Hypothalamic Inflammation Improves Through Bariatric Surgery, and Hypothalamic Volume Predicts Short-Term Weight Loss Response in Adults With or Without Type 2 Diabetes.

OBJECTIVE: Preclinical research implicates hypothalamic inflammation (HI) in obesity and type 2 diabetes pathophysiology. However, their pathophysiological relevance and potential reversibility need to be better defined. We sought to evaluate the effect of bariatric surgery (BS) on radiological biomarkers of HI and the association between the severity of such radiological alterations and post-BS weight loss (WL) trajectories. The utility of cerebrospinal fluid large extracellular vesicles (CSF-lEVs) enriched for microglial and astrocyte markers in studying HI was also explored. RESEARCH DESIGN AND METHODS: We included 72 individuals with obesity (20 with and 52 without type 2 diabetes) and 24 control individuals. Participants underwent lumbar puncture and 3-T MRI at baseline and 1-year post-BS. We assessed hypothalamic mean diffusivity (MD) (higher values indicate lesser microstructural integrity) and the volume of the whole and main hypothalamic subregions. CSF-lEVs enriched for glial and astrocyte markers were determined by flow cytometry. RESULTS: Compared with control group, the obesity and type 2 diabetes groups showed a larger volume and higher MD in the hypothalamic tubular inferior region, the area encompassing the arcuate nucleus. These radiological alterations were positively associated with baseline anthropometric and metabolic measures and improved post-BS. A larger baseline tubular inferior hypothalamic volume was independently related to lesser WL 1 and 2 years after BS. CSF-lEVs did not differ among groups and were unrelated to WL trajectories. CONCLUSIONS: These findings suggest HI improvement after BS and may support a role for HI in modulating the WL response to these interventions.

Safety and performance of a hybrid closed-loop insulin delivery system with carbohydrate suggestion in adults with type 1 diabetes prone to hypoglycemia.

AIMS: To evaluate the safety and performance of a hybrid closed-loop (HCL) system with automatic carbohydrate suggestion in adults with type 1 diabetes (T1D) prone to hypoglycemia. METHODS: A 32-hour in-hospital pilot study, including a night period, 4 meals and 2 vigorous unannounced 45-minute aerobic sessions, was conducted in 11 adults with T1D prone to hypoglycemia. The primary outcome was the percentage of time in range 70-180 mg/dL (TIR). Main secondary outcomes were time below range < 70 mg/dL (TBR < 70) and < 54 (TBR < 54). Data are presented as median (10th-90th percentile ranges). RESULTS: The participants, 6 (54.5%) men, were 24 (22-48) years old, and had 22 (9-32) years of T1D duration. All of them regularly used an insulin pump and a continuous glucose monitoring system. The median TIR was 78.7% (75.6-91.2): 92.7% (68.2-100.0) during exercise and recovery period, 79.3% (34.9-100.0) during postprandial period, and 95.4% (66.4-100.0) during overnight period. The TBR < 70 and TBR < 54 were 0.0% (0.0-6.6) and 0.0% (0.0-1.2), respectively. A total of 4 (3-9) 15-g carbohydrate suggestions were administered per person. No severe acute complications occurred during the study. CONCLUSIONS: The HCL system with automatic carbohydrate suggestion performed well and was safe in this population during challenging conditions in a hospital setting.

Bariatric Surgery Outcomes in Patients with Chronic Kidney Disease.

