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1.
Drug Resist Updat ; 73: 101054, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38277756

RESUMO

AIMS: Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance. METHODS: Cancer Genome Atlas-liver HCC data and unbiased gene set enrichment analyses were used to identify SIRT7 as a potential effector molecule in sorafenib acquired resistance. Two types of SIRT7 chemical inhibitors were developed to evaluate its therapeutic properties when synergized with sorafenib. Mass spectrometry was performed to discover a direct target of SIRT7, DDX3X, and DDX3X deacetylation levels and protein stability were explored. Moreover, an in vivo xenograft model was used to confirm anti-tumor effect of SIRT7 and DDX3X chemical inhibitors combined with sorafenib. RESULTS: SIRT7 inhibition mediated DDX3X depletion can re-sensitize acquired sorafenib resistance by disrupting NLRP3 inflammasome assembly, finally suppressing hyperactive ERK1/2 signaling in response to NLRP3 inflammasome-mediated IL-1ß inhibition. CONCLUSIONS: SIRT7 is responsible for sorafenib acquired resistance, and its inhibition would be beneficial when combined with sorafenib by suppressing hyperactive pro-cell survival ERK1/2 signaling.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sirtuínas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Fosforilação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sistema de Sinalização das MAP Quinases , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Proliferação de Células , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/farmacologia , Sirtuínas/genética , Sirtuínas/metabolismo , Sirtuínas/farmacologia
2.
Nature ; 563(7731): 354-359, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30356218

RESUMO

Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for several enzymes, including the sirtuin family of NAD+-dependent protein deacylases. Beneficial effects of increased NAD+ levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-ß-carboxymuconate-ε-semialdehyde in the de novo NAD+ synthesis pathway, controls cellular NAD+ levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD+ synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD+ levels, sirtuin activity and mitochondrial homeostasis in kidney and liver.


Assuntos
Carboxiliases/metabolismo , Sequência Conservada , Evolução Molecular , Saúde , Mitocôndrias/fisiologia , NAD/biossíntese , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/metabolismo , Carboxiliases/antagonistas & inibidores , Carboxiliases/química , Carboxiliases/deficiência , Linhagem Celular , Colina , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Rim/citologia , Rim/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Masculino , Metionina/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ratos , Sirtuínas/metabolismo
3.
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
4.
Rev Med Suisse ; 20(876): 1069-1073, 2024 May 29.
Artigo em Francês | MEDLINE | ID: mdl-38812338

RESUMO

C-peptide measurement allows an estimation of the residual endogenous insulin secretion in diabetic patients. Nowadays plasmatic testing is convenient and unexpensive, but we lack standardized tests. Therefore, there are no official recommendation regarding its use. As an indication, in some circumstances, C-peptide measurement could be used to specify the type of diabetes, help guide the treatment strategy and potentially assess the risk for complications. Its use is still limited and not recommended on a routine base for all patients living with diabetes, but in the future, tests standardization and establishment of reference ranges could give more insight on the clinical relevance of C-peptide measurement.


Le dosage du peptide-C est une mesure permettant d'évaluer la sécrétion endogène résiduelle d'insuline chez les patients diabétiques. Le dosage plasmatique est facilement réalisable actuellement, pour un coût modeste, mais l'absence de standardisation des tests ne permet pas d'émettre des recommandations officielles par rapport à son utilisation. À titre indicatif, dans certaines situations, le dosage du peptide-C peut être utilisé pour préciser le type de diabète, guider les traitements médicamenteux et potentiellement évaluer les risques de complications. Son utilisation est pour le moment limitée et n'est pas recommandée en routine pour tous les patients atteints de diabète, mais à l'avenir, la formalisation du dosage et l'établissement de valeurs de référence pourraient permettre de définir son utilisation clinique.


