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1.
Diabetes Obes Metab ; 26(3): 1023-1032, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38092710

RESUMEN

AIM: To assess weight loss associated with liraglutide 3.0 mg treatment in individuals with obesity (body mass index [BMI] ≥30 kg/m2 ) or overweight (BMI > 27 to <30 kg/m2 ) in a reimbursed, real-world setting in Switzerland. MATERIALS AND METHODS: ADDRESS was a non-comparative, multicentre, retrospective exposure cohort study in Switzerland, examining weight loss in individuals with obesity or overweight whose treatment was reimbursed (divided into BMI subgroups) or non-reimbursed. The primary outcomes were proportions of participants in the reimbursed cohort achieving predefined weight loss targets with liraglutide 3.0 mg at Week 16 (≥5% and ≥7% for the lower BMI [28 to <35 kg/m2 with weight-related comorbidities] and higher BMI [≥35 kg/m2 ] subgroups, respectively) and Month 10 (additional ≥5% from Week 16; per Swiss reimbursement criteria). RESULTS: The full analysis set comprised 258 individuals (195 reimbursed; 63 non-reimbursed). In the reimbursed cohort, 139 individuals (71.3%) achieved their weight loss targets at Week 16. Of individuals who met the Week-16 criteria, 43.2% attained an additional 5% weight loss at Month 10. In 162 individuals for whom data were recorded at Month 10, the mean (standard deviation) relative weight loss from baseline to Month 10 was -12.4% (6.4%). CONCLUSIONS: Although reimbursement criteria may be difficult to achieve, particularly the additional weight loss of 5% from Week 16 to Month 10, a clinically relevant overall weight loss from baseline to Month 10 was shown in most individuals with obesity or overweight who received liraglutide 3.0 mg.


Asunto(s)
Liraglutida , Sobrepeso , Adulto , Humanos , Liraglutida/uso terapéutico , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Sobrepeso/epidemiología , Suiza/epidemiología , Estudios Retrospectivos , Estudios de Cohortes , Obesidad/tratamiento farmacológico , Obesidad/epidemiología , Pérdida de Peso
2.
Ther Umsch ; 80(6): 280-283, 2023 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-37855532

RESUMEN

INTRODUCTION: Endocrinological or metabolic disorders often affect a wide variety of functions of the organism. This can also include an impairment of respiratory function. Diabetic ketoacidosis as a result of insulin deficiency is a typical metabolic acidosis, which the body tries to compensate by an increased exhalation of carbon dioxide. This leads to the classic picture of "Kussmaul" breathing. Due to the increased use of SGLT2 inhibitors, which can reduce the otherwise typical hyperglycemia and thus complicate diagnosis, the occurrence of diabetic ketoacidosis has remained an important differential diagnosis in recent years. Pathologies of the thyroid gland can lead to dyspnea not only by morphological changes, for example in the case of goiter (compression). Functional disorders must also be considered here. Both hypo- and hyperthyroidism affect the cardiovascular system in different ways and may ultimately lead to the clinical picture of dyspnea. If the corresponding entities are thought of, the laboratory diagnosis of the aforementioned metabolic/endocrinological disorders is then basically straightforward. Accordingly, knowledge of these disorders as a differential diagnosis of tachy- and dyspnea is important.


Asunto(s)
Acidosis , Cetoacidosis Diabética , Hiperglucemia , Humanos , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/terapia , Cetoacidosis Diabética/complicaciones , Acidosis/complicaciones , Acidosis/diagnóstico , Hiperglucemia/complicaciones , Insulina , Disnea/diagnóstico , Disnea/etiología
3.
Horm Metab Res ; 54(8): 522-531, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35468630

RESUMEN

Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship between COVID-19 and liver function/liver diseases. Additionally, we present the most frequent histologic findings as well as the most important direct and indirect mechanisms supporting a COVID-19 mediated liver injury. Furthermore, we focus on the most frequent liver disease in the general population, non-alcoholic or metabolic-associated fatty liver disease (NAFLD/MAFLD), and describe how COVID-19 may affect NAFLD/MAFLD development and progression and conversely how NAFLD/MAFLD may further aggravate a COVID-19 infection. Finally, we present the long-term consequences of the pandemic on the development and management of NAFLD.