Obesity increases the risk of developing chronic kidney disease (CKD), which has a major negative impact on global health. Bariatric surgery (BS) has demonstrated a substantial improvement of obesity-related comorbidities and thus, it has emerged as a potential therapeutic tool in order to prevent end-stage renal disease. A limited number of publications to date have examined the beneficial effects and risks of BS in patients with non-advanced stages of CKD. We aimed to investigate the safety of BS in patients with CKD stages 3-4 (directly related or not to obesity) and both the metabolic/renal outcomes post-BS. A total of 57 individuals were included (n = 19 for CKD-group; n = 38 for patients with obesity, but normal eGFR [control-group]). Weight loss and obesity comorbidities resolution after BS were similar in both groups. Renal function (eGFR [CKD-EPI]) improved significantly at the 1-year follow-up: Δ10.2 (5.2-14.9) (p < 0.001) for CKD-group and Δ4.0 (-3.9-9.0) mL/min/1.73 m2 (p = 0.043) for controls. Although this improvement tended to decrease in the 5-year follow-up, eGFR remained above its basal value for the CKD-group. Noteworthy, eGFR also improved in those patients who presented CKD not directly attributed to obesity. For patients with CKD, BS appears to be safe and effective regarding weight loss and obesity comorbidities resolution, irrespective of the main cause of CKD (related or not to obesity).

Effects of Bariatric Surgery on Blood and Vascular Large Extracellular Vesicles According to Type 2 Diabetes Status.

CONTEXT: Large extracellular vesicles (lEVs) enriched for endothelial and blood cell markers are increased in metabolic conditions such as obesity or type 2 diabetes (T2D), actively contribute to the atherosclerotic process, and have been identified as diagnostic and prognostic biomarkers for cardiovascular disease (CVD). Although bariatric surgery (BS) in individuals with obesity is related to decreased cardiovascular (CV) risk and increased life expectancy, after BS these subjects are still at higher CV risk than the general population. OBJECTIVE: We aimed to compare the lEV profiles between individuals with obesity, with or without T2D, before and 1 year after BS, and normal-weight controls. METHODS: Prospective longitudinal study with individuals eligible for BS, with or without T2D (T2D and OB groups, respectively) and healthy controls (HC group) matched by age and sex. The concentration and phenotype of lEVs were assessed by flow cytometry. RESULTS: The study cohort included 108 individuals (age 48.0 ± 10.5 years; 84.3% females). Before BS, the OB group presented higher concentrations of lEV enriched for endothelial and blood cell biomarkers than the HC group, but lower concentrations than those observed in the T2D group (P < .05). BS resulted in a significant reduction in most of the lEVs enriched for cell-specific markers in both subgroups. lEV differences between OB and T2D groups were no longer observed after BS (P > .05). However, compared with HC group, OB and T2D groups still showed increased concentrations of lEVs enriched for platelet and endothelial cell markers (P < .05). CONCLUSION: At 1 year after BS, lEV concentrations remain above the physiological range. These abnormalities might contribute to explaining the increased CV risk after BS and underscore the importance of long-term CV risk factor control in post-BS individuals.

Bariatric Surgery Outcomes in Patients with Kidney Transplantation.

Obesity and kidney transplantation (KTx) are closely related. Obesity increases the risk of chronic kidney disease and can be a relative contraindication for KTx. Besides, KTx recipients are predisposed to obesity and its comorbidities. Consequently, bariatric surgery (BS) emerges as a powerful therapeutic tool either before or after KTx. Since evidence regarding the best approach is still scarce, we aimed to describe renal and metabolic outcomes in a single centre with more than 15-year experience in both surgeries. METHODS: A retrospective study including patients who had received a KTx either before or after BS. Usual metabolic and renal outcomes, but also new variables (as renal graft dysfunction) were collected for a minimum follow-up of 1-year post-BS. RESULTS: A total of 11 patients were included: n = 6 (BS-post-KTx) and n = 5 (BS-pre-KTx). One patient was assessed in both groups. No differences in the main outcomes were identified, but BS-post-KTx group tended to gain more weight during the follow-up. The incidence of renal graft dysfunction was comparable (4/6 for BS-post-KTx, 3/5 for BS-pre-KTx) between groups. CONCLUSIONS: BS in patients with KTx appears to be safe and effective attending to metabolic and renal outcomes. These results seem irrespective of the time course, except for weight regain, which appears to be a common pattern in the BS-post-KTx group.