Assuntos
Peptídeo C , Secreção de Insulina , Insulina , Humanos , Peptídeo C/sangue , Peptídeo C/metabolismo , Insulina/metabolismo , Secreção de Insulina/fisiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/metabolismo , Diabetes Mellitus/diagnóstico
5.
Rev Med Suisse ; 20(861): 338-341, 2024 Feb 14.
Artigo em Francês | MEDLINE | ID: mdl-38353433

RESUMO

Diabetes is a chronic and progressive disease that affects an increasing number of patients. The prevalence of associated psychological comorbidities is high and often requires the implementation of targeted psychological interventions. Pancreas or islet transplantation remains a therapeutic option to consider, for a part of patients with type 1 diabetes unstable disease or established complications. From the clinical indication to the waiting period for a transplantation, then to the postoperative and long-term care, the diabetic patient is found to experience perpetual changes that may test his adaptability. In this article, the psychological aspects of the pancreas or islet transplantation, as well as the role of a liaison psychiatrist in a transplantation unit will be discussed.


Le diabète est une maladie chronique et évolutive atteignant un nombre croissant de patients. La prévalence des comorbidités psychiques associées est élevée et nécessite souvent l'implémentation d'interventions psychologiques ciblées. La transplantation du pancréas ou d'îlots de Langerhans est une option thérapeutique à considérer pour certains patients avec un diabète de type 1 instable ou des complications installées. De l'indication clinique à la période d'attente pour une greffe, puis des suites postopératoires jusqu'à la vie d'après la greffe, le patient diabétique vit des transitions multiples le mettant à l'épreuve. Dans cet article, nous discutons les aspects psychologiques de ces transplantations ainsi que les interventions du psychiatre de liaison au sein d'un service de transplantation.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Transplante de Pâncreas , Humanos , Diabetes Mellitus Tipo 1/cirurgia , Comorbidade , Pâncreas
6.
J Cell Mol Med ; 27(9): 1157-1167, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36992609

RESUMO

Growth and differentiation factor 15 (GDF15) is a member of the transforming growth factor-ß (TGF-ß) superfamily. GDF15 has been linked with several metabolic syndrome pathologies such as obesity and cardiovascular diseases. GDF15 is considered to be a metabolic regulator, although its precise mechanisms of action remain to be determined. Glial cell-derived neurotrophic factor family receptor alpha-like (GRAL), located in the hindbrain, has been identified as the receptor for GDF15 and signals through the coreceptor receptor tyrosine kinase (RET). Administration of GDF15 analogues in preclinical studies using various animal models has consistently been shown to induce weight loss through a reduction in food intake. GDF15, therefore, represents an attractive target to combat the current global obesity epidemic. In this article, we review current knowledge on GDF15 and its involvement in metabolic syndrome.


Assuntos
Síndrome Metabólica , Animais , Fator 15 de Diferenciação de Crescimento/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Obesidade/metabolismo , Redução de Peso
7.
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
8.
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
9.
Rev Med Suisse ; 19(829): 1072-1077, 2023 May 31.
Artigo em Francês | MEDLINE | ID: mdl-37260202

RESUMO

The management of a patient with type 2 diabetes is well known and is the subject of numerous studies. Protein-calorie malnutrition, on the other hand, is an entity that is still under-diagnosed and under-treated. When artificial nutrition is introduced, glucose homeostasis can be disturbed in case of (pre-)diabetes. To date, few recommendations based on expert opinion exist on the management of diabetes after the introduction of enteral or parenteral nutrition. This article proposes an algorithm for the management of type 2 diabetes when oral nutritional supplements are introduced.


La prise en charge d'un patient diabétique de type 2 est bien connue et fait l'objet de nombreuses études. La dénutrition protéino-calorique quant à elle est une entité encore sous-diagnostiquée et sous-traitée. Lors de la mise en place d'une nutrition artificielle, l'équilibre glycémique peut être perturbé en cas de prédiabète ou de diabète. À ce jour, quelques recommandations basées sur des avis d'experts existent sur la prise en charge du diabète après la mise en place d'une nutrition entérale ou parentérale. Cet article propose un algorithme de prise en charge du diabète de type 2, lors de l'introduction de suppléments nutritifs oraux.


Assuntos
Diabetes Mellitus Tipo 2 , Desnutrição , Humanos , Nutrição Enteral , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Estado Nutricional , Nutrição Parenteral , Desnutrição/terapia
10.
Ann Surg ; 276(2): 233-238, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35623048

RESUMO

BACKGROUND: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown. OBJECTIVE: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE). SUMMARY OF BACKGROUND DATA: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. METHODS: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up". RESULTS: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. CONCLUSIONS: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way. TRIAL REGISTRATION: ClinicalTrials NCT03615807.