Asunto(s)
COVID-19 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Pandemias , Factores de Riesgo
4.
J Hepatol ; 75(1): 46-54, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33684506

RESUMEN

BACKGROUND & AIMS: Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on lipid metabolism independently of excessive caloric intake. METHODS: A total of 94 healthy men were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSBs) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80 g/day) in addition to their usual diet or SSB abstinence (control group) for 7 weeks. De novo fatty acid (FA) and triglyceride synthesis, lipolysis and plasma free FA (FFA) oxidation were assessed by tracer methodology. RESULTS: Daily intake of beverages sweetened with free fructose and fructose combined with glucose (sucrose) led to a 2-fold increase in basal hepatic fractional secretion rates (FSR) compared to control (median FSR %/day: sucrose 20.8 (p = 0.0015); fructose 19.7 (p = 0.013); control 9.1). Conversely, the same amounts of glucose did not change FSR (median of FSR %/day 11.0 (n.s.)). Fructose intake did not change basal secretion of newly synthesized VLDL-triglyceride, nor did it alter rates of peripheral lipolysis, nor total FA and plasma FFA oxidation. Total energy intake was similar across groups. CONCLUSIONS: Regular consumption of both fructose- and sucrose-sweetened beverages in moderate doses - associated with stable caloric intake - increases hepatic FA synthesis even in a basal state; this effect is not observed after glucose consumption. These findings provide evidence of an adaptative response to regular fructose exposure in the liver. LAY SUMMARY: This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health. CLINICAL TRIAL REGISTRATION NUMBER: NCT01733563.


Asunto(s)
Ácidos Grasos/biosíntesis , Fructosa , Glucosa , Lipogénesis , Lipoproteínas VLDL/biosíntesis , Hígado , Sacarosa , Triglicéridos/biosíntesis , Adulto , Método Doble Ciego , Ingestión de Energía , Fructosa/administración & dosificación , Fructosa/efectos adversos , Fructosa/metabolismo , Glucosa/administración & dosificación , Glucosa/metabolismo , Voluntarios Sanos , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/fisiología , Lipogénesis/efectos de los fármacos , Lipogénesis/fisiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Sacarosa/administración & dosificación , Sacarosa/efectos adversos , Sacarosa/metabolismo , Bebidas Azucaradas , Edulcorantes/farmacología
5.
Anal Chem ; 93(2): 1170-1178, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33315383

RESUMEN

Methanol poisoning outbreaks after consumption of adulterated alcohol frequently overwhelm health care facilities in developing countries. Here, we present how a recently developed low-cost and handheld breath detector can serve as a noninvasive and rapid diagnostic tool for methanol poisoning. The detector combines a separation column and a micromachined chemoresistive gas sensor fully integrated into a device that communicates wirelessly with a smartphone. The performance of the detector is validated with methanol-spiked breath of 20 volunteers (105 breath samples) after consumption of alcoholic beverages. Breath methanol concentrations were quantified accurately within 2 min in the full breath-relevant range (10-1000 ppm) in excellent agreement (R2 = 0.966) with benchtop mass spectrometry. Bland-Altman analysis revealed sufficient limits of agreement (95% confidence intervals), promising to indicate reliably the clinical need for antidote and hemodialysis treatment. This simple-in-use detector features high diagnostic capability for accurate measurement of methanol in spiked breath, promising for rapid screening of methanol poisoning and assessment of severity. It can be applied readily by first responders to distinguish methanol from ethanol poisoning and monitor in real time the subsequent hospital treatment.


