood MAIT cells was strongly decreased after surgery. This study reveals profound MAIT cell abnormalities in patients harboring metabolic disorders, suggesting their potential role in these pathologies.

The impact of bariatric surgery on comorbidities and medication use among obese patients.

BackgroundThe risks and benefits of bariatric surgery have rarely been evaluated in large multiyear patient samples. This study identifies the short- and long-term impact of bariatric surgery on comorbidities and medication use among obese patients.MethodsA comprehensive analysis of 5,502 obese patients who underwent bariatric surgery was performed. Submissions of reimbursement claims, including diagnostics and medication use, were compared in the 90xa0days preceding the surgery and 30 up to 1,110xa0days following the surgery. Presurgery and postsurgery frequency counts were performed on diagnostics and medication use to identify trends.ResultsAmong 5,502 patients, significant decreases in the prevalence of reported comorbidities were observed during the short-term postsurgery period and sustained for up to 3xa0years of follow-up. Compared to the presurgery period, significant decreases (pu2009<u20090.05) were observed after 3xa0years for total cardiovascular disorders (43.6% vs. 14.2%), diabetes mellitus (19.9% vs. 7.7%), chronic obstructive pulmonary disease and other respiratory conditions (57.7% vs. 16.2%), diseases of the musculoskeletal system and connective tissue (32.6% vs. 27.7%), and mental disorders (30.7% vs. 14.8%). Over the same period, the frequency of medication use decreased significantly for a number of conditions including infections, pain, respiratory, cardiovascular, gastroenterologic, lipidemic, and diabetic conditions. Anemia, however, increased from 3.8% to 9.9%, and use of nutritional supplements increased significantly.ConclusionBariatric surgery was associated with significant reductions in reported claims for short- and long-term health outcomes and reduced medication use for major disease categories.

Traditional Anthropometric Parameters Still Predict Metabolic Disorders in Women With Severe Obesity

It is well established that fat distribution rather than the total quantity of fat is the major determinant of cardiovascular risk in overweight subjects. However, it is not known whether the concept of fat distribution still makes sense in severely obese subjects. Particularly, the role of visceral fat accumulation and/or of adipocyte hypertrophy in insulin resistance (IR) has not been studied in this population. Therefore, the aim of this study was to clarify the determinants of metabolic disorders in severely obese women. We performed a cross‐sectional study in 237 severely obese women (BMI >35 kg/m2). We assessed total body fat mass and fat distribution by anthropometric measurements (BMI and waist‐to‐hip ratio (WHR)) and by dual‐energy X‐ray absorptiometry (DXA). In 22 women, we measured subcutaneous and visceral adipocyte size on surgical biopsies. Mean BMI was 44 ± 7 kg/m2 (range 35–77), mean age 37 ± 11 years (range 18–61). Lipid parameters (triglycerides, high‐density lipoprotein cholesterol) and IR markers (fasting insulin and homeostasis model assessment (HOMA) index) correlated with fat distribution, whereas inflammatory parameters (C‐reactive protein, fibrinogen) correlated only with total fat mass. An association was observed between android fat distribution and adipocyte hypertrophy. Visceral adipocyte hypertrophy was associated with both IR and hypertension, whereas subcutaneous fat‐cell size was linked only to hypertension. Our results obtained in a large cohort of women showed that fat distribution still predicts metabolic abnormalities in severe obesity. Furthermore, we found a cluster of associations among fat distribution, metabolic syndrome (MS), and adipocyte hypertrophy.

Predictive Factors of Weight Loss 1 Year after Laparoscopic Gastric Bypass in Obese Patients

BackgroundSubstantial weight loss is achieved in majority of severely obese subjects undergoing laparoscopic gastric bypass (LGBP) but some fail to obtain expected results. Our aim was to identify preoperative factors that could influence weight loss (WL) 1xa0year after LGBP.MethodsWe studied the predictive value of clinical, biological, and dietary preoperative factors on weight loss in obese patients referred for LGBP. WL was assessed according to mean absolute weight loss (AWL) and mean percent excess weight loss (%EWL) 1xa0year after LGBP.ResultsOne hundred twenty-three subjects were included (112 women, age 42u2009±u200910xa0years; weight 127u2009±u200923xa0kg; BMI 47u2009±u20098xa0kg/m2). Mean AWL was 39.4u2009±u200910.5xa0kg at 1xa0year, corresponding to a mean %EWL of 70.5u2009±u200921.2%. AWL was positively correlated with initial weight, BMI, and energy intake and negatively with age, female sex, and treatment for hypertension and diabetes. %EWL was negatively correlated with initial weight, BMI, and positively correlated with triglycerides and ferritinemia. In multivariate analysis, %EWL was negatively correlated only with initial BMI (pu2009<u20090.001). AWL was positively correlated with initial BMI and male sex (both pu2009<u20090.001), and negatively correlated with protein intake (pu2009=u20090.039) and treatment for diabetes (pu2009=u20090.021), but not with biomarkers of diabetes and insulin resistance.ConclusionInitial BMI appears to be a strong determinant of individual WL, but predictive factors differ when WL was expressed as %EWL or AWL. The treatment of diabetes rather than diabetes itself appears to affect WL.

