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1.
Eur Thyroid J ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38718824

RESUMO

Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D) and weight gain. Transcranial biopsy is necessary, to define diagnosis and guide treatment decisions, but is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was done through thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose avidity on positron emission tomography/-computed tomography (FDG-PET/-CT), and volume increase during follow-up.

2.
Rev Med Suisse ; 20(859): 247-251, 2024 Jan 31.
Artigo em Francês | MEDLINE | ID: mdl-38299955

RESUMO

Gestational diabetes (GDM) is becoming increasingly common as a result of the increase in overweight, obesity and maternal age among pregnant women. As a result, in order to provide early hygienic and dietary management, it is recommended that targeted screening be carried out in the first trimester of pregnancy, based on the identification of risk factors in women. In the absence of risk factors, screening for gestational diabetes should be carried out for all pregnant women between 24 and 28 weeks' gestation. During pregnancy, the safest pharmacological treatment remains insulin, and the term of delivery should take account of additional risk factors, insulin requirements, fœtal growth kinetics and the balance of GDM. In the longer term, gestational diabetes should be regarded as a metabolic and cardiovascular warning sign.


Dû à l'augmentation du surpoids, de l'obésité et de l'âge maternel chez les femmes enceintes, le diabète gestationnel (DG) est de plus en plus fréquent. De ce fait, afin d'offrir une prise en charge hygiénodiététique précoce, il est recommandé d'effectuer un dépistage ciblé au premier trimestre de la grossesse pour identifier les facteurs de risque. En leur absence, le dépistage du DG doit être réalisé chez toutes les femmes enceintes entre 24 et 28 SA. Au cours de la grossesse, le traitement pharmacologique le plus sécuritaire reste l'insuline et le terme d'accouchement doit tenir compte des facteurs de risque surajoutés, des besoins en insuline, de la cinétique de croissance fœtale et de l'équilibre du DG. À plus long terme, le DG doit être considéré comme une alerte métabolique et cardiovasculaire.


Assuntos
Diabetes Gestacional , Ginecologia , Obstetrícia , Gravidez , Feminino , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Insulina , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/terapia
3.
Sci Adv ; 10(1): eadj4686, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38170783

RESUMO

Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency leading to hyperglycemia and several metabolic defects. Insulin therapy remains the cornerstone of T1DM management, yet it increases the risk of life-threatening hypoglycemia and the development of major comorbidities. Here, we report an insulin signaling-independent pathway able to improve glycemic control in T1DM rodents. Co-treatment with recombinant S100 calcium-binding protein A9 (S100A9) enabled increased adherence to glycemic targets with half as much insulin and without causing hypoglycemia. Mechanistically, we demonstrate that the hyperglycemia-suppressing action of S100A9 is due to a Toll-like receptor 4-dependent increase in glucose uptake in specific skeletal muscles (i.e., soleus and diaphragm). In addition, we found that T1DM mice have abnormal systemic inflammation, which is resolved by S100A9 therapy alone (or in combination with low insulin), hence uncovering a potent anti-inflammatory action of S100A9 in T1DM. In summary, our findings reveal the S100A9-TLR4 skeletal muscle axis as a promising therapeutic target for improving T1DM treatment.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Animais , Camundongos , Insulina/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemia/complicações , Hipoglicemia/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Calgranulina B
4.
Rev Med Suisse ; 20(856-7): 32-34, 2024 Jan 17.
Artigo em Francês | MEDLINE | ID: mdl-38231096

RESUMO

Diabetology is a continuously evolving discipline, many molecules are developed and treatment recommendations change often according to the latest published studies. It is therefore often difficult for the primary care physician to be up to date. After lifestyle measures that must always be preferred before any drug, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects. The purpose of this article is to guide the primary care physician to choose the most suitable pharmacological treatment for each patient, in the light of the 2023 novelties in the field of diabetes.