Positive Effects of a Mediterranean Diet Supplemented with Almonds on Female Adipose Tissue Biology in Severe Obesity.

It has been suggested that weight-loss-independent Mediterranean diet benefits on cardiometabolic health and diabetes prevention may be mediated, at least in part, through the modulation of white adipose tissue (WAT) biology. This study aimed to evaluate the short-term effects of a dietary intervention based on the Mediterranean diet supplemented with almonds (MDSA) on the main features of obesity-associated WAT dysfunction. A total of 38 women with obesity were randomly assigned to a 3-month intervention with MDSA versus continuation of their usual dietary pattern. Subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies were obtained before and after the dietary intervention, and at the end of the study period, respectively. MDSA favored the abundance of small adipocytes in WAT. In SAT, the expression of angiogenesis genes increased after MDSA intervention. In VAT, the expression of genes implicated in adipogenesis, angiogenesis, autophagy and fatty acid usage was upregulated. In addition, a higher immunofluorescence staining for PPARG, CD31+ cells and M2-like macrophages and increased ADRB1 and UCP2 protein contents were found compared to controls. Changes in WAT correlated with a significant reduction in circulating inflammatory markers and LDL-cholesterol levels. These results support a protective effect of a Mediterranean diet supplemented with almonds on obesity-related WAT dysfunction.

Control de la glucemia durante el ejercicio físico aeróbico y anaeróbico mediante un nuevo sistema de páncreas artificial / Blood glucose monitoring during aerobic and anaerobic physical exercise using a new artificial pancreas system

Objetivo: Evaluar de forma exploratoria un sistema de páncreas artificial durante la realización de ejercicio aeróbico (EAe) y anaeróbico (EAn). Métodos: Ensayo clínico piloto con 5 sujetos con diabetes tipo 1 (4 hombres) de 37±10,9 años, 21,2±12,2 años de evolución de la diabetes tipo 1, usuarios de infusor de insulina y una HbA1c de 7,8±0,5%. Cada uno de los pacientes realizó 3 estudios de EAe y 3 de EAn. El control de la glucemia se realizó mediante el algoritmo de páncreas artificial durante el ejercicio y las 4h posteriores al mismo. Previo al inicio del ejercicio físico se administraron 23g de hidratos de carbono. Resultados: La media de glucosa fue de 124,0±25,1mg/dL en los estudios de EAe y de 152,1±34,1mg/dL en los de EAn. Los porcentajes de tiempo en 70-180, >180 y <70mg/dL fueron: 89,8±18,6% y 75,9±27,6%; 7,7±18,4% y 23,2±28,0%; 2,5±6,3% y 1,0±3,6% durante el EAe y EAn, respectivamente. Únicamente fueron necesarios 6 rescates con 15g de hidratos de carbono en el total de los estudios (4 en EAe y 2 en EAn). La dosis total de insulina durante las 5h de estudio en los estudios de EAe fue de 3,1±1,0UI y de 3,5±1,3UI en los EAn. Conclusiones: La respuesta glucémica al EAe y al EAn es diferente. El sistema de páncreas artificial evaluado parece controlar de forma eficaz y segura la glucemia durante el ejercicio y las 4h posteriores al mismo, aunque es necesario el diseño de nuevas estrategias de control que minimicen la intervención del paciente

