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1.
Diabetes Care ; 44(3): 839-843, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33361146

RESUMO

OBJECTIVE: To investigate the impact of coronavirus disease 2019 lockdown on glycemic control and associated factors in people living with type 1 diabetes. RESEARCH DESIGN AND METHODS: An observational evaluation from a self-reported questionnaire on behavioral changes and glycemic information from flash glucose monitoring (FGM) during the lockdown in 1,378 individuals living with type 1 diabetes who used a French dedicated nationwide web application (CoviDIAB). RESULTS: The main outcome was the change of the mean glucose level 2 months before and 1 month after the lockdown. We found that mean glucose improved from 9.1 ± 1.7 mmol/L to 8.7 ± 1.7 mmol/L (P < 0.001). Factors associated with better glycemic control were a decrease of alcohol consumption (odds ratio [OR] 1.75 [95% CI 1.04-2.94]), an increase in the frequency of FGM scans (OR 1.48 [1.04-2.10]) and in the number of hypoglycemia events (OR 1.67 [1.13-2.46]), and an easier diabetes control perception (OR 1.71 [1.18-2.49]). CONCLUSIONS: Our findings suggest that lockdown has a positive impact on glycemic control in people with type 1 diabetes.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Diabetes Mellitus Tipo 1/terapia , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/epidemiologia , Humanos , Hipoglicemia , Pessoa de Meia-Idade , SARS-CoV-2
2.
J Pediatr ; 186: 64-71.e1, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28283258

RESUMO

OBJECTIVE: To identify body mass index (BMI) trajectories from birth to age 10 years and to assess their association with child and parental characteristics and with adult nutritional status and metabolic risk factors. STUDY DESIGN: Retrospective cohort study with 1188 subjects aged 20-60 years. Childhood growth was assessed using measured weight and height data collected retrospectively from health booklets, which also provided information on gestational age, birth weight, and early nutrition. Height, weight, waist circumference, fasting blood glucose, lipids profile, and blood pressure were measured at adulthood. Participants self-reported parental silhouette based on a 9-figural scale. Group-based modeling was applied to identify BMI trajectories. Associations were assessed using ANOVA and multiple logistic regression. RESULTS: Five growth trajectories following or crossing BMI percentiles emerged: stable-25th (15.3% of the sample), stable-50th (35.9%), stable-75th (28.0%), ascending-75th (19.2%), and ascending-obesity (1.6%). Overall, associated factors from early life were mother's corpulence (higher in the ascending-obesity group), gestational age (higher in the stable-50th, stable-75th, and in the ascending-obesity groups), and birth weight (higher in the ascending-obesity group) (all P < .05). Childhood trajectories were associated with adult BMI and waist circumference (higher in the stable-75th and in the ascending groups) (all P < .0001). CONCLUSIONS: This study shows heterogeneity in patterns of growth trajectories. Specific trajectories were associated with greater BMI and waist circumference during adulthood. Monitoring growth trajectories may improve chronic disease prevention.


Assuntos
Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Desenvolvimento Infantil/fisiologia , Adulto , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Retrospectivos , Fatores de Risco , Aumento de Peso , Adulto Jovem
3.
BMC Public Health ; 17(1): 86, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28095815

RESUMO

BACKGROUND: In aggregate studies, ecological indices are used to study the influence of socioeconomic status on health. Their main limitation is ecological bias. This study assesses the misclassification of individual socioeconomic status in seven ecological indices. METHODS: Individual socioeconomic data for a random sample of 10,000 persons came from periodic health examinations conducted in 2006 in 11 French departments. Geographical data came from the 2007 census at the lowest geographical level available in France. The Receiver Operating Characteristics (ROC) curves, the areas under the curves (AUC) for each individual variable, and the distribution of deprived and non-deprived persons in quintiles of each aggregate score were analyzed. RESULTS: The aggregate indices studied are quite good "proxies" for individual deprivation (AUC close to 0.7), and they have similar performance. The indices are more efficient at measuring individual income than education or occupational category and are suitable for measuring of deprivation but not affluence. CONCLUSIONS: The study inventoried the aggregate indices available in France and evaluated their assessment of individual SES.


