Vitamin D Status, Insulin Resistance, Leptin-To-Adiponectin Ratio in Adolescents: Results of a 1-Year Lifestyle Intervention

AIM: We aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D], insulin resistance and leptin-to-adiponectin (L/A) ratio in Guadeloupean children and adolescents and to analyse the changes in 25(OH)D levels after a 1-year lifestyle intervention program.METHODS: 25(OH)D concentrations were measured via a chemiluminescence assay. Cardiometabolic risk factors, homoeostasis model assessment of insulin resistance (HOMA-IR), and adipokines were measured. The lifestyle intervention included dietary counselling, regular physical activity.RESULTS: Among 117 girls and boys (11–15 years old, 31.6% obese), 40% had vitamin D deficiency (25(OH)D levels < 20 ng/mL). With linear regression models where 25(OH)D and HOMA-IR acted as independent variables and age, sex, BMI, L/A ratio as covariates, 25(OH)D was significantly associated with HOMA-IR alone (P = 0.036). HOMA-IR was also associated with BMI z-score ≥ 2, L/A ratio and an interaction term BMI z-score ≥ 2*L/A ratio (P < 0.001 for all). After one year, in 78 children/adolescent, mean serum 25(OH)D increased significantly from 21.4 ± 4.9 ng/mL at baseline to 23.2 ± 6.0 after 1 year; P = 0.003 whereas BMI z-score, HOMA-IR and L/A ratio decreased significantly (P = 0.003, P < 0.001 and P = 0.012; respectively).CONCLUSION: The association between 25(OH)D and HOMA-IR, independently of obesity and the high prevalence of vitamin D deficiency should be considered in order to prevent the later incidence of T2DM. A healthy lifestyle including non-sedentary and outdoor activities could be a way for improving vitamin D status

Metabolic profile associated with vitamin D status and polymorphisms in genes encoding the receptor and its specific carrier in a Caribbean population : parameters associated with the "sex hormone binding globulin" in a Caucasian population dysmetabolic

En Guadeloupe, la prévalence du diabète est deux fois plus élevée qu'en France hexagonale, avec une prédominance féminine. En dehors des facteurs environnementaux, la vitamine D et certains polymorphismes de gènes impliqués dans son métabolisme seraient associés à un risque de pathologies métaboliques. Les androgènes sont également associés aux anomalies du métabolisme glucidique, soit directement, soit via leur transporteur SHBG (Sex Hormone Binding Protein). Nous avons émis les hypothèses de recherche suivantes: 11 le statut en vitamine D et les polymorphismes des gènes impliqués dans son métabolisme pourraient être associés aux paramètres métaboliques chez des sujets Afro-Caribéens (AC). Ils expliqueraient l'importance des pathologies cardiométaboliques en Guadeloupe. 2/ la SHBG pourrait être associée aux anomalies du métabolisme glucidique, indépendamment des stéroïdes sexuels. Nos travaux sont présentés dans 4 études. Nous avons mis en évidence une prévalence élevée du déficit en vitamine D chez les sujets AC diabétiques de type 2. Nous avons trouvé une association significative entre le statut vitaminique D et le risque cardiométabolique chez ces sujets, mais aussi dans une population de sujets en hémodialyse chronique. Les polymorphismes des gènes impliqués dans le métabolisme de la vitamine D sont aussi associés à ce risque. Chez les sujets dysmétaboliques, une relation entre la SHBG, la graisse intra-hépatique, les hépatokines et les paramètres métaboliques a été mise en évidence, indépendamment des stéroïdes sexuels. En conclusion, la vitamine D et la SHBG pourraient être des marqueurs d'intérêt pour le dépistage des sujets à haut risque cardiométabolique.In Guadeloupe, the prevalence of diabetes is two times higher than in Metropolitan France, with a female predominance. Apart from environmental factors, vitamin D and polymorphisms of genes involved in vitamin D metabolism would be associated with increased risk of metabolic diseases. Androgens are also associated with abnormal glucose metabolism, directly or through the Sex Hormone Binding Protein (SHBG). Our main hypotheses were: 11 Vitamin D status and polymorphisms of genes involved in its metabolism may be associated with metabolic pammeters in Afro-Caribbean (AC). They could explain the importance of cardiometabolic diseases in Guadeloupe. 2/ SHBG may be associated with abnormal glucose metabolism, independently of sex steroids. Our research is presente<! in four studies. We have demonstrated a high prevalence of vitamin D deficiency in AC patients with type 2 diabetes. We found a significant association between vitamin D status and cardiometabolic risk in these subjects, but also in a population of patients undergoing in chronic hemodialysis. Polymorphisms in genes involved in vitam in D metabolism are also associated with this risk, In dysmetabolic patients, a relationship between SHBG, intmhepatic fat, hépatokines and metabolic parameters was demonstrated, independently of sex steroids hormones. In conclusion, vitamin D and SHBG may be markers of interest for screening patients at high cardiometabolic risk

