RESUMO
Unveiling the key pathways underlying postnatal beta-cell proliferation can be instrumental to decipher the mechanisms of beta-cell mass plasticity to increased physiological demand of insulin during weight gain and pregnancy. Using transcriptome and global Serine Threonine Kinase activity (STK) analyses of islets from newborn (10 days old) and adult rats, we found that highly proliferative neonatal rat islet cells display a substantially elevated activity of the mitogen activated protein 3 kinase 12, also called dual leucine zipper-bearing kinase (Dlk). As a key upstream component of the c-Jun amino terminal kinase (Jnk) pathway, Dlk overexpression was associated with increased Jnk3 activity and was mainly localized in the beta-cell cytoplasm. We provide the evidence that Dlk associates with and activates Jnk3, and that this cascade stimulates the expression of Ccnd1 and Ccnd2, two essential cyclins controlling postnatal beta-cell replication. Silencing of Dlk or of Jnk3 in neonatal islet cells dramatically hampered primary beta-cell replication and the expression of the two cyclins. Moreover, the expression of Dlk, Jnk3, Ccnd1 and Ccnd2 was induced in high replicative islet beta cells from ob/ob mice during weight gain, and from pregnant female rats. In human islets from non-diabetic obese individuals, DLK expression was also cytoplasmic and the rise of the mRNA level was associated with an increase of JNK3, CCND1 and CCND2 mRNA levels, when compared to islets from lean and obese patients with diabetes. In conclusion, we find that activation of Jnk3 signalling by Dlk could be a key mechanism for adapting islet beta-cell mass during postnatal development and weight gain.
Assuntos
Células Secretoras de Insulina/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Proteína Quinase 10 Ativada por Mitógeno/metabolismo , Transdução de Sinais , Animais , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclina D2/genética , Ciclina D2/metabolismo , Feminino , Glucose/farmacologia , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/citologia , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 10 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 10 Ativada por Mitógeno/genética , Obesidade/metabolismo , Obesidade/patologia , Pâncreas/crescimento & desenvolvimento , Pâncreas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: Although HEN and HPN are important parts of home healthcare, lack of information about the number of patients concerned is surprising. This educational paper presents a review of literature concerning published national data on epidemiology of both HEN and HPN, for different countries. It compares these publications with an exhaustive retrospective observational study on our national adult population for the year 2019. METHODS: Our presented retrospective observational national study was carried out on patients aged 20 and over, divided by sex and into three age groups: 20-39, 40-59, 60 years old and over. Open data from the National Health Insurance obtained the number of patients who started a HEN or HPN during 2019 (incidence), as well as those followed in HEN or HPN during this year (prevalence). Results are compared with a literature review compiling all available publications presenting national data on epidemiology of both HEN and HPN for a same country. RESULTS: This work covered an entire national population of 50.881 948 adults. The incidence and prevalence of HEN were respectively 37.4/100 000 inhab/year and 74.0/100 000 inhab, with significant gender and age differences. The incidence and overall prevalence of HPN were respectively 22.0/100 000 inhab/year and 25.3/100 000 inhab. The prevalence of HPN during over 12 weeks was 6.2/100 000 inhab. The HEN/HPN ratio was 3:1. A total of 37 657 and 12 859 adults respectively required HEN and HPN among 50 881 948 people aged 20 and over. Published papers to compare, aggregating national data for both HEN and HPN, are only few. They do not have exhaustive data, they are often carried out on limited populations and often indiscriminately affect adults and children. CONCLUSIONS: Epidemiology of HEN and HPN remains poorly described in the literature. We present here the first results to accurately assess the incidence and prevalence of HAN on a complete national adult population and for a same year. The completeness of our data may explain these results of incidence and prevalence significantly higher than almost all available information in the existing literature, but as close as possible to real data.