Aim: To assess an artificial pancreas system during aerobic (AeE) and anaerobic exercise (AnE). Methods: A pilot clinical trial on five subjects with type 1 diabetes (4 males) aged 37±10.9 years, diabetes diagnosed 21.2±12.2 years before, insulin pump users, and with a mean HbA1c level of 7.8±0.5%. Every subject did three AeE and three AnE sessions. Blood glucose levels were monitored by the artificial pancreas system during exercise and up to four hours later. Before the start of exercise, 23g of carbohydrates were administered orally. Results: The mean glucose level was 124.0±25.1mg/dL in the AeE studies and 152.1±34.1mg/dL in the AnE studies. Percent times in the different glucose ranges of 70-180, >180 and <70mg/dL were 89.8±18.6% and 75.9±27.6%; 7.7±18.4% and 23.2±28.0%; and 2.5±6.3% and 1.0±3.6% during the AeE and AnE sessions, respectively. Only six rescues with carbohydrates (15g) were required during the studies (4 in AeE and 2 in AnE). Total insulin dose during the five hours of the study was 3.1±1.0IU in the AeE studies and 3.5±1.3IU in the AnE studies. Conclusions: Blood glucose response to AeE and AnE exercise is different. The evaluated artificial pancreas system appeared to achieve effective and safe blood glucose control during exercise and up to four hours later. However, new control strategies that minimize patient intervention should be designed

Blood glucose monitoring during aerobic and anaerobic physical exercise using a new artificial pancreas system. / Control de la glucemia durante el ejercicio físico aeróbico y anaeróbico mediante un nuevo sistema de páncreas artificial.

AIM: To assess an artificial pancreas system during aerobic (AeE) and anaerobic exercise (AnE). METHODS: A pilot clinical trial on five subjects with type 1 diabetes (4 males) aged 37±10.9 years, diabetes diagnosed 21.2±12.2 years before, insulin pump users, and with a mean HbA1c level of 7.8±0.5%. Every subject did three AeE and three AnE sessions. Blood glucose levels were monitored by the artificial pancreas system during exercise and up to four hours later. Before the start of exercise, 23g of carbohydrates were administered orally. RESULTS: The mean glucose level was 124.0±25.1mg/dL in the AeE studies and 152.1±34.1mg/dL in the AnE studies. Percent times in the different glucose ranges of 70-180, >180 and <70mg/dL were 89.8±18.6% and 75.9±27.6%; 7.7±18.4% and 23.2±28.0%; and 2.5±6.3% and 1.0±3.6% during the AeE and AnE sessions, respectively. Only six rescues with carbohydrates (15g) were required during the studies (4 in AeE and 2 in AnE). Total insulin dose during the five hours of the study was 3.1±1.0IU in the AeE studies and 3.5±1.3IU in the AnE studies. CONCLUSIONS: Blood glucose response to AeE and AnE exercise is different. The evaluated artificial pancreas system appeared to achieve effective and safe blood glucose control during exercise and up to four hours later. However, new control strategies that minimize patient intervention should be designed.

Gastrointestinal Hormones and Weight Loss Maintenance Following Roux-en-Y Gastric Bypass.

CONTEXT: Factors underlying variable weight loss (WL) after Roux-en-Y gastric bypass (RYGB) are poorly understood. OBJECTIVE: Our objective was to gain insight on the role of gastrointestinal hormones on poor WL maintenance (P-WLM) following RYGB. DESIGN AND PATIENTS: First, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin responses to a standardized mixed liquid meal (SMLM) were compared between subjects with good WL (G-WL, n = 32) or P-WLM (n = 22). Second, we evaluated food intake (FI) following blockade of gut hormonal secretion in G-WL (n = 23) or P-WLM (n = 19) subjects. Finally, the impact of dietary-induced WL on the hormonal response in subjects with P-WLM (n = 14) was assessed. SETTING: This study was undertaken in a tertiary hospital. MAIN OUTCOME MEASURES: In studies 1 and 3, the outcomes measures were the areas under the curve of gut hormones following a SMLM; in study 2, FI following subcutaneous injection of saline or octreotide were evaluated. RESULTS: P-WLM associated a blunted GLP-1 (P = .044) and PYY (P = .001) responses and lesser suppression of ghrelin (P = .032) following the SMLM challenge. On saline day, FI in the G-WL (393 ± 143 kcal) group was less than in the P-WLM (519 ± 143 Kcal; P = .014) group. Octreotide injection resulted in enlarged FI in both groups (G-WL: 579 ± 248 kcal, P = .014; P-WLM: 798 ± 284 Kcal, P = .036), but the difference in FI between groups remained (P < .001). In subjects with P-WLM, dietary-induced WL resulted in larger ghrelin suppression (P = .046), but no change in the GLP-1 or PYY responses. CONCLUSION: Our data show gastrointestinal hormones play a role in the control of FI following RYGB, but do not support that changes in GLP-1, PYY, or ghrelin play a major role as determinants of P-WLM after this type of surgery.