Assuntos
Diabetes Mellitus , Pé Diabético , Osteomielite , Infecções dos Tecidos Moles , Idoso , Antibacterianos , Desbridamento , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/complicações , Pé Diabético/tratamento farmacológico , Feminino , Humanos , Masculino , Osteomielite/induzido quimicamente , Osteomielite/etiologia , Projetos Piloto , Infecções dos Tecidos Moles/tratamento farmacológico
11.
Rev Med Suisse ; 18(764-5): 21-24, 2022 Jan 19.
Artigo em Francês | MEDLINE | ID: mdl-35048574

RESUMO

Diabetes is a rapidly evolving discipline ; numerous new molecules are available and recommendations regarding treatment change. However, these rapid changes are sometimes difficult to follow for general practitioners. Metformin remains the cornerstone of type 2 diabetes treatment after lifestyle modifications, which should always be encouraged before medications. Currently, the best classes to add after metformin are SGLT2 inhibitors and GLP-1 receptor agonists, as these molecules showed some cardiovascular and renal beneficial effects in dedicated studies. The aim of this article is to guide the general practitioner in choosing the most suitable pharmacological treatment for each patient, in light of the novelties in the field of diabetes that appeared during the year 2021.


La diabétologie est une discipline qui évolue rapidement, de nombreuses molécules apparaissent sur le marché et les recommandations de traitement changent. 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 bien sûr privilégier avant toute approche médicamenteuse, la metformine reste le pilier 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 dans des études. Le but de ce bref article est d'aider le médecin de premier recours à choisir le traitement pharmacologique le plus adapté à chaque patient·e, à la lumière des nouveautés 2021 dans le domaine du diabète.


Assuntos
Diabetes Mellitus Tipo 2 , Clínicos Gerais , Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
12.
Rev Med Suisse ; 18(784): 1100-1105, 2022 Jun 01.
Artigo em Francês | MEDLINE | ID: mdl-35647747

RESUMO

Insulin allergy is a rare entity, complex to manage. Several types of hypersensitivity reaction are described, depending on the allergens (insulin itself vs additives). Type I, so-called immediate, IgE-mediated reactions are the most common. Their management requires a careful history and examination, as well as an allergological consult. If an IgE-mediated allergy is confirmed, insulin avoidance is recommended whenever possible. If insulin treatment is mandatory, another type of insulin may be offered. In case of failure, desensitization should be discussed, either via a dedicated protocol, or via insulin pump. In this article, we summarize the available data from the literature.


L'allergie à l'insuline est une entité rare, complexe à prendre en charge. Plusieurs types de réactions d'hypersensibilité sont décrits, selon les agents allergènes (insuline même vs additifs). Les réactions de type I, dites immédiates, IgE (immunoglobulines E) médiées sont les plus fréquentes. Leur prise en charge nécessite une anamnèse et un examen minutieux, ainsi qu'un avis allergologique. En cas de confirmation d'allergie IgE médiée, une éviction des insulines est dans la mesure du possible recommandée. Si la poursuite des traitements insuliniques est inévitable, un autre type d'insuline peut être proposé. En cas d'échec, une induction de tolérance devrait être discutée, soit via un protocole dédié, soit via la mise sous pompe à insuline. Nous résumons dans cet article les données de la littérature à disposition.


Assuntos
Hipersensibilidade a Drogas , Alérgenos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Humanos , Imunoglobulina E , Insulina/efeitos adversos
13.
Clin Infect Dis ; 73(7): e1539-e1545, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33242083