La diabétologie est une discipline en évolution continue, de nombreuses molécules sont développées et les recommandations de traitement changent fréquemment en fonction des dernières études publiées. Il est donc souvent difficile pour le médecin de premier recours d'être à jour. Après les mesures du style de vie qu'il faut toujours privilégier avant toute approche médicamenteuse, la metformine reste la base pharmacologique du traitement. Les recommandations actuelles préconisent d'instaurer un inhibiteur du SGLT2 ou un agoniste du récepteur du GLP-1 après la metformine car ces molécules ont montré des effets bénéfiques cardiovasculaires et rénaux. Le but de cet article est de fournir une aide au médecin de premier recours dans le choix du traitement pharmacologique le plus adapté à chaque patient, à la lumière des nouveautés 2023 dans le domaine du diabète.


Assuntos
Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Rim , Estilo de Vida , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
5.
Diabetes ; 73(1): 93-107, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37862465

RESUMO

In this study, we identified new lipid species associated with the loss of pancreatic ß-cells triggering diabetes. We performed lipidomics measurements on serum from prediabetic mice lacking ß-cell prohibitin-2 (a model of monogenic diabetes) patients without previous history of diabetes but scheduled for pancreaticoduodenectomy resulting in the acute reduction of their ß-cell mass (∼50%), and patients with type 2 diabetes (T2D). We found lysophosphatidylinositols (lysoPIs) were the main circulating lipid species altered in prediabetic mice. The changes were confirmed in the patients with acute reduction of their ß-cell mass and in those with T2D. Increased lysoPIs significantly correlated with HbA1c (reflecting glycemic control), fasting glycemia, and disposition index, and did not correlate with insulin resistance or obesity in human patients with T2D. INS-1E ß-cells as well as pancreatic islets isolated from nondiabetic mice and human donors exposed to exogenous lysoPIs showed potentiated glucose-stimulated and basal insulin secretion. Finally, addition of exogenous lysoPIs partially rescued impaired glucose-stimulated insulin secretion in islets from mice and humans in the diabetic state. Overall, lysoPIs appear to be lipid species upregulated in the prediabetic stage associated with the loss of ß-cells and that support the secretory function of the remaining ß-cells. ARTICLE HIGHLIGHTS: Circulating lysophosphatidylinositols (lysoPIs) are increased in situations associated with ß-cell loss in mice and humans such as (pre-)diabetes, and hemipancreatectomy. Pancreatic islets isolated from nondiabetic mice and human donors, as well as INS-1E ß-cells, exposed to exogenous lysoPIs exhibited potentiated glucose-stimulated and basal insulin secretion. Addition of exogenous lysoPIs partially rescued impaired glucose-stimulated insulin secretion in islets from mice and humans in the diabetic state. LysoPIs appear as lipid species being upregulated already in the prediabetic stage associated with the loss of ß-cells and supporting the function of the remaining ß-cells.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Estado Pré-Diabético , Humanos , Camundongos , Animais , Insulina , Lisofosfolipídeos , Glucose/farmacologia , Insulina Regular Humana
6.
Cell Rep Med ; 4(12): 101299, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38016481

RESUMO

Lipid homeostasis in humans follows a diurnal pattern in muscle and pancreatic islets, altered upon metabolic dysregulation. We employ tandem and liquid-chromatography mass spectrometry to investigate daily regulation of lipid metabolism in subcutaneous white adipose tissue (SAT) and serum of type 2 diabetic (T2D) and non-diabetic (ND) human volunteers (n = 12). Around 8% of ≈440 lipid metabolites exhibit diurnal rhythmicity in serum and SAT from ND and T2D subjects. The spectrum of rhythmic lipids differs between ND and T2D individuals, with the most substantial changes observed early morning, as confirmed by lipidomics in an independent cohort of ND and T2D subjects (n = 32) conducted at a single morning time point. Strikingly, metabolites identified as daily rhythmic in both serum and SAT from T2D subjects exhibit phase differences. Our study reveals massive temporal and tissue-specific alterations of human lipid homeostasis in T2D, providing essential clues for the development of lipid biomarkers in a temporal manner.