Assuntos
Viés , Disparidades nos Níveis de Saúde , Indicadores Básicos de Saúde , Pobreza , Classe Social , Adulto , Censos , Feminino , França , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Fatores Socioeconômicos
4.
Presse Med ; 45(6 Pt 1): e145-56, 2016 Jun.
Artigo em Francês | MEDLINE | ID: mdl-27234900

RESUMO

AIMS: To describe cardiovascular risk factors and metabolic disturbances in a French population including shift workers and study whether possible changes were noticeable after non-shift to shift work transition within the last five years. METHODS: The study population included 4764 attendees of two health examinations (5 years apart), between January 1996 and October 2008, in 11 health examination centres. Clinical, biological and metabolic factors together with their changes over a five-year period were compared between attendees who kept a non-shift daytime job, those who kept working shift and those who switched from non-shift daytime to shift work over the last 5 years. RESULTS: At baseline, working shift was, independently of lifestyle or BMI, significantly related to more elevated plasma triglycerides (ß=0.04, P=0.05) and rate of hypertriglyceridemia (ß=0.27, P=0.01), lower plasma HDL-C levels (ß=-2.03, P=0.006) and less hypertension (ß=-0.25, P=0.01) compared to non-shift daytime work. In men, a slightly more elevated yet non significant proportion of hypertriglyceridemia was observed with the transition from non-shift daytime to shift work within the last 5 years in comparison to men who kept a non-shift daytime job (13.9% vs. 11.0% P=0.17). CONCLUSION: Our results are in agreement with previous studies showing a deleterious effect of shift work on lipid metabolism. In our population, triglycerides and HDL-C levels were the main parameters negatively influenced by shift work. Consequently, a regular biological monitoring together with the promotion of healthy behaviours should be provided to shift workers before negative consequences of working shift become noticeable.


Assuntos
Doenças Cardiovasculares/epidemiologia , Dislipidemias/epidemiologia , Pessoal de Saúde , Doenças Profissionais/epidemiologia , Tolerância ao Trabalho Programado , Adulto , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco
5.
Sante Publique ; 28(4): 451-460, 2016 Oct 19.
Artigo em Francês | MEDLINE | ID: mdl-28155749

RESUMO

Aims: To set up physical activity promotion workshops in health centres to help people with a sedentary lifestyle achieve an adequate level of physical activity. Methods: This health programme, called 'Bougeons Notre Santé' (Let's move our health) has been implemented since 2006 by four health centres in the Pays de la Loire region, in France. This article describes implementation of the programme, its feasibility, how it can be integrated into a global preventive approach and its outcomes on promoting more physical activity. The "Let's move our health!" programme comprises four group meetings with participants over a period of several months. At these meetings, participants discuss, exchange and monitor their qualitative and quantitative level of physical activity. Realistic and achievable goals are set in consultation with each participant in relation to their personal circumstances and are monitored with a pedometer and a follow-up diary. Support on healthy eating is also provided. This programme is an opportunity to promote health and refer participants to existing local resources. Results: Forty groups, comprising a total of 275 people, have participated in the programme since 2006. After the four meetings, participants had increased their physical activity level by an average of 723 steps per day and 85% reported that they had changed their eating habits. Conclusion: This health promotion programme is feasible and effective: an increase in the physical activity of participants was observed, together with a favourable impact on perceived health, well-being and social links. These workshops are integrated into a network of associations and institutional partners and could be implemented by similar social or health organisations.