RESUMO

BACKGROUND: In patients with diabetic foot osteomyelitis (DFO) who underwent surgical debridement, we investigated whether a short (3 weeks) duration compared with a long (6 weeks) duration of systemic antibiotic treatment is associated with noninferior results for clinical remission and adverse events (AEs). METHODS: In this prospective, randomized, noninferiority pilot trial, we randomized (allocation 1:1) patients with DFO after surgical debridement to either a 3-week or a 6-week course of antibiotic therapy. The minimal duration of follow-up after the end of therapy was 2 months. We compared outcomes using Cox regression and noninferiority analyses (25% margin, power 80%). RESULTS: Among 93 enrolled patients (18% females; median age 65 years), 44 were randomized to the 3-week arm and 49 to the 6-week arm. The median number of surgical debridements was 1 (range, 0-2 interventions). In the intention-to-treat (ITT) population, remission occurred in 37 (84%) of the patients in the 3-week arm compared with 36 (73%) in the 6-week arm (P = .21). The number of AEs was similar in the 2 study arms (17/44 vs 16/49; P = .51), as were the remission incidences in the per-protocol (PP) population (33/39 vs 32/43; P = .26). In multivariate analysis, treatment with the shorter antibiotic course was not significantly associated with remission (ITT population: hazard ratio [HR], 1.1 [95% confidence interval {CI}, .6-1.7]; PP population: HR, 0.8 [95% CI: .5-1.4]). CONCLUSIONS: In this randomized controlled pilot trial, a postdebridement systemic antibiotic therapy course for DFO of 3 weeks gave similar (and statistically noninferior) incidences of remission and AE to a course of 6 weeks. CLINICAL TRIALS REGISTRATION: NCT03615807; BASEC 2016-01008 (Switzerland).


Assuntos
Diabetes Mellitus , Pé Diabético , Osteomielite , Idoso , Antibacterianos/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Pé Diabético/cirurgia , Feminino , Humanos , Masculino , Osteomielite/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos
14.
Diabetes Obes Metab ; 23(2): 637-641, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33026129

RESUMO

Clinicians frequently monitor serum C-reactive protein (CRP) levels during therapy for diabetic foot infections (DFIs), but evidence supporting this is unclear. Using a database from prospective controlled DFI trials, with fixed duration of antibiotic therapy, we correlated the CRP levels at study enrolment and at end of therapy (EOT). Among 159 DFI episodes, 93 involved the bone and 66 the soft tissues. Overall, treatment cured 122 infections (77%), while 37 episodes (23%) recurred after a median of 53 days. The median CRP in the groups with cure versus failure differed minimally at enrolment (median 67 vs. 81 mg/L) or EOT (7 vs. 10 mg/L). Similarly, there was negligible difference in the percentage of CRP levels that normalized at EOT (39% vs. 35%). In our prospective cohorts, a blunt iterative monitoring of CRP during DFI treatment, without correlation with clinical findings, failed to predict treatment failures.


Assuntos
Diabetes Mellitus , Pé Diabético , Antibacterianos/uso terapêutico , Proteína C-Reativa/análise , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Humanos , Estudos Prospectivos , Recidiva
15.
Rev Med Suisse ; 17(723): 188-191, 2021 Jan 27.
Artigo em Francês | MEDLINE | ID: mdl-33507658

RESUMO

Diabetes is a rapidly evolving discipline, numerous new molecules and recommendations are available. However, these rapid changes are sometimes difficult to follow for general practitioners. Metformin remains the cornerstone of type 2 diabetes treatment after lifestyle modifications, which should always be encouraged before medications. Currently, the best classes to add after metformin seem to be SGLT2 inhibitors and GLP-1 receptor agonists, as these molecules showed some cardiovascular and renal beneficial effects in dedicated studies. Nevertheless, the current pharmacological plethora is paradoxically associated with clinical inertia as general practitioners may be in trouble finding the right medication. This article will highlight novelties in the field of diabetes during the year 2020.


La diabétologie est une discipline qui évolue rapidement, de nombreuses molécules apparaissent sur le marché, de même que de nouvelles recommandations, qu'il est souvent difficile de suivre pour le médecin de premier recours. Les dernières recommandations, après les mesures du style de vie qu'il faut bien sûr privilégier avant toute approche médicamenteuse, sont d'initier un inhibiteur du cotransporteur sodium-glucose de type 2 ou un agoniste du récepteur du Glucagon-Like Peptide-1 après la metformine, cette dernière restant le pilier pharmacologique du traitement du diabète de type 2. Au vu de la jungle thérapeutique actuelle dans le traitement du diabète de type 2, le but de ce bref article est d'aider le médecin de premier recours à s'y retrouver en faisant le point sur les nouveautés 2020 dans le domaine du diabète.