Assuntos
Serviços de Assistência Domiciliar , Nutrição Parenteral no Domicílio , Adulto , Criança , Humanos , Adulto Jovem , Nutrição Enteral/métodos , Estudos Retrospectivos , Prevalência , Estudos Observacionais como AssuntoRESUMO
CONTEXT: Despite optimization of metabolic balance during pregnancy in type 1 diabetes (T1D), maternal-fetal complications remain higher than in the background population. OBJECTIVE: We examined whether there is an association between glycated hemoglobin (HbA1c) levels and these complications. METHODS: Retrospective study of pregnancies in 678 T1D subjects at Lille Hospital (1997-2019). The association between variations in HbA1c levels and complications was examined. The composite criterion (CC) was defined as having at least 1 of the following complications: prematurity, pre-eclampsia, large for gestational age (LGA), small for gestational age (SGA), or cesarean section. RESULTS: Among the 678 births, median preconception HbA1c was 7.2% (55 mmol/mol), 361 were LGA (56%), 29 were SGA (4.5%), and 504 were births without preterm delivery (76.1%). The CC occurred in 81.8%. Higher HbA1c during the first trimester was associated with the CC (OR 1.04; 95% CI 1.02-1.06 per 0.1% increase; Pâ <â .001). Higher HbA1c during the third trimester was associated with the CC (OR 1.07; 95% CI 1.03-1.10 per 0.1% increase; Pâ <â .001). The group defined by a first trimester Hba1c >6.5% (48 mmol/mol) and a third trimester HbA1c <6% was associated with an increased rate of the CC (OR 2.81; 95% CI 1.01-7.86) and an increased rate of LGA (OR 2.20; 95% CI 1.01- 4.78). CONCLUSION: Elevated HbA1c is associated with maternal-fetal complications. Despite optimization of metabolic balance during the third trimester, for patients with early glycemic imbalance the risk of LGA persists.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Macrossomia Fetal/epidemiologia , Hemoglobinas Glicadas/análise , Pré-Eclâmpsia/epidemiologia , Gravidez em Diabéticas/sangue , Adulto , Cesárea/estatística & dados numéricos , Diabetes Mellitus Tipo 1/sangue , Feminino , Macrossomia Fetal/etiologia , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia/etiologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricosRESUMO
Lipomas are the most common soft tissue tumors and are malignant in only 1% of cases. Lipomatosis is defined as the presence of multiple benign lipomas on the body, without lipoatrophy. Their impact on quality of life is significant. Different entities have been described such as symmetrical multiple lipomatosis (MSL), also called Madelung's disease and familial multiple lipomatosis (FML). MSL occurs preferentially in men (but also women) who are alcohol abuser. There are different subtypes of the disease, the most classic of which affects the upper body and the nuchal region with a buffalo hump appearance. A metabolic component with obesity is frequent. In contrast to Dercum's disease, there is no pain. SAOS, complications of the metabolic syndrome and of alcohol abuse including cancers, may be associated and should be screened. FML has been little described in the literature since Brodie's first report in 1846. FML occurs preferentially in the third decade but equally in women and men. Its autosomal dominant component is classically accepted with variable penetrance within the same family. Association with naevi, angiomas, polyneuropathies and with gastrointestinal comorbidities has been reported. Interestingly, and in contrast with most lipodystrophy disorders, the patients show an insulin sensitivity profile. A better understanding of the underlying pathophysiological mechanisms would open up avenues on therapeutic research, since treatments are only symptomatic to date.
Assuntos
Lipomatose Múltipla Familiar , Lipomatose Simétrica Múltipla , Alcoolismo/complicações , Lipomatose Múltipla Familiar/diagnóstico , Lipomatose Múltipla Familiar/genética , Lipomatose Múltipla Familiar/patologia , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Resistência à Insulina , Lipomatose Simétrica Múltipla/diagnóstico , Lipomatose Simétrica Múltipla/genética , Lipomatose Simétrica Múltipla/patologia , Masculino , Síndrome Metabólica/complicações , Proteínas Mitocondriais/genética , Obesidade/complicações , Fenótipo , Qualidade de VidaRESUMO
BACKGROUND & AIMS: The use of long-term taurolidine locks (LTTL) seems to be effective in preventing catheter-related blood stream infections (CRBSI), especially in patients on home parenteral nutrition (HPN). This work targets the cost-effectiveness of LTTL in a cohort of adult HPN patients. METHODS: A monocentric mirror-image design study was conducted in our referral centre among long-term HPN patients experiencing recurrent CRBSI. From 7th January 2011, LTTL were started after the third CRBSI episode within 12 months. CRBSI data was prospectively collected until 7th January 2013, in the same way as it had retrospectively been done before initiating LTTL. A cost-effective analysis was conducted to estimate the incremental costs and effects on CRBSI with LTTL. The efficacy of LTTL on CRBSI rate was assessed over 1000 days of catheter use. RESULTS: A total of 31,100 catheter days were analysed in 37 patients (median [interquartile range (IQR)]) aged 58 [42-68] years. The mean ± SD proven CRBSI rate was 3.18 ± 3.51 per 1000 catheter days before the introduction of LTTL and 0.39 ± 1.50 per 1000 catheter days after its introduction (p < 0.0001). Considering both proven and probable CRBSI requiring hospital management, LTTL reduced by (mean [bootstrap CI 95%]) -2.63 [-3.26 to -2.06] infections per patient (from 2.89 [2.31 to 3.49] before to 0.26 [0.13 to 0.41] after) as well as incremental costs by -7 258 [-10 450 to -4 016] (from 11 176 [8 004 to 14 968] before to 3 918 [2 390 to 5 445] after). CONCLUSION: Implementing LTTL to prevent recurrent CRBSI is cost-effective by dramatically decreasing their incidence.
Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Quimioprevenção/economia , Taurina/análogos & derivados , Tiadiazinas/economia , Adulto , Infecções Relacionadas a Cateter/epidemiologia , Quimioprevenção/métodos , Análise Custo-Benefício , Feminino , Hospitalização/economia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral no Domicílio , Estudos Prospectivos , Recidiva , Projetos de Pesquisa , Estudos Retrospectivos , Taurina/administração & dosagem , Taurina/economia , Tiadiazinas/administração & dosagem , Resultado do TratamentoRESUMO
In contrast to obesity, which is very frequent, lipomatosis and lipodystrophy syndromes are rare diseases of adipose tissue. Lipodystrophy syndromes are characterized by metabolic abnormalities associated with partial or generalized lipoatrophy. Lipomatosis is defined by the presence of several body lipomas without lipoatrophy. Dercum's disease (DD) and Roch-Leri mesosomatous lipomatosis (RLML) are rare and poorly characterized forms of lipomatosis. They have raised little clinical interest despite the non-negligible consequences of DD on quality of life. The main clinical presentation of these diseases includes multiple lipomas, which are painful in DD (in contrast to RLML). The two diseases are frequently associated with obesity and metabolic syndrome, with hypertension, diabetes, or dyslipidemia. The long-term course of the diseases remains poorly described. DD affects mainly women, whereas RLML mostly affects men. In both diseases lipomas are found on the back and thighs, as well as on the abdomen in DD and the forearms in RLML. The painful lipomas tend to recur after surgery in DD (in contrast to RLML). Most cases are sporadic. No specific treatment has been identified, as the pathophysiology remains unknown. Nevertheless, low-grade fat inflammation and specific abnormalities such as hyperbasophilia deserve further investigation. The aim of this review is to analyze the available literature on the topic.
RESUMO
OBJECTIVE: Pregnancy has been associated with development and progression of diabetic retinopathy (DR), but incidence of DR remains unclear. We assessed DR progression rate and its predictors during pregnancies in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We report the retrospective data from pregnancies in patients with type 1 diabetes followed in Lille, France (1997-2015). Eye examination was performed every 3 months or every month in case of severe nonproliferative retinopathy or progression. Progression was defined by DR degradation (≥1 stage of the Early Treatment Diabetic Retinopathy Study [ETDRS] classification); it included DR development and worsening in patients without and with prepregnancy DR, respectively. RESULTS: A total of 499 pregnancies in 375 patients were included; prepregnancy retinopathy was present in 30.3%. Progression, development, and worsening rates were 21.8%, 24.4% of those without retinopathy, and 15.9% of those with retinopathy, respectively. Development of sight-threatening retinopathy was rare. Progression mainly occurred in early or midpregnancy. Elevated prepregnancy HbA1c and duration of diabetes ≥10 years were predictors of DR progression. Among pregnancies with prepregnancy DR, continuous subcutaneous insulin infusion (CSII) tended to decrease the risk of DR progression. Among CSII-treated patients, those with prepregnancy DR had a significantly decreased risk of DR progression. Among the 270 pregnancies of women with any DR during pregnancy who returned for a postpartum ophthalmologic examination, the rate of progression was only 4.1% and the rate of regression was 9.3%. CONCLUSIONS: This study provides epidemiologic data on progression of retinopathy during pregnancy and will be useful for future guidelines for retinopathy screening.