Asunto(s)
Pruebas Respiratorias , Metanol/análisis , Humanos , Espectroscopía Infrarroja por Transformada de Fourier
6.
Clin Transplant ; 35(3): e14197, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33340422

RESUMEN

BACKGROUND: Obesity adversely affects wait-listing and precludes patients with concomitant end-stage renal disease and type 1 diabetes mellitus from getting a simultaneous pancreas and kidney transplantation (SPK). OBJECTIVE: To analyze safety and efficacy of laparoscopic sleeve gastrectomy (LSG) before SPK in severely obese type I diabetics. METHODS: We assessed weight curve, complications, and graft function of three patients who underwent LSG before SPK. RESULTS: LSG was uneventful in all patients. Body mass index dropped from 38.4 (range 35.7 - 39.9) before LSG to 28.5 (26.8 - 30.9) until SPK, with a mean loss of 25.8% (22.4 - 32.3). Interval between LSG and SPK was 364.3 (173 - 587) days. Pancreas and kidney graft function was excellent, with 100% insulin-free and dialysis-free survival over a mean follow-up of 3.6 (2.9 - 4.5) years. A1C dropped from 7% (6.3 - 8.2) before LSG to 4.9% (4.7 - 5.3) and 4.8% (4.5 - 5.1) 1 and 2 years after SPK, respectively. CONCLUSION: LSG before SPK is safe and effective to enable severely obese type I diabetics to receive a lifesaving transplant. This is the first study analyzing the role of bariatric surgery before simultaneous pancreas and kidney transplantation.


Asunto(s)
Trasplante de Riñón , Laparoscopía , Obesidad Mórbida , Trasplante de Páncreas , Gastrectomía , Supervivencia de Injerto , Humanos , Obesidad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Páncreas , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de Peso
7.
Clin Transplant ; 32(1)2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29140547

RESUMEN

The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas retransplantation. Ten patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months. The primary end point of HbA1c <7.0% and freedom of severe hypoglycemia was met by nine of 10 patients after follow-up after islet transplantation and in all three patients in the pancreas retransplantation group, but by none of the patients in the group without retransplantation (n = 7). Insulin requirement was reduced by 50% after islet transplantation. Kidney function (eGFR) declined with a rate of -1.0 mL ± 1.2 mL/min/1.73 m2 per year during follow-up after islet transplantation, which tended to be slower than in the group without retransplantation (P = .07). Islet transplantation after deceased donor pancreas transplant failure is a method that can safely improve glycemic control and reduce the incidence of severe hypoglycemia and thus establish similar glycemic control as after initial pancreas transplantation, despite the need of additional exogenous insulin.


Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Rechazo de Injerto/prevención & control , Hipoglucemia/prevención & control , Trasplante de Islotes Pancreáticos/métodos , Trasplante de Páncreas/efectos adversos , Complicaciones Posoperatorias , Adolescente , Glucemia/metabolismo , Niño , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Hipoglucemia/etiología , Masculino , Pronóstico , Factores de Riesgo , Donantes de Tejidos
8.
Sensors (Basel) ; 18(11)2018 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-30373291

RESUMEN

Ketogenic diet (KD; high fat, low carb) is a standard treatment for obesity, neurological diseases (e.g., refractory epilepsy) and a promising method for athletes to improve their endurance performance. Therein, the level of ketosis must be regulated tightly to ensure an effective therapy. Here, we introduce a compact and inexpensive breath sensor to monitor ketosis online and non-invasively. The sensor consists of Si-doped WO3 nanoparticles that detect breath acetone selectively with non-linear response characteristics in the relevant range of 1 to 66 ppm, as identified by mass spectrometry. When tested on eleven subjects (five women and six men) undergoing a 36-h KD based on the Johns Hopkins protocol, this sensor clearly recognizes the onset and progression of ketosis. This is in good agreement to capillary blood ß-hydroxybutyrate (BOHB) measurements. Despite similar dieting conditions, strong inter-subject differences in ketosis dynamics were observed and correctly identified by the sensor. These even included breath acetone patterns that could be linked to low tolerance to that diet. As a result, this portable breath sensor represents an easily applicable and reliable technology to monitor KD, possibly during medical treatment of epilepsy and weight loss.