Assuntos
Educação , Exercício Físico/fisiologia , Exercício Físico/psicologia , Promoção da Saúde , Motivação , Adulto , Idoso , Educação/organização & administração , Educação/estatística & dados numéricos , Eficiência Organizacional , Estudos de Viabilidade , Feminino , França/epidemiologia , Processos Grupais , Implementação de Plano de Saúde/métodos , Implementação de Plano de Saúde/organização & administração , Promoção da Saúde/métodos , Promoção da Saúde/organização & administração , Humanos , Masculino , Pessoa de Meia-Idade , Serviços Preventivos de Saúde/métodos , Serviços Preventivos de Saúde/organização & administração , Estudos Retrospectivos , Adulto Jovem
6.
Presse Med ; 44(5): e191-201, 2015 May.
Artigo em Francês | MEDLINE | ID: mdl-25704803

RESUMO

AIM: Shift work, especially including a night shift, is associated with degradation of physical, social and psychosocial health as well as poor well-being. Food imbalance and low physical activity contributed to the negative effects on health. Our objective was to promote a healthier nutritional behaviour according to the French national nutrition and health program recommendations (PNNS). METHODS: A one-year nutritional intervention with personalised dietetic counselling was proposed to 235 shift workers with night shift who came for a health prevention exam in one of the centres of the Institut Inter-Régional pour la Santé between 2009 and 2011. The intervention was three dietary interviews: at baseline with definition of goal setting, at 3 months for advice and support and at one-year for the evaluation. At 6 months, a personalised reminder letter was send. Compliance with the PNNS recommendations and level of physical activity were evaluated at baseline and at one-year by a self-administered questionnaire. Changes between baseline and follow-up were compared by paired t-tests or McNemar-tests. RESULTS: The rate of follow-up was 57.4%. At the end of the study, subjects improved their compliance with PNNS guidelines concerning sweetened products (P<0.001), water (P=0.02) and salt (P=0.05), increased their leisure physical activity (P=0.001) and decreased their daily energy intakes (P<0.001). CONCLUSION: A structured intervention can improve nutritional behaviours of shift workers. This intervention enabled to inform and alert on the risk related to this work schedule and promote better nutritional behaviours.


Assuntos
Ritmo Circadiano , Comportamento Alimentar/fisiologia , Promoção da Saúde , Trabalho/fisiologia , Adulto , Aconselhamento , Dieta , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Inquéritos e Questionários , Tolerância ao Trabalho Programado , Adulto Jovem
7.
Int J Cancer ; 136(8): 1827-34, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25195670

RESUMO

The aim of this study was to compare the seasonal variation in performance of a faecal immunochemical test for haemoglobin (FIT) and a guaiac test (gFOBT) for colorectal cancer screening. From June 2009 to May 2011, 18,290 screening participants (50-74 years old) performed OC-SENSOR quantitative FIT (1 sample) and Hemoccult II gFOBT (3 stool samples with 2 spots/sample). Referral for colonoscopy required a minimum of one positive spot (gFOBT), or a positive FIT [cut-off 150 ng haemoglobin/mL buffer (i.e. 30 µg haemoglobin/g feces)]. The performance of tests for detection of advanced neoplasia was compared according to seasons using Receiver Operating Characteristics (ROC) curves, at various FIT cut-off values. The positivity rate of FIT was significantly lower in the summer compared with other seasons (2.3% versus 3.0%, p = 0.03), whilst the positivity rate of gFOBT increased in the autumn (1.8% versus 1.5%, p = 0.11). FIT was clinically more effective than gFOBT over the four season-specific ROC curves. At the cut-off concentration used in the study, the season-specific FIT/gFOBT ratios for true positive rates were: 2.8 (Autumn), 2.5 (Winter), 3.0 (Spring), 3.7 (Summer), and for false positive rates: 1.2 (Autumn), 1.5 (Winter), 1.8 (Spring), 0.9 (Summer). Therefore, in this study with this cut-off concentration and in spite of lower positivity rate in summer, the seasonal variations of performance of OC-SENSOR FIT led to improved gain in specificity in the summer, without a decrease in gain in sensitivity compared with gFOBT.