Assuntos
Diabetes Mellitus Tipo 2 , Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos/fisiologia , Gordura Subcutânea/metabolismo , Tecido Adiposo Branco/metabolismo , Lipídeos , Diabetes Mellitus Tipo 2/metabolismo
7.
Eur Thyroid J ; 12(6)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37855426

RESUMO

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/diagnóstico , Estudos Retrospectivos , Procedimentos Desnecessários , Nódulo da Glândula Tireoide/diagnóstico
8.
Diabetes Metab ; 49(5): 101470, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37657738

RESUMO

Glucagon-like peptide 1 (GLP-1) is a hormone of the incretin family, secreted in response to nutrient ingestion, and plays a role in metabolic homeostasis. GLP-1 receptor agonist has a peripheral and a central action, including stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. Through their mechanism, their use in the treatment of type 2 diabetes has been extended to the management of obesity, and numerous trials are being conducted to assess their cardiovascular effect. Type 2 diabetes appears to share common pathophysiological mechanisms with the development of cognitive disorders, such as Alzheimer's and Parkinson's disease, related to insulin resistance. In this review, we aim to examine the pathological features between type 2 diabetes and dementia, GLP-1 central effects, and analyze the relevant literature about the effect of GLP-1 analogs on cognitive function of patients with type 2 diabetes but also without. Results tends to show an improvement in some brain markers (e.g. hippocampal connections, cerebral glucose metabolism, hippocampal activation on functional magnetic resonance imaging), but without being able to demonstrate a strong correlation to cognitive scores. Some epidemiological studies suggest that GLP-1 receptor agonists may offer a protective effect, by delaying progression to dementia when diabetic patients are treated with GLP-1 receptor agonists. Ongoing trials are in progress and may provide disease-modifying care for Alzheimer's disease and Parkinson's disease patients in the future.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Doença de Parkinson , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insulina/metabolismo , Cognição
9.
Int J Mol Sci ; 24(14)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37511031

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become a widely studied subject due to its increasing prevalence and links to diseases such as type 2 diabetes and obesity. It has severe complications, including nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and portal hypertension that can lead to liver transplantation in some cases. To better prevent and treat this pathology, it is important to understand its underlying physiology. Here, we identify two main factors that play a crucial role in the pathophysiology of NAFLD: oxidative stress and the key role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). We discuss the pathophysiology linking these factors to NAFLD pathophysiology.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Humanos , Antígeno Carcinoembrionário , Molécula 1 de Adesão Celular , Diabetes Mellitus Tipo 2/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo
11.
Rev Med Suisse ; 19(829): 1080-1084, 2023 May 31.
Artigo em Francês | MEDLINE | ID: mdl-37260203

RESUMO

Diabetic foot syndrome is a common complication in people with diabetes and peripheral sensory impairment. This complex situation requires early clinical detection by various health care professionals, but also by patients and their relatives. The clinical course, the severity of the prognosis and the management will be determined by the speed of the diagnosis. In the case of confirmed disease, multidisciplinary management is necessary. The most important intervention, both for prevention and treatment, is the discharge of the affected foot.


Le syndrome du pied diabétique est une complication fréquente chez les personnes ayant un diabète et une atteinte de la sensibilité périphérique. Cette situation complexe nécessite une détection clinique précoce, par les divers professionnels de la santé mais aussi par les patients et leurs proches. L'évolution clinique, la gravité du pronostic et la prise en charge seront déterminées par la rapidité du diagnostic. En cas d'atteinte confirmée, une prise en charge multidisciplinaire est nécessaire. L'intervention la plus importante, tant pour la prévention que le traitement, est la décharge du pied atteint.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/diagnóstico , Pé Diabético/etiologia , Pé Diabético/terapia , Prognóstico , Diagnóstico Precoce , Síndrome
12.
Rev Med Suisse ; 19(829): 1090-1093, 2023 May 31.
Artigo em Francês | MEDLINE | ID: mdl-37260205