Asunto(s)
Acetona/análisis , Pruebas Respiratorias/instrumentación , Dieta Cetogénica , Calibración , Estudios de Cohortes , Femenino , Humanos , Cetosis/sangre , Cetosis/diagnóstico , Masculino , Adulto Joven
9.
Curr Opin Cardiol ; 32(4): 454-459, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28426445

RESUMEN

PURPOSE OF REVIEW: In this review, we summarize the latest findings on small, dense LDL (sdLDL) atherogenic particles, including their associations with other biomarkers. RECENT FINDINGS: Increased sdLDL levels have been reported not only in different metabolic disorders such as diabetes, obesity and metabolic syndrome, but also in patients with rheumatoid and psoriatic arthritis as well as hypothyroidism. A wide range of lipid-lowering, as well as other drug classes, including novel antidiabetic agents and nutraceuticals, exert favourable effects on these atherogenic particles. The 'gold standard' methodology for the assessment of sdLDL has not been established yet. However, the association between sdLDL and several biomarkers could facilitate their assessment. SUMMARY: Estimation of sdLDL in daily clinical practice may help with the identification of patients at high cardiovascular risk and further contribute in directing specific interventions to prevent and/or decrease such risk.


Asunto(s)
Aterosclerosis/etiología , LDL-Colesterol/sangre , Síndrome Metabólico/complicaciones , Aterosclerosis/metabolismo , Biomarcadores/sangre , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Humanos , Síndrome Metabólico/sangre , Tamaño de la Partícula , Factores de Riesgo
10.
Ann Nutr Metab ; 71(3-4): 129-135, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28848183

RESUMEN

BACKGROUND: Adult phenylketonuria (PKU) patients often reduce their intake of amino acid mixture (AAM) to less than the prescribed amounts. Effects of reduced AAM intake on nutrient supply were evaluated. METHODS: Nutrient intake was calculated in 20 adult PKU patients based on a structured food record and complemented by laboratory assessment of nutritional status. Patients were classified into 2 groups, (A) regular AAM intake, or (B) AAM intake below calculated requirements. RESULTS: Group B consumed a higher proportion of natural protein (60 ± 23 vs. 33 ± 12%, p = 0.002); however, the total protein intake was below the recommended amounts in 60% of patients in group B versus 7% in group A (p = 0.03). Fat intake was higher in group B (39 ± 9% of energy vs. 31 ± 6%, p = 0.03), mainly from saturated fats. Selenium, folate, and vitamin B12 intake was below the recommended intake in group B. However, serum concentrations of these analytes remained within the normal range in both groups, although vitamin B12 levels were lower in group B. Plasma tyrosine correlated with AAM intake, and hydroxyproline correlated with the amount of natural protein consumed. CONCLUSION: Relaxed AAM intake resulted in insufficient nutrient supply, despite a compensatory increase in consumption of natural protein. Care needs to be taken to ensure adequate nutrition in adults with PKU.


Asunto(s)
Aminoácidos/administración & dosificación , Nutrientes/análisis , Estado Nutricional , Fenilcetonurias/dietoterapia , Adolescente , Adulto , Estudios Transversales , Dieta , Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Selenio/sangre , Vitamina B 12/sangre , Adulto Joven
12.
Diabetologia ; 57(8): 1635-44, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24865615