Longitudinal changes of blood pressure after weight loss: factors involved.

BACKGROUND: The combination of obesity and hypertension (HT) places patients at a higher risk for adverse cardiovascular outcomes and raises the need to establish the pathogenic mechanisms of this relationship. The aim of this study was to assess the effects of important weight loss on longitudinal changes in blood pressure (BP) and investigate the pathogenic factors associated with these changes. METHODS: We performed a prospective, open-label study including 37 obese hypertensive patients (28 females, mean age 52±8 yr) undergoing BS. Before BS, and at 4 and 12 months postoperatively, the body mass index (BMI), 24-h ambulatory BP, renin-angiotensin-aldosterone system (RAAS: plasma rennin activity, aldosterone, angiotensin II, and angiotensin converting enzyme), sympathetic nervous system (SNS: metanephrines, normetanephrines, and norepinephrine) components, leptin, insulin, and abdominal fat were measured. RESULTS: Before BS, HT-duration was 6±6 years, the BMI 45±5 kg/m2 and excess weight (EBW) was 53±12 kg. At 12 months, the excess BMI loss was 14 kg/m2 and the EBW loss was 70 %; HT remission was observed in 70%; 24-h (systolic 19±13/diastolic 7±9 mm Hg), day and night BP levels and aldosterone, norepinephrine, leptin, insulin, subcutaneous and visceral abdominal fat (VAT) significantly decreased (P<.05). Mixed models for repeated measures revealed that HT-duration, baseline BP, BMI, and VAT area were the main variables associated with longitudinal changes in BP. CONCLUSION: These results demonstrate that the hypotensive response after weight loss in severely hypertensive obese patients is mainly regulated by HT-duration, baseline BP, BMI and VAT area, independently of suppression of hyperinsulinemia or changes in RAAS and SNS components.

Long-term effects of sleeve gastrectomy and Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus in morbidly obese subjects.

OBJECTIVE: To identify the rates and the predictors of long-term remission and the recurrence of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP) or sleeve gastrectomy (SG). BACKGROUND: The durability of the improvement of T2DM after bariatric surgery is not well characterized. METHODS: One hundred fifty-three subjects with T2DM (RYGBP: n = 98; SG: n = 55) were evaluated for remission and recurrence of the disease throughout 35.4 ± 13.5 months' follow-up. The type of surgery, demographic, anthropometric, and biochemical parameters were ascertained as predictors of T2DM outcomes. Glucagon-like peptide 1 (GLP-1) responses after a standard mixed liquid meal were compared between patients presenting with T2DM remission after RYGBP or SG. RESULTS: 75.2% of subjects presented with remission of T2DM lasting at least 12 months. However, in 12.1% of subjects, T2DM recurred. Regression analysis showed a longer duration of T2DM (P = 0.006), a higher presurgical glycated hemoglobin level (P = 0.019), insulin treatment at baseline (P = 0.001), and a lower excess weight loss at last follow-up visit (P < 0.001) as independent predictors for the lack of T2DM remission. Insulin use before surgery (P = 0.005), an older age (P = 0.05), and weight regain after remission (P = 0.021) predicted recurrence of the disease. Long-term remission of T2DM after SG or RYGBP was associated with a comparably enlarged GLP-1 response to a standard mixed liquid meal challenge. CONCLUSIONS: Roux-en-Y gastric bypass and SG are associated with comparable remission rates of T2DM. However, insufficient weight loss or weight regain in those with a more advanced disease may hamper the benefits of these surgical techniques on T2DM.