RESUMO

NAFLD, whose prevalence keeps growing, is strongly linked with type 2 diabetes (T2D) through insulin resistance and oxidative stress. A multifactorial association with T1D has recently been found. NAFLD screening aims to identify non-alcoholic steatohepatitis (NASH) and fibrosis and to better refer to liver specialists. It is recommended for patients at higher risk, such as those with T2D. NAFLD treatment cornerstone is weight loss, obtained through lifestyle interventions, obesity pharmacotherapy, and bariatric surgery. When treating patients suffering from NAFLD and T2D, we should prioritize GLP-1 analogues and PPAR agonists, capable of regressing NASH, and SGLT2i, efficient on liver steatosis.


La stéatopathie non alcoolique (NAFLD), dont la prévalence est à la hausse, est une pathologie fortement liée au diabète de type 2 (DT2) par la résistance à l'insuline et le stress oxydatif. Une association multifactorielle avec le diabète de type 1 (DT1) a été récemment mise en évidence. Le dépistage de la NAFLD vise l'identification des formes plus sévères (NASH avec fibrose) et une orientation correcte vers les hépatologues. Il s'adresse à des sous-groupes à risque, dont les patients avec un DT2. La pierre angulaire du traitement de la NAFLD est la perte pondérale, les mesures hygiéno-diététiques, la pharmacologie de l'obésité ou la chirurgie bariatrique. Pour les patients avec NAFLD et DT2, il faut considérer en priorité les analogues du GLP-1 et les agonistes PPAR, capables de faire régresser la NASH, et les iSGLT2, efficaces sur la simple stéatose.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Fatores de Risco , Casamento , Fígado , Hipoglicemiantes/uso terapêutico
13.
Endocrine ; 81(2): 340-348, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37222882

RESUMO

PURPOSE: Transsphenoidal surgery for non-functioning pituitary adenomas (NFPAs) can alter pituitary function. We assessed the rates of improvement and deterioration of pituitary function by axis and searched for predictive factors of these outcomes. METHODS: We reviewed consecutive medical files from patients having had transsphenoidal surgery for NFPA between 2004 and 2018. Pituitary functions and MRI imaging were analyzed prior and after surgery. The occurrence of recovery and new deficit were documented per axis. Prognostic factors of hormonal recovery and new deficits were searched. RESULTS: Among 137 patients analyzed, median tumor size of the NFPA was 24.8 mm and 58.4% of patients presented visual impairment. Before surgery, 91 patients (67%) had at least one abnormal pituitary axis (hypogonadism: 62.4%; hypothyroidism: 41%, adrenal insufficiency: 30.8%, growth hormone deficiency: 29.9%; increased prolactin: 50.8%). Following surgery, the recovery rate of pituitary deficiency of one axis or more was 46% and the rate of new pituitary deficiency was 10%. Rates of LH-FSH, TSH, ACTH and GH deficiency recovery were 35.7%, 30.4%, 15.4%, and 45.5% respectively. Rates of new LH-FSH, TSH, ACTH and GH deficiencies were 8.3%, 1.6%, 9.2% and 5.1% respectively. Altogether, 24.6% of patients had a global pituitary function improvement and only 7% had pituitary function worsening after surgery. Male patients and patients with hyperprolactinemia upon diagnosis were more likely to experience pituitary function recovery. No prognostic factors for the risk of new deficiencies were identified. CONCLUSION: In a real-life cohort of patients with NFPAs, recovery of hypopituitarism after surgery is more frequent than the occurrence of new deficiencies. Hence, hypopituitarism could be considered a relative indication for surgery in patients with NFPAs.