RESUMEN

AIMS/HYPOTHESIS: Hypoxic damage complicates islet isolation for transplantation and may contribute to beta cell failure in type 2 diabetes. Polymorphisms in the SLC30A8 gene, encoding the secretory granule zinc transporter 8 (ZnT8), influence type 2 diabetes risk, conceivably by modulating cytosolic Zn(2+) levels. We have therefore explored the role of ZnT8 and cytosolic Zn(2+) in the response to hypoxia of pancreatic islet cells. METHODS: Human, mouse or rat islets were isolated and exposed to varying O2 tensions. Cytosolic free zinc was measured using the adenovirally expressed recombinant targeted zinc probe eCALWY4. Gene expression was measured using quantitative (q)RT-PCR, western (immuno-) blotting or immunocytochemistry. Beta cells were identified by insulin immunoreactivity. RESULTS: Deprivation of O2 (1% vs 5% or 21%) for 24 h lowered free cytosolic Zn(2+) concentrations by ~40% (p < 0.05) and ~30% (p < 0.05) in mouse and human islet cells, respectively. Hypoxia similarly decreased SLC30A8 mRNA expression in islets, and immunoreactivity in beta cells. Implicating lowered ZnT8 levels in the hypoxia-induced fall in cytosolic Zn(2+), genetic ablation of Slc30a8 from mouse islets lowered cytosolic Zn(2+) by ~40% (p < 0.05) and decreased the induction of metallothionein (Mt1, Mt2) genes. Cell survival in the face of hypoxia was enhanced in small islets of older (>12 weeks) Slc30a8 null mice vs controls, but not younger animals. CONCLUSIONS/INTERPRETATION: The response of pancreatic beta cells to hypoxia is characterised by decreased SLC30A8 expression and lowered cytosolic Zn(2+) concentrations. The dependence on ZnT8 of hypoxia-induced changes in cell survival may contribute to the actions of SLC30A8 variants on diabetes risk in humans.


Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Hipoxia/metabolismo , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Zinc/metabolismo , Animales , Proteínas de Transporte de Catión/genética , Citosol/metabolismo , Humanos , Metalotioneína/genética , Metalotioneína/metabolismo , Ratones , Ratas , Transportador 8 de Zinc
13.
EClinicalMedicine ; 73: 102661, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38846069

RESUMEN

Background: The benefit of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) in weight reduction against potential harms remains unclear. This study aimed at evaluating the benefit-harm balance of initiating GLP-1 RAs versus placebo for weight loss in people living with overweight and obesity but without diabetes. Methods: We performed benefit-harm balance modelling, which will be updated as new evidence emerges. We searched for randomised controlled trials (RCTs) in PubMed, controlled trials registry, drug approval and regulatory documents, and outcome preference weights as of April 10, 2024. We synthesize data using pairwise meta-analysis to estimate the effect of GLP-1 RAs to inform the benefit-harm balance modelling. We predicted the absolute effects of the positive and negative outcomes over 1 and 2 years of treatment using exponential models. We applied preference weights to the outcomes, ranging from 0 for least concerning to 1.0 for most concerning. We then calculated whether the benefit of achieving 5% and 10% weight loss outweighed the harms on a common scale. The analyses accounted for the statistical uncertainties of treatment effects, preference weights, and outcome risks. Findings: We included 8 RCTs involving 8847 participants. The pooled average age was 46.7 years, with the majority being women (74%) and people living with obesity (96%). Of 1000 persons treated with GLP-1 RAs for 2 years, 375 (95% confidence interval 352 to 399) achieved a 10% weight loss, and 318 (296 to 339) achieved a 5% weight loss compared to those treated with placebo. Several harm outcomes were more frequent in the GLP-1 RA group, including 41 abdominal pain events per 1000 persons over 2 years (19 to 69), cholelithiasis (8, 1 to 21), constipation (118, 78 to 164), diarrhoea (100, 42 to 173), alopecia (57, 10 to 176), hypoglycaemia (17, 1 to 68), injection site reactions (4, -3 to 19), and vomiting (110, 80 to 145) among others. Achieving a 10% weight loss with GLP-1 RA therapy outweighed the cumulative harms, with a net benefit probability of 0.97 at year 1 and 0.91 at year 2. The absolute net benefit was equivalent to 104 (100 to 112) per 1000 persons achieving a 10% weight loss over 2 years without experiencing any worrisome harm. A 5% weight loss did not show a net benefit, with probabilities of 0.13 and 0.01 at year 1 and year 2, respectively. However, these benefits were sensitive to preference weights, suggesting that even a 5% weight loss could be net beneficial for individuals with less concern about harm outcomes. The net benefit for a 10% weight loss was highest for semaglutide, followed by liraglutide and tirzepatide, with 2-year probabilities of 0.96, 0.72, and 0.60, respectively. Interpretation: The benefit of GLP-1 RAs exceeded the harms for weight loss in the first 2 years of treatment, yet the net benefit was dependent on individual' treatment goals (10% or 5% weight loss) and willingness to accept harms in pursuit of weight loss. This implies that treatment decisions have to be personalized to individuals to optimize benefits and reduce harms and overuse of treatments. Due to varying evidence, especially regarding harm outcomes across studies, it is necessary to continuously update and monitor the benefit-harm balance of GLP-1 RAs. Funding: SNSF and LOOP Zurich.