Assuntos
Neoplasias Colorretais/diagnóstico , Fezes/química , Guaiaco , Idoso , Colonoscopia/métodos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Imunoensaio/métodos , Imunoquímica/métodos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Sangue Oculto , Curva ROC , Estações do Ano , Sensibilidade e Especificidade
8.
Ann Biol Clin (Paris) ; 72(5): 561-81, 2014.
Artigo em Francês | MEDLINE | ID: mdl-25336130

RESUMO

The full blood count (FBC) is the most prescribed laboratory test in France. Due to the lack of data, there is a great variability in reference values of the FBC, between medical laboratories. The aim of this work was to provide normal reference values for FBC in adults. These normal values were defined in a population of 33 258 healthy adults, 19 612 men and 13 646 women. These values were determined after excluding subjects having conditions in order to modify, either directly or indirectly, FBC parameters. For each parameter, we provide results for values of standard parameters, by sex and age, from 16 to 69 years. In addition, we present FBC values from a population of 339 subjects aged over 69 years with no comorbidities. These normal values are proposed to be used in everyday practice. They make it possible to distinguish, without ambiguity, a normal situation from a pathological situation. Moreover, they can be applied to the entire metropolitan France.


Assuntos
Contagem de Células Sanguíneas , Adolescente , Adulto , Idoso , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
9.
J Clin Endocrinol Metab ; 99(12): 4656-63, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25202818

RESUMO

CONTEXT: Vasopressin plays a central role in water homeostasis but it has also been recognized to be associated with adverse effects in several chronic diseases. Recently, copeptin has been increasingly used as a surrogate for vasopressin, as they are co-secreted, and copeptin is easier to measure. However, the relationship between plasma concentrations of copeptin (P(cop)) and vasopressin (P(vp)) has only been studied in relatively small numbers of selected people. OBJECTIVE: This study sought to evaluate the relationship between P(vp) and P(cop) in a community-based population and in people with chronic kidney disease (CKD). DESIGN, SETTING, AND PARTICIPANTS: P(vp), P(cop), and urinary osmolarity (Uosm) were compared in 500 participants of the DESIR study, and in 83 ambulatory people with CKD. RESULTS: Median [interquartile range] of P(cop) and P(vp) in the DESIR study were 4.13 [3.58] pmol/L and 0.92 [1.93] pmol/L, respectively. Log-transformed P(cop) and P(vp) concentrations correlated significantly and positively (r = 0.686, P < .001) and they correlated inversely with estimated U(osm) (P < .001). Copeptin explained only approximately half of the vasopressin variation. In CKD, P(cop) and P(vp) both increased with decreasing estimated glomerular filtration rate (eGFR), but P(cop) increased much faster than P(vp). The P(cop)/P(vp) ratios in the lower and upper quintile groups of eGFR were 14.3 [18.3] and 5.3 [4.5], P < .001, respectively. CONCLUSIONS: This study in a normal population, the largest ever with measurements of both peptides, shows that copeptin and vasopressin concentrations correlated well. But their relationship is distorted in CKD, suggesting that the peptide clearances differ when the renal function is impaired.


Assuntos
Glicopeptídeos/sangue , Insuficiência Renal Crônica/sangue , Vasopressinas/sangue , Adulto , Idoso , Ingestão de Líquidos , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar
10.
Diabetologia ; 57(8): 1601-10, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24893864