Link between Adipose Tissue Angiogenesis and Fat Accumulation in Severely Obese Subjects

BACKGROUNDnWhite adipose tissue (WAT) can rapidly expand or regress under different nutritional conditions. The role of angiogenesis in the expandability of human adipose tissue is established. However, whether sc and omental WAT (scWAT and oWAT) angiogenesis could influence fat distribution and metabolic diseases is not known.nnnAIMnThe aim of this study was to analyze whether the capacity of angiogenesis in scWAT and oWAT correlates with fat accumulation and fat loss, fat distribution, adipocyte hypertrophy, and metabolic disorders in obese subjects.nnnMETHODSnSamples of scWAT and oWAT were obtained during bariatric surgery in 29 obese nondiabetic subjects. Vascular density and inflammatory infiltrate were analyzed by immunohistochemistry, and expression of angiogenic genes was analyzed by quantitative PCR. These parameters were correlated with anthropometric and metabolic parameters.nnnRESULTSnVascular density of scWAT correlated positively with body mass index, whereas vascular density of the oWAT correlated with waist circumference. There was no correlation of markers of angiogenesis and metabolic disorders. The number of vessels per adipocyte and the expression level of receptor 2 of vascular endothelial growth factor correlated with adipocyte area in scWAT and oWAT. Finally, weight loss after bariatric surgery correlated negatively with adipocyte hypertrophy and vascular density and positively with inflammation and angiogenesis of WAT.nnnCONCLUSIONnAngiogenesis may influence WAT expansion and plasticity but does not appear to be involved in the development of insulin resistance in subjects with severe obesity.

Serum vitamin D increases with weight loss in obese subjects 6 months after Roux-en-Y gastric bypass.

BackgroundMalabsorptive surgical procedures lead to deficiencies in fat-soluble vitamins. However, results concerning serum vitamin D (25OHD) after gastric bypass (GBP) are controversial. The aim of the study was to assess the influence of GBP on 25OHD and calcium metabolism.MethodsParameters of calcium metabolism were evaluated in 202 obese subjects before and 6xa0months after GBP. Thirty of them were matched for age, gender, weight, skin color, and season with 30 subjects who underwent sleeve gastrectomy (SG). A multivitamin preparation that provides 200 to 500xa0IU vitamin D3 per day was systematically prescribed after surgery.ResultsIn the 202 patients after GBP, serum 25OHD significantly increased from 13.4u2009±u20099.1 to 22.8u2009±u200911.3xa0ng/ml (pu2009<u20090.0001), whereas parathyroid hormone (PTH) did not change. Despite a decrease in calcium intake (pu2009<u20090.0001) and urinary calcium/creatinine ratio (pu2009=u20090.015), serum calcium increased after GBP (pu2009<u20090.0001). Preoperatively, 91xa0% of patients had 25OHD insufficiency (<30xa0ng/ml), 80xa0% deficiency (<20xa0ng/ml), and 19xa0% secondary hyperparathyroidism (>65xa0pg/ml) vs. 76, 44, and 17xa0%, respectively, following GBP. Serum 25OHD was negatively correlated with BMI at 6xa0months after GBP (Ru2009=u2009−0.299, pu2009<u20090.0001). In the two groups of 30 subjects, serum 25OHD and PTH did not differ at 6xa0months after GBP or SG.ConclusionsAt 6xa0months after GBP, serum 25OHD significantly increased in subjects supplemented with multivitamins containing low doses of vitamin D. These data suggest that weight loss at 6xa0months after surgery has a greater influence on vitamin D status than malabsorption induced by GBP.

Cardiovascular effects of French horn playing

would have conferred him a predicted 5-year survival near zero. Reports on anti-HIV CD8 T lymphocyte activity have identified soluble factors secreted by these cells-namely, RANTES, macrophage inflammatory proteins-a, MIPI-P, and interleukin-16 (IL-1 6),5 which have dose-related antiviral effects against HIV-1, HIV-2, and the closely related simian immunodeficiency virus. In the case of the first three chemokines, this activity is probably mediated by CC-CKR5, a membrane protein that seems to function as a coreceptor of the CD4 molecule in HIV infection. In the case of IL-16, the precise mechanism is as yet unknown, although it does bind to the CD4 receptor. We believe that some CD8 Tlymphocyte mediated immune function may have had a compensatory role in our patient.