14.
Cardiovasc Res ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739545

RESUMEN

BACKGROUND: Obesity and type 2 diabetes (T2D) are major risk factors for cardiovascular diseases (CVD). Dysregulated pro-apoptotic ceramide synthesis reduces ß-cell insulin secretion, thereby promoting hyperglycemic states which may manifest as T2D. Pro-apoptotic ceramides modulate insulin sensitivity and glucose tolerance while being linked to poor cardiovascular outcomes. Sirtuin-1 (SIRT1) is a NAD + - dependent deacetylase that protects against pancreatic ß-cell dysfunction; however, systemic levels are decreased in obese T2D mice and may promote pro-apoptotic ceramide synthesis and hyperglycemia. Herein, we aimed to assess the effects of restoring circulating SIRT1 levels to prevent metabolic imbalance in obese and diabetic mice. METHODS AND RESULTS: Circulating SIRT1 levels were reduced in obese diabetic mice (db/db) as compared to age-matched non-diabetic db/+ controls. Restoration of SIRT1 plasma levels with recombinant murine SIRT1 for 4-weeks prevented body weight gain, improved glucose tolerance, insulin sensitivity and vascular function in mice models of obesity and T2D. Untargeted lipidomics revealed that SIRT1 restored insulin-secretory function of ß-cells by reducing synthesis and accumulation of pro-apoptotic ceramides. Molecular mechanisms involved direct binding to and deacetylation of Toll-like receptor 4 (TLR4) by SIRT1 in ß-cells thereby decreasing the rate limiting enzymes of sphingolipid synthesis SPTLC1/2 via AKT/NF-κB. Among T2D patients, those with high baseline plasma levels of SIRT1 prior to metabolic surgery displayed restored ß-cell function (HOMA2- ß) and were more likely to have T2D remission during follow-up. CONCLUSION: Acetylation of TLR4 promotes ß-cell dysfunction via ceramide synthesis in T2D, which is blunted by systemic SIRT1 replenishment. Hence, restoration of systemic SIRT1 may provide a novel therapeutic strategy to counteract toxic ceramide synthesis and mitigate cardiovascular complications of T2D.

15.
J Endocrinol ; 257(2)2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36753292

RESUMEN

Despite the existence of numerous studies supporting a pathological link between fructose consumption and the development of the metabolic syndrome and its sequelae, such as non-alcoholic fatty liver disease (NAFLD), this link remains a contentious issue. With this article, we shed a light on the impact of sugar/fructose intake on hepatic de novo lipogenesis (DNL), an outcome parameter known to be dysregulated in subjects with type 2 diabetes and/or NAFLD. In this review, we present findings from human intervention studies using physiological doses of sugar as well as mechanistic animal studies. There is evidence from both human and animal studies that fructose is a more potent inducer of hepatic lipogenesis than glucose. This is most likely due to the liver's prominent physiological role in fructose metabolism, which may be disrupted under pathological conditions by increased hepatic expression of fructolytic and lipogenic enzymes. Increased DNL may not only contribute to ectopic fat deposition (i.e. in the liver), but it may also impair several metabolic processes through DNL-related fatty acids (e.g. beta-cell function, insulin secretion, or insulin sensitivity).