Assuntos
Hipopituitarismo , Neoplasias Hipofisárias , Humanos , Masculino , Hipófise/diagnóstico por imagem , Hipófise/cirurgia , Hipófise/patologia , Hipopituitarismo/epidemiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Hormônio Foliculoestimulante , Tireotropina , Hormônio Adrenocorticotrópico
15.
Rev Med Suisse ; 19(N° 809-10): 25-27, 2023 Jan 18.
Artigo em Francês | MEDLINE | ID: mdl-36660832

RESUMO

Diabetology is a constantly evolving discipline, many molecules appear on the market and treatment recommendations change quite frequently according to the latest published studies. It is therefore often difficult for the primary care physician to be up to date. After lifestyle measures that must of course be preferred before any drug approach, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects. The purpose of this article is to help the primary care physician to choose the most suitable pharmacological treatment for each patient, in the light of the 2022 novelties in the field of diabetes.


La diabétologie est une discipline en constante évolution. De nombreuses molécules apparaissent sur le marché et les recommandations de traitement changent assez fréquemment en fonction des dernières études publiées. Il est donc souvent difficile pour le médecin de premier recours d'être à jour. Après les mesures sur le style de vie, qu'il faut bien sûr privilégier avant toute approche médicamenteuse, la metformine reste la base pharmacologique du traitement. Les recommandations actuelles préconisent d'instaurer un inhibiteur du SGLT2 (sodium-glucose transporteur de type 2) ou un agoniste du récepteur du GLP-1 (Glucagon-like Peptide-1) après la metformine car ces molécules ont montré des effets bénéfiques cardiovasculaires et rénaux. Le but de cet article est d'aider le médecin de premier recours à choisir le traitement pharmacologique le plus adapté à chaque patient, à la lumière des nouveautés 2022 dans le domaine du diabète.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hipoglicemiantes/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1
16.
Front Endocrinol (Lausanne) ; 13: 1031633, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531463

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in the general population with a global prevalence of 25%. It is often associated with metabolic syndrome and type 2 diabetes, as insulin resistance and hyperinsulinemia are known to be favoring factors. Recent studies have described growing incidence of NAFLD in type 1 diabetes (T1D) as well. Although increasing prevalence of metabolic syndrome in these patients seems to explain part of this increase in NAFLD, other underlying mechanisms may participate in the emergence of NAFLD. Notably, some genetic factors are more associated with fatty liver disease, but their prevalence in T1D has not been evaluated. Moreover, oxidative stress, poor glucose control and long-lasting hyperglycemia, as well as exogenous insulin administration play an important role in intrahepatic fat homeostasis. The main differential diagnosis of NAFLD in T1D is glycogenic hepatopathy, which needs to be considered mostly in T1D patients with poor glycemic control. This article aims to review the prevalence and pathophysiology of NAFLD in T1D and open perspectives for clinicians taking care of T1D patients with potential hepatopathy.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hiperglicemia , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Síndrome Metabólica/epidemiologia , Prevalência , Fatores de Risco , Hiperglicemia/complicações , Hiperglicemia/epidemiologia
17.
Front Endocrinol (Lausanne) ; 13: 971745, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313762

RESUMO

Interleukin-18 (IL-18) is a classical member of the IL-1 superfamily of cytokines. As IL-1ß, IL-18 precursor is processed by inflammasome/caspase-1 into a mature and biologically active form. IL-18 binds to its specific receptor composed of two chains (IL-18Rα and IL-18Rß) to trigger a similar intracellular signaling pathway as IL-1, ultimately leading to activation of NF-κB and inflammatory processes. Independently of this IL-1-like signaling, IL-18 also specifically induces IFN-γ production, driving the Th1 immune response. In circulation, IL-18 binds to the IL-18 binding protein (IL-18BP) with high affinity, letting only a small fraction of free IL-18 able to trigger receptor-mediated signaling. In contrast to other IL-1 family members, IL-18 is produced constitutively by different cell types, suggesting implications in normal physiology. If the roles of IL-18 in inflammatory processes and infectious diseases are well described, recent experimental studies in mice have highlighted the action of IL-18 signaling in the control of energy homeostasis, pancreatic islet immunity and liver integrity during nutritional stress. At the same time, clinical observations implicate IL-18 in various metabolic diseases including obesity, type 1 and 2 diabetes and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). In the present review, we summarize and discuss both the physiological actions of IL-18 in metabolism and its potential roles in pathophysiological mechanisms leading to the most common human metabolic disorders, such as obesity, diabetes and NAFLD/NASH.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Interleucina-18 , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade
18.
Biomedicines ; 10(9)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36140303