Assuntos
Diabetes Mellitus Tipo 2 , Clínicos Gerais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipoglicemiantes/uso terapêutico , Metformina , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
16.
Rev Med Suisse ; 17(741): 1062-1066, 2021 Jun 02.
Artigo em Francês | MEDLINE | ID: mdl-34077036

RESUMO

MODY diabetes, for Maturity Onset Diabetes of the Young, is a form of monogenic diabetes characterized by a typical onset before the age of 25 years, the lack of autoimmunity against the b cells of the pancreas, a preserved ß cells function and an autosomal dominant mode of inheritance. This type of diabetes constitutes 2 to 5% of all cases of diabetes but remains often undiagnosed. Nearly 15 MODY subtypes have been identified to date. The 3 most common subtypes are caused by mutations in the genes encoding glucokinase, HNF1a and HNF4a, and account for approximately 80% of all MODY cases. Carrying out a genetic test can thus make it possible to make the diagnosis of MODY diabetes and to set up an appropriate treatment. In this article we will discuss these 3 main MODY sub-type, although there are other forms, which may be characterized by associated specific organ damage.


Le diabète Maturity Onset Diabetes of the Young (MODY) est une forme de diabète monogénique se caractérisant par une apparition typique avant l'âge de 25 ans, l'absence d'autoimmunité contre les cellules ß du pancréas, une fonction préservée des cellules ß et un mode de transmission autosomique dominant. Ce type de diabète constitue 2 à 5 % de tous les cas de diabètes, mais reste souvent non diagnostiqué. Près de 15 sous-types sont, à ce jour, identifiés. Les 3 les plus fréquents sont causés par des mutations des gènes codant pour la glucokinase, HNF1α et HNF4α, qui représentent environ 80 % des cas de MODY. La réalisation d'un test génétique peut ainsi permettre de poser le diagnostic de MODY et mettre en place un traitement approprié. Dans cet article nous discutons de ces 3 sous-types principaux de MODY, bien qu'il existe d'autres formes plus rares pouvant se caractériser par des atteintes d'organes spécifiques associées.


Assuntos
Diabetes Mellitus Tipo 2 , Fator 4 Nuclear de Hepatócito , Adulto , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Fator 4 Nuclear de Hepatócito/genética , Humanos , Mutação
17.
BMC Endocr Disord ; 20(1): 155, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066762

RESUMO

BACKGROUND: Detailed description of hyperglycemia management in diabetic patients infected with SARS-CoV-2 remain limited, although patients with diabetes show higher complication and mortality rate than patients without diabetes. Transient non-severe increased insulin requirement in patients hospitalized for medical conditions such as sepsis or myocardial infarction is a well-known phenomenon. However, extremely high-dose insulin requirement remains a very rarely reported entity. Here, we report the case of an extreme and transitory insulin requirement episode in a type 2 diabetic patient presenting an acute respiratory distress syndrome caused by SARS-CoV-2. CASE PRESENTATION: A 57-year-old man resident in Geneva, Switzerland, previously known for type 2 diabetes for 3 years was admitted for an aggravation of his dyspnea. His type 2 diabetes was treated only with metformin and his latest Hb1Ac was 6.1%. Chest CT SCAN showed a bilateral multilobar ground-glass opacification. Twenty-four hours after his admission he presented a worsening of dyspnea and severe hypoxemia requiring a transfer to the intensive care unit rapidly followed by oro-tracheal intubation for mechanical ventilation support. A bronchoalveolar lavage was performed and test of SARS-CoV-2 by RT-qPCR assay was positive. At day 3, he presented a rapidly progressive insulin requirement at a rate of up to 50 units/hour intravenous insulin aspart. Despite the high insulin doses, he maintained an elevated plasma glucose level at 270 mg/dL on average. His extremely high-dose insulin requirement "resolved" at day 9, and the insulin infusion rate was rapidly reduced. CONCLUSIONS: This case may reflect a specific and profound impact of SARS-CoV-2 on metabolic homeostasis, in particular in diabetic patients that appear more prone to complications of COVID-19 infection. Yet, the mechanisms behind this remain to be elucidated. The optimal management of hyperglycemia of diabetic patients infected with SARS-CoV-2 has yet not be defined, however insulin remain the mainstay of treatment approach. Report of extreme dysregulation of chronic conditions such as diabetes in patients with COVID-19 may help clinicians to better take care of patients during the pandemic of SARS-CoV-2. To the best of our knowledge this is the first description of extremely high-dose insulin requirement in patient with COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pneumonia Viral/complicações , COVID-19 , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/virologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , SARS-CoV-2
18.
Rev Med Suisse ; 16(697): 1197-1199, 2020 Jun 10.
Artigo em Francês | MEDLINE | ID: mdl-32520458