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fructosa/efectos adversos , Lipogénesis/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Hígado/metabolismo
16.
Clin Obes ; 13(1): e12561, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36239531

RESUMEN

Previous data from short term studies have shown an efficacy of the duodenal-jejunal bypass liner (DJBL) for weight loss. However, less data is available regarding weight change after device removal and possible predictors for weight loss. This is a retrospective chart review of all patients who had DJBL inserted at the University Hospital Zurich between December 2012 and June 2015. A total of 27 patients had DJBL insertion. The median BMI at baseline was 38.5 (34.0-42.2) kg/m2 . In the 24 patients with DJBL treatment >3 months (failed implantation or early removal due to side effects in 3 patients), the mean duration of implantation was 42.9 ± 13.1 weeks. During the treatment, the mean total body weight loss (%TBWL) was 15.0 ± 8.3%. Fifteen patients had long-term follow-up data available (mean duration of follow-up 4.0 ± 0.9 years). The mean weight change was 12.7 ± 12.8 kg, corresponding with a mean % weight regain of 13.3 ± 13.3%. Five patients (33.3%) subsequently underwent bariatric surgery. In patients with class I obesity (BMI <35 kg/m2 at baseline), 4 out of 6 (66.7%) had a stable weight or only a weight regain <7%. In contrast, no patient with BMI >35 kg/m2 at baseline was able to keep weight regain below 7%. DJBL is an effective treatment for obesity, but substantial weight regain occurs during long-term follow up after the device removal, in particular in patients with BMI > 35 kg/m2 .


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Obesidad Mórbida , Humanos , Duodeno/cirugía , Yeyuno/cirugía , Índice de Masa Corporal , Estudios Retrospectivos , Estudios de Seguimiento , Obesidad Mórbida/cirugía , Diabetes Mellitus Tipo 2/cirugía , Estudios Prospectivos , Obesidad/etiología , Resultado del Tratamiento , Cirugía Bariátrica/efectos adversos , Pérdida de Peso , Aumento de Peso
17.
Obes Facts ; 16(4): 381-391, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36977399

RESUMEN

INTRODUCTION: Weight bias refers to negative attitudes toward individuals because of their weight. Evidence-based strategies to successfully reduce weight bias in medical students are lacking. The purpose of this study was to investigate the impact of a multifaceted intervention on medical students' attitudes toward patients with obesity. METHODS: Third and fourth year medical students (n = 79), who enrolled in an 8-week graduate course focusing on the various epidemiologic, physiological, and clinical aspects of obesity, including a gamification task with bariatric weight suits (BWSs), were asked to complete the Nutrition, Exercise and Weight Management (NEW) Attitudes Scale questionnaire pre- and post-course. The inclusion period was between September 2018 and June 2021 and covered 4 consecutive groups of students. RESULTS: The overall NEW Attitudes Scale scores did not change significantly pre- versus post-intervention (pre-course: 19.59, post-course: 24.21, p value = 0.24). However, the subgroup of 4th year medical students showed a significant improvement in their attitudes (pre-course: 16.4, post-course: 26.16, p value = 0.02). The Thurstone rating of 9 out of 31 individual survey items changed significantly from pre- to post-course with a moderate strength (Cramer's V >0.2), including 5 items showing weight bias reduction. The disagreement with the statement "overweight/obese individuals lack willpower" increased from 37 to 68%. CONCLUSION: These findings suggest that in medical students with a low level of weight bias at baseline, a semester course on obesity combined with BWS use affects only a limited number of items of the NEW Attitudes Scale questionnaire. The sensitization of medical students to weight stigma has the potential to improve quality of healthcare for patients with obesity.