RESUMO

AIMS/HYPOTHESIS: Genome-wide association studies have firmly established 65 independent European-derived loci associated with type 2 diabetes and 36 loci contributing to variations in fasting plasma glucose (FPG). Using individual data from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study, we evaluated the contribution of three genetic risk scores (GRS) to variations in metabolic traits, and to the incidence and prevalence of impaired fasting glycaemia (IFG) and type 2 diabetes. METHODS: Three GRS (GRS-1, 65 type 2 diabetes-associated single nucleotide polymorphisms [SNPs]; GRS-2, GRS-1 combined with 24 FPG-raising SNPs; and GRS-3, FPG-raising SNPs alone) were analysed in 4,075 DESIR study participants. GRS-mediated effects on longitudinal variations in quantitative traits were assessed in 3,927 nondiabetic individuals using multivariate linear mixed models, and on the incidence and prevalence of hyperglycaemia at 9 years using Cox and logistic regression models. The contribution of each GRS to risk prediction was evaluated using the C-statistic and net reclassification improvement (NRI) analysis. RESULTS: The two most inclusive GRS were significantly associated with increased FPG (ß = 0.0011 mmol/l per year per risk allele, p GRS-1 = 8.2 × 10(-5) and p GRS-2 = 6.0 × 10(-6)), increased incidence of IFG and type 2 diabetes (per allele: HR GRS-1 1.03, p = 4.3 × 10(-9) and HR GRS-2 1.04, p = 1.0 × 10(-16)), and the 9 year prevalence (OR GRS-1 1.13 [95% CI 1.10, 1.17], p = 1.9 × 10(-14) for type 2 diabetes only; OR GRS-2 1.07 [95% CI 1.05, 1.08], p = 7.8 × 10(-25), for IFG and type 2 diabetes). No significant interaction was found between GRS-1 or GRS-2 and potential confounding factors. Each GRS yielded a modest, but significant, improvement in overall reclassification rates (NRI GRS-1 17.3%, p = 6.6 × 10(-7); NRI GRS-2 17.6%, p = 4.2 × 10(-7); NRI GRS-3 13.1%, p = 1.7 × 10(-4)). CONCLUSIONS/INTERPRETATION: Polygenic scores based on combined genetic information from type 2 diabetes risk and FPG variation contribute to discriminating middle-aged individuals at risk of developing type 2 diabetes in a general population.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Homeostase/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Diabetes Mellitus Tipo 2/sangue , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , População Branca/genética
11.
J Clin Pathol ; 67(4): 341-4, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24170208

RESUMO

AIMS: To determine full blood count (FBC) normal reference values for adults. METHODS: FBC normal values for healthy adults were defined, after establishing preanalytical conditions, in a population of 33 258 subjects, 19 612 men and 13 646 women. The values were established after excluding from this population all people having conditions liable to modify, directly or indirectly, FBC parameters. RESULTS: Results for values of standard parameters are provided in detail for each parameter, by sex and by age group from 16 to 69 years of age. In addition, we present FBC values from a population of 339 subjects aged over 69 years with no comorbidities. CONCLUSIONS: These normal values are proposed for use in everyday practice. They make it possible to distinguish, without ambiguity, a normal situation from a pathological situation. Moreover, they might be used over all mainland France.


Assuntos
Contagem de Células Sanguíneas/normas , Adolescente , Adulto , Idoso , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
12.
Diabetologia ; 57(1): 30-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24065153

RESUMO

AIMS/HYPOTHESIS: The relationships between smoking and glycaemic variables have not been well explored. We compared HbA1c, fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex- and never-smokers. METHODS: This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies. Means of three glycaemic variables in current, ex- and never-smokers were modelled by linear regression, with study as a random factor. The I (2) statistic was used to evaluate heterogeneity among studies. RESULTS: HbA1c was 0.10% (95% CI 0.08, 0.12) (1.1 mmol/mol [0.9, 1.3]) higher in current smokers and 0.03% (0.01, 0.05) (0.3 mmol/mol [0.1, 0.5]) higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current and never-smokers (-0.004 mmol/l [-0.03, 0.02]) but FPG was higher in ex-smokers (0.12 mmol/l [0.09, 0.14]). In comparison with never-smokers, 2H-PG was lower (-0.44 mmol/l [-0.52, -0.37]) in current smokers, with no difference for ex-smokers (0.02 mmol/l [-0.06, 0.09]). There was a large and unexplained heterogeneity among studies, with I (2) always above 50%; I (2) was little changed after stratification by sex and adjustment for age and BMI. In this study population, current smokers had a prevalence of diabetes that was 1.30% higher as screened by HbA1c and 0.52% lower as screened by 2H-PG, in comparison with never-smokers. CONCLUSION/INTERPRETATION: Across this heterogeneous group of studies, current smokers had a higher HbA1c and lower 2H-PG than never-smokers. This will affect the chances of smokers being diagnosed with diabetes.