RESUMO

Nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease and is associated with type 2 diabetes in almost 60% of the cases. Its pathophysiology is complex: it consists in the accumulation of intrahepatocyte lipids and in the development of inflammation and fibrosis. Its diagnosis is based on imaging and blood tests to rule out other causes of liver damage. In doubt, the liver biopsy is the gold standard. There is currently no specific treatment available, but many molecules will soon be on the market. Therefore, it is important to actively check for NASH in type 2 diabetic patients, specially to avoid its progression to cirrhosis.


La stéatohépatite non alcoolique (Nonalcoholic Steatohepatitis, NASH) est l'affection hépatique chronique la plus fréquente; elle est associée au diabète de type 2 dans près de 60% des cas. Sa physiopathologie est complexe: elle est caractérisée par l'accumulation de lipides intrahépatocytaires et le développement d'inflammation et de fibrose. Son diagnostic repose sur les résultats de l'imagerie et des tests sanguins, afin d'exclure d'autres causes d'atteinte hépatique. En cas de doute, la biopsie hépatique représente le gold-standard. Il n'y a à l'heure actuelle pas de traitement spécifique disponible, mais de nombreuses molécules vont prochainement arriver sur le marché. Il est donc important de rechercher activement la NASH chez les patients diabétiques de type 2, afin notamment d'éviter la progression vers la cirrhose.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Biópsia , Humanos , Cirrose Hepática/etiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico
19.
Rev Med Suisse ; 16(676-7): 31-33, 2020 Jan 15.
Artigo em Francês | MEDLINE | ID: mdl-31961079

RESUMO

Diabetes is a rapidly evolving discipline, numerous new molecules and recommendations are available. This allows for a better follow up of our patients. Moreover, every new molecule devoted to treat type 2 diabetes must undergo a cardiovascular safety study. In recent years, some of these studies revealed beneficial cardiovascular and/or renal effects, which represents a benefit for our patients. Nevertheless, this pharmacological plethora is paradoxically associated with clinical inertia as general practitioners may be in trouble finding the right medication. This article will highlight novelties in the field of diabetes during the year 2019.


La diabétologie est une discipline qui évolue rapidement, de nombreuses nouvelles molécules apparaissent sur le marché, de même que de nouvelles recommandations. Ceci enrichi la panoplie des possibilités thérapeutiques pour nos patients. De plus, tout nouvel antidiabétique apparaissant sur le marché dans le diabète de type 2 doit faire l'objet d'une étude de sécurité cardiovasculaire, et ces dernières années ont vu l'apparition de molécules potentiellement favorables sur le plan cardiovasculaire et/ou rénal, ce qui est bien entendu un bénéfice pour nos patients. Cependant, cette pléthore de nouveaux traitements peut s'accompagner paradoxalement d'une certaine inertie thérapeutique et de difficultés pour les médecins de premier recours à s'y retrouver. Cet article a pour but de faire le point sur les nouveautés 2019 dans le domaine du diabète.


Assuntos
Diabetes Mellitus Tipo 2 , Clínicos Gerais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos
20.
Rev Med Suisse ; 16(683): 409-411, 2020 Feb 26.
Artigo em Francês | MEDLINE | ID: mdl-32129018

RESUMO

The onset of diabetes after kidney transplantation is a frequently encountered entity by both the nephrologist, the diabetologist and the primary care physician. This article discusses various aspects related to diabetes after kidney transplantation such as epidemiology, risk factors, pathogenesis, diagnosis, associated complications and therapeutic management.


La survenue d'un diabète après transplantation rénale est une entité fréquemment rencontrée tant par le néphrologue, le diabétologue que par le médecin de premier recours. Cet article fait le point sur différents aspects liés au diabète après transplantation rénale tels que l'épidémiologie, les facteurs de risque, la pathogenèse, le diagnostic, les complications associées et la prise en charge thérapeutique.


Assuntos
Diabetes Mellitus , Transplante de Rim , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Humanos , Fatores de Risco
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