Asunto(s)
Bariatria , Estudiantes de Medicina , Prejuicio de Peso , Humanos , Actitud del Personal de Salud , Obesidad/terapia , Encuestas y Cuestionarios
18.
Sens Diagn ; 2(4): 918-928, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37465007

RESUMEN

Non-invasive breath analysis with mobile health devices bears tremendous potential to guide therapeutic treatment and personalize lifestyle changes. Of particular interest is the breath volatile acetone, a biomarker for fat burning, that could help in understanding and treating metabolic diseases. Here, we report a hand-held (6 × 10 × 19.5 cm3), light-weight (490 g), and simple device for rapid acetone detection in breath. It comprises a tailor-made end-tidal breath sampling unit, connected to a sensor and a pump for on-demand breath sampling, all operated using a Raspberry Pi microcontroller connected with a HDMI touchscreen. Accurate acetone detection is enabled by introducing a catalytic filter and a separation column, which remove and separate undesired interferents from acetone upstream of the sensor. This way, acetone is detected selectively even in complex gas mixtures containing highly concentrated interferents. This device accurately tracks breath acetone concentrations in the exhaled breath of five volunteers during a ketogenic diet, being as high as 26.3 ppm. Most importantly, it can differentiate small acetone changes during a baseline visit as well as before and after an exercise stimulus, being as low as 0.5 ppm. It is stable for at least four months (122 days), and features excellent bias and precision of 0.03 and 0.6 ppm at concentrations below 5 ppm, as validated by proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS). Hence, this detector is highly promising for simple-in-use, non-invasive, and routine monitoring of acetone to guide therapeutic treatment and track lifestyle changes.

19.
Front Nutr ; 10: 1255499, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37810925

RESUMEN

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland-Altman plots, paired difference tests, and Pearson's correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = -329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = -543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p < 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).

20.
Diabetes Technol Ther ; 25(7): 467-475, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37093196

RESUMEN

Aims: To investigate the effect of empagliflozin on glucose dynamics in individuals suffering from postbariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). Methods: Twenty-two adults with PBH after RYGB were randomized to empagliflozin 25 mg or placebo once daily over 20 days in a randomized, double-blind, placebo-controlled, crossover trial. The primary efficacy outcome was the amplitude of plasma glucose excursion (peak to nadir) during a mixed-meal tolerance test (MMTT). Outcomes of the outpatient period were assessed using continuous glucose monitoring (CGM) and an event-tracking app. Results: The amplitude of glucose excursion during the MMTT was 8.1 ± 2.4 mmol/L with empagliflozin versus 8.1 ± 2.6 mmol/L with placebo (mean ± standard deviation, P = 0.807). CGM-based mean amplitude of glucose excursion during the 20-day period was lower with empagliflozin than placebo (4.8 ± 1.3 vs. 5.2 ± 1.6. P = 0.028). Empagliflozin reduced the time spent with CGM values >10.0 mmol/L (3.8 ± 3.5% vs. 4.7 ± 3.8%, P = 0.009), but not the time spent with CGM values <3.0 mmol/L (1.7 ± 1.6% vs. 1.5 ± 1.5%, P = 0.457). No significant difference was observed in the quantity and quality of recorded symptoms. Eleven adverse events occurred with empagliflozin (three drug-related) and six with placebo. Conclusions: Empagliflozin 25 mg reduces glucose excursions but not hypoglycemia in individuals with PBH. Clinical Trial Registration: Clinicaltrials.gov: NCT05057819.


Asunto(s)
Derivación Gástrica , Hipoglucemia , Adulto , Humanos , Derivación Gástrica/efectos adversos , Glucemia , Automonitorización de la Glucosa Sanguínea , Estudios Cruzados , Hipoglucemia/tratamiento farmacológico , Hipoglucemia/etiología , Hipoglucemia/prevención & control , Glucosa , Método Doble Ciego
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