P265 Apnée du sommeil et glucorégulation : quels sont les déterminants de l’association ?

Introduction Le syndrome d’apnee du sommeil (SAS) est associe a l’âge et a l’obesite, deux facteurs de risque majeurs de diabete. Dans l’association entre SAS et diabete, on ne sait pas bien ce qui est du a l’âge et l’obesite, et ce qui est rajoute par les consequences du SAS elles-memes, hypoxie nocturne et desordres du sommeil. Nous avons analyse les parametres de polygraphie nocturne dans une cohorte de femmes obeses non diabetiques. Patients et methodes 237 femmes, consecutives, ayant eu une exploration polygraphique du sommeil, et dont 106 ont eu une mesure de masse grasse par Dexa. Analyse multivariee des parametres associes au HOMA et a l’HbA1c. Resultats Dans cette population de femmes avec obesite morbide (IMC 44xa0±xa07xa0kg/m2), âgees de 36xa0±xa011 ans, la prevalence du SAS (indice d’apnee-hypopnee (IAH) > 15) etait de 63 %, l’IAH moyen 27xa0±xa022, la saturation en oxygene moyenne (SaO2m) 95xa0±xa02 %, le HOMA 2,8xa0±xa01,7 et l’HbA1c 5,5xa0±xa00,5 %. En analyse multivariee, âge, BMI et rapport taille/hanche (RTH) etaient des determinants de l’IAH, mais pas la masse grasse mesuree en Dexa. Apres ajustement pour l’âge, le BMI (ou la masse grasse en Dexa) et le RTH, l’indice HOMA n’etait associe ni a l’IAH ni a la SaO2m. L’HbA1c n’etait associee ni a l’IAH ni a la SaO2m apres ajustement pour âge, BMI et RTH. Les patientes avec SAS ne differaient pas des autres pour le HOMA et l’HbA1c, apres ajustement pour âge, BMI et RTH. Discussion Nos donnees confirment que le SAS est associe a la repartition des graisses plutot qu’a la masse grasse elle-meme. Nos resultats doivent etre ponderes par le fait qu’ils ont ete obtenus dans une population de femmes, relativement jeunes et tres obeses. Le SAS n’apparait pas, en soi, un determinant propre de la resistance a l’action de l’insuline ou de la glycemie. Ces donnees suggerent que l’association du SAS au diabete est essentiellement le fait de determinants communs.

P254 - Insulinorésistance, angiogenèse et taille adipocytaire chez le sujet obèse

Introduction Il est desormais bien etabli que l’accumulation de tissu adipeux visceral influence la survenue des complications metaboliques de l’obesite. Les capacites d’adipogenese du tissu adipeux (TA) sont liees au developpement de sa vascularisation. Tres peu de travaux ont compare les proprietes d’angiogenese des tissus adipeux sous-cutane (SAT) et visceral (VAT) chez l’homme. Notre objectif a ete de tester l’hypothese selon laquelle des differences dans les capacites d’angiogenese du SAT et du VAT pourraient influencer leur expansion, le degre d’hypertrophie adipocytaire et les desordres metaboliques associes. Materiels et methodes Des prelevements de SAT et de VAT ont ete obtenus chez 29 patients obeses, non diabetiques, au cours d’une chirurgie bariatrique. La densite vasculaire et l’infiltrat inflammatoire ont ete analyses par immunohistochimie, et l’expression des genes de l’angiogenese par PCR quantitative. Ces resultats ont ete correles au phenotype clinique et biologique des patients. Resultats Nous avons confirme que la taille des adipocytes etait plus importante dans le SAT que le VAT (2 481xa0±xa02 vs 2 117xa0±xa02, pxa0=xa00,01). La densite vasculaire (2,58 vs 3,12 vaisseaux/10 000xa0±xa02, pxa0=xa00,03), l’inflammation et l’expression des facteurs pro-angiogeniques etaient plus faibles dans le SAT. De plus, l’expression du recepteur 2 du VEGF, le principal facteur angiogenique implique dans l’angiogenese du tissu adipeux, etait correlee positivement a la taille adipocytaire (rxa0=xa00,48, pxa0=xa00,01 et rxa0=xa00,43, pxa0=xa00,02) dans les 2 tissus. Enfin, la densite vasculaire du SAT et du VAT etait correlee au poids, mais seule la densite vasculaire du VAT etait associee au tour de taille. Nous n’avons pas retrouve de relation entre les marqueurs d’angiogenese et les desordres metaboliques quelle que soit l’origine du TA. Conclusion Nos resultats suggerent que les capacites d’angiogenese du tissu adipeux pourraient influencer la repartition des graisses et le degre d’hypertrophie adipocytaire, mais ne semblent pas etre impliquees dans le developpement de l’insulino-resistance.