Prise en charge médicale de l'orbitopathie basedowienne (corticothérapie orale et intraveineuse)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hyperparathyroïdie primaire et déficit en vitamine D (étude lilloise)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les marqueurs sériques de l'apoptose Fas soluble et Bcl-2 dans les thyropathies iatrogènes et auto-immunes

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

In silico development of novels radiopharmaceuticals for positron emission tomography from inhibitors of mechanistic target of rapamycin (MTOR)

International audienc

Receptor for advanced glycation end products modulates oxidative stress and mitochondrial function in the soleus muscle of mice fed a high-fat diet

Accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) are implicated in the progression of pathologies associated with aging, chronic inflammation, diabetes, and cellular stress. RAGE activation is also implicated in cardiovascular complications of type 2 diabetes, such as nephropathy, retinopathy, accelerated vascular diseases, and cardiomyopathy. Studies investigating the effects of AGE/RAGE axis activation on skeletal muscle oxidative stress and metabolism are more limited. We tested whether a high-fat diet (HFD) would alter circulating AGE concentration, skeletal muscle AGE accumulation, and oxidative stress in wild-type and RAGE-deficient mice. The physiological significance of AGE/RAGE axis activation in HFD-fed mice was evaluated in terms of exercise tolerance and mitochondrial respiratory chain complex activity. HFD elicited adiposity, abnormal fat distribution, and oral glucose intolerance. HFD also induced accumulation of Nε-carboxymethyl-l-lysine, increased protein carbonyl levels, and impaired respiratory chain complex activity in soleus muscle. Ablation of RAGE had no effects on weight gain and oral glucose tolerance in HFD-fed mice. Peak aerobic capacity and mitochondrial cytochrome-c oxidase activity were restored in HFD-fed RAGE−/− mice. We concluded that RAGE signaling plays an important role in skeletal muscle homeostasis of mice under metabolic stress. Novelty HFD in mice induces accumulation of AGEs, oxidative stress, and mitochondrial dysfunction in the soleus muscle. RAGE, the multi-ligand receptor for AGEs, modulates oxidative stress and mitochondrial electron transport chain function in the soleus muscle of HFD-fed mice.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Distribution of coronary artery disease severity and risk factors in Afro-Caribbeans

SummaryBackgroundTraditional risk factors are strong predictors of the incidence of coronary artery disease (CAD), but their association with disease severity remains controversial and could differ across ethnic groups.AimsIn this study, we assessed the prevalence of cardiovascular risk factors (CRFs) in Afro-Caribbean patients with documented CAD, and sought to identify which of these factors are related to disease severity.MethodsWe retrospectively studied 420 consecutive patients with CAD. Disease severity was determined from the results of invasive coronary angiography, based on the presence or absence of multiple (two or three) diseased vessels and the myocardial jeopardy (MJ) score.ResultsIn the studied population (mean age 64.7±12.4 years), hypertension, diabetes and dyslipidaemia were the most frequent modifiable CRFs, present in 75.9, 47.8 and 37.8% of patients, respectively. Multiple logistic regression analysis showed that diabetes, male sex and personal cardiovascular history significantly increased the risk of multivessel CAD: odds ratios (ORs) of 1.53 (1.01–2.33; P=0.048), 1.61 (1.02–2.55; P=0.043) and 1.68 (1.11–2.56; P=0.015), respectively. Obesity was an independent negative predictor, with an OR of 0.48 (0.29–0.79; P=0.004). Other traditional CRFs (hypertension, dyslipidaemia, smoking, age and family history of vascular disease) were not associated with CAD severity. For high-risk lesions (MJ score ≥8), both diabetes and hypertension were independent predictors of disease severity, whereas obesity was no longer a protective factor.ConclusionDiabetes emerged as the strongest modifiable risk factor predictor of multivessel disease in Afro-Caribbean patients, whereas obesity was an independent protective factor. The underlying mechanisms of these associations should be relevant to disease prevention

A PRKAR1A Mutation Associated with Primary Pigmented Nodular Adrenocortical Disease in 12 Kindreds

CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent Cushing syndrome, can be part of Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation. OBJECTIVE:The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at two referral centers. PATIENTS: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD. RESULTS: We describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12 unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers. CONCLUSIONS: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype.This work was supported by the Groupement d’Intérêt Scientifique-Institut National de la Santé et de la Recherche Médicale Institut des Maladies Rares and the Plan Hospitalier de Recherche Clinique (AOM 02068 to the Comete Network coordinated by Professor P. F. Plouin), and in part by National Institutes of Health intramural project Z01-HD- 000642-04 (to C.A.S.).Ye