Assuntos
Glicemia/metabolismo , Jejum/sangue , Hemoglobinas Glicadas/metabolismo , Fumar/sangue , Fumar/metabolismo , Humanos
13.
Eur J Public Health ; 24(4): 585-94, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24068546

RESUMO

BACKGROUND: Association between deprivation and health is well established, particularly among unemployed or fixed-term contract or temporary contract subjects. This study aimed to assess if this relationship existed as well in full-time permanent workers. METHODS: Biometrical, biological, behavioural and psychosocial health risk indicators and an individual deprivation score, the Evaluation of Precarity and Inequalities in Health Examination Centres score, were recorded from January 2007 to June 2008, in 34 905 full-time permanent workers aged 18-70 years, all volunteers for a free health examination. Comparisons of the behavioural, metabolic, cardiovascular and health risk indicators between quintiles of the deprivation score with adjustments on age and socioeconomic categories were made by covariance analysis or logistic regression. RESULTS: For both genders, degradation of nutritional behaviours, metabolic and cardiovascular indicators and health appeared gradually with deprivation, even for deprivation score usually considered as an insignificant value. The absence of only one social support or one social network was associated with a degradation of health. Full-time permanent workers with the poorest health risk indicators had more frequent social exclusion signs. These results were independent of socioeconomic categories and age. CONCLUSION: Understanding how deprivation influences health status may lead to more effective interventions to reduce social inequalities in health. The deprivation Evaluation of Precarity and Inequalities in Health Examination Centres score is a relevant tool to detect subjects who could benefit from preventive interventions. Our findings suggest that this deprivation score should be used as a health risk indicator even in full-time permanent workers. Assessing deprivation is useful to design and evaluate specific intervention programmes.


Assuntos
Emprego/estatística & dados numéricos , Nível de Saúde , Carência Psicossocial , Adolescente , Adulto , Idoso , Escolaridade , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Psicologia , Recreação , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
14.
Diabetologia ; 56(11): 2414-23, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23942764

RESUMO

AIMS/HYPOTHESIS: The relationship between insulin secretion and the incidence of hypertension has not been well characterised. We hypothesised that both a parental history of diabetes and TCF7L2 rs7903146 polymorphism, which increases susceptibility to diabetes because of impaired beta cell function, are associated with incident hypertension. In a separate cohort, we assessed whether low insulin secretion is related to incident hypertension. METHODS: Nine year incident hypertension was studied in 2,391 normotensive participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. The relationship between insulin secretion and 3 year incident hypertension was investigated in 1,047 non-diabetic, normotensive individuals from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort. Insulin secretion during OGTT was expressed in relation to the degree of insulin resistance, as assessed by a hyperinsulinaemic-euglycaemic clamp. RESULTS: In the DESIR cohort, a parental history of diabetes and the TCF7L2 at-risk variant were both associated with hypertension incidence at year 9, independently of waist circumference, BP, fasting glucose, insulin levels and HOMA-IR at inclusion (p = 0.02 for parental history, p = 0.006 for TCF7L2). In the RISC cohort, a lower insulin secretion rate during the OGTT at baseline was associated with both higher BP and a greater risk of hypertension at year 3. This inverse correlation between the insulin secretion rate and incident hypertension persisted after controlling for baseline insulin resistance, glycaemia and BP (p = 0.007). CONCLUSIONS/INTERPRETATION: Parental history of diabetes, TCF7L2 rs7903146 polymorphism and a reduced insulin secretion rate were consistently associated with incident hypertension. A low insulin secretion rate might be a new risk factor for incident hypertension, beyond insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão/epidemiologia , Hipertensão/metabolismo , Insulina/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adulto , Idoso , Feminino , Humanos , Hipertensão/genética , Secreção de Insulina , Masculino , Pessoa de Meia-Idade
15.
Nat Genet ; 45(9): 1040-3, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23852171

RESUMO

Large chromosomal clonal mosaic events (CMEs) have been suggested to be linked to aging and to predict cancer. Type 2 diabetes (T2D) has been conceptualized as an accelerated-aging disease and is associated with higher prevalence of cancers. Here we aimed to assess the association between T2D and CME occurrence in blood. We evaluated the presence of CMEs in 7,659 individuals (including 2,208 with T2D) using DNA arrays. A significant association between CME occurrence and T2D was found (odds ratio (OR) = 5.3; P = 5.1 × 10(-5)) and was stronger when we only considered non-obese individuals with T2D (OR = 5.6; P = 4.9 × 10(-5)). Notably, CME carriers with T2D had higher prevalence of vascular complications than non-carriers with T2D (71.4% versus 37.1%, respectively; P = 7.7 × 10(-4)). In CME carriers, we found an increase in the percentage of abnormal cells over 6 years (P = 8.60 × 10(-3)). In conclusion, given the increased risk of cancer in CME carriers, our results may have profound clinical implications in patients with severe T2D.