RESUMO

We performed a systematic review and meta-analysis to assess the association between epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) and was based on a registered protocol (CRD 4201809 5493). We searched Medline and Embase until December 2021 for studies reporting on the association between EFT and NAFLD. Qualitative reviews, meta-analyses and meta-regressions were performed to explore this association. Effect sizes are reported as standardized mean differences. We included 12 studies, comprising 3610 individuals. EFT was evaluated with trans-thoracic echocardiography in nine studies, two studies using cardiac computed tomography and one study using magnetic resonance imaging (MRI). The presence of NAFLD was evaluated using transabdominal liver ultrasound in nine studies. Other studies used histology, magnetic resonance spectroscopy and MRI-derived proton density fat fraction. Liver biopsy was performed to assess the severity of NAFLD in four studies. The random-effects meta-analysis indicated that, as compared to control patients with lean livers, patients with NAFLD displayed significantly higher EFT (standardized mean difference 0.61, 95% confidence interval: 0.47−0.75, p < 0.0001, I2 = 72%). EFT was further significantly higher in patients with severe liver steatosis versus patients with mild−moderate liver steatosis (standardized mean difference 1.21 95% confidence interval: 0.26−2.16, p < 0.001, I2 S = 96%). Through the meta-regression analysis, we found that patients with increasingly higher blood levels of aspartate aminotransferase displayed an increasingly higher depth of association. The current meta-analysis suggests that EFT may represent a useful surrogate for assessing the presence and severity of NAFLD in a non-invasive manner.

19.
EClinicalMedicine ; 53: 101649, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36128334

RESUMO

Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

20.
Rev Med Suisse ; 18(797): 1802-1805, 2022 Sep 28.
Artigo em Francês | MEDLINE | ID: mdl-36170133

RESUMO

The latest ESC recommendations propose several interesting new concepts for the practitioner. The recommendations distinguish between the «apparently healthy¼ patient and the patient at specific cardiovascular risk (diabetes, renal failure, and familial hypercholesterolemia). New risk calculation tools are proposed (SCORE2 and SCORE2-OP). The proposed LDL-C targets are specific to each group, as a general rule, < 1.8 mmol/l for individuals at high risk and < 1.4 mmol/l for individuals at very high risk. Presence of risk modifiers, comorbidities and patient preferences modulates therapeutic approach which is usually based on optimizing lifestyle and statin medication when necessary.


Les dernières recommandations de l'European Society of Cardiology (ESC) introduisent plusieurs nouveaux concepts intéressants pour le praticien. Le patient «en bonne santé apparente¼ est différencié de celui à risque spécifique (diabète, insuffisance rénale et hypercholestérolémie familiale). De nouveaux outils de calcul du risque cardiovasculaire sont proposés (SCORE2 et SCORE2-OP). Les cibles de LDL-C proposées sont spécifiques à chaque groupe avec, en règle générale, une valeur < 1,8 mmol/l pour les patients à haut risque et < 1,4 mmol/l pour ceux à très haut risque. La présence de modificateurs de risque, les comorbidités et les préférences du patient modulent l'approche thérapeutique, qui repose habituellement sur le respect des règles hygiénodiététiques et, au besoin, l'administration d'une statine.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estilo de Vida , Fatores de Risco
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