Assuntos
Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Estudos de Associação Genética , Mosaicismo , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Aberrações Cromossômicas , Mapeamento Cromossômico , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos
16.
Nat Genet ; 45(9): 1044-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23872634

RESUMO

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10(-68); rs9388451, P = 5.1 × 10(-17)) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10(-14)). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (Ptrend = 6.1 × 10(-81)). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Síndrome de Brugada/complicações , Síndrome de Brugada/genética , Morte Súbita Cardíaca/etiologia , Variação Genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Proteínas Repressoras/genética , Alelos , Animais , Estudos de Casos e Controles , Cromossomos Humanos Par 3 , Cromossomos Humanos Par 6 , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos , Camundongos Knockout , Razão de Chances , Polimorfismo de Nucleotídeo Único , Canais de Sódio/genética , Canais de Sódio/metabolismo
17.
J Clin Invest ; 123(7): 3037-41, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23778136

RESUMO

Sim1 haploinsufficiency in mice induces hyperphagic obesity and developmental abnormalities of the brain. In humans, abnormalities in chromosome 6q16, a region that includes SIM1, were reported in obese children with a Prader-Willi-like syndrome; however, SIM1 involvement in obesity has never been conclusively demonstrated. Here, SIM1 was sequenced in 44 children with Prader-Willi-like syndrome features, 198 children with severe early-onset obesity, 568 morbidly obese adults, and 383 controls. We identified 4 rare variants (p.I128T, p.Q152E, p.R581G, and p.T714A) in 4 children with Prader-Willi-like syndrome features (including severe obesity) and 4 other rare variants (p.T46R, p.E62K, p.H323Y, and p.D740H) in 7 morbidly obese adults. By assessing the carriers' relatives, we found a significant contribution of SIM1 rare variants to intra-family risk for obesity. We then assessed functional effects of the 8 substitutions on SIM1 transcriptional activities in stable cell lines using luciferase gene reporter assays. Three mutations showed strong loss-of-function effects (p.T46R, p.H323Y, and p.T714A) and were associated with high intra-family risk for obesity, while the variants with mild or no effects on SIM1 activity were not associated with obesity within families. Our genetic and functional studies demonstrate a firm link between SIM1 loss of function and severe obesity associated with, or independent of, Prader-Willi-like features.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Mutação de Sentido Incorreto , Obesidade Mórbida/genética , Síndrome de Prader-Willi/genética , Proteínas Repressoras/genética , Adulto , Estudos de Casos e Controles , Pré-Escolar , Análise Mutacional de DNA , Feminino , Expressão Gênica , Frequência do Gene , Genes Reporter , Estudos de Associação Genética , Células HEK293 , Humanos , Lactente , Luciferases/biossíntese , Luciferases/genética , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Ativação Transcricional , Adulto Jovem
18.
J Mol Med (Berl) ; 91(9): 1109-15, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23640704

RESUMO

We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (ß = 0.180 [0.022-0.339], P value = 0.0258 and ß = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (ß = 0.151 [-0.006 to 0.309], P value = 0.0591 and ß = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Obesidade/genética , Lanches/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Razão de Chances , Fenótipo , Polimorfismo de Nucleotídeo Único , População Branca/genética , Adulto Jovem
19.
Metabolism ; 62(9): 1323-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23647908

RESUMO

OBJECTIVE: The T allele of a functional polymorphism (rs4988235: LCT-13910 C>T), close to the lactase gene, correlates with lactase persistence (LP) in adults. The LP genotype (TT+TC) has been associated with a higher BMI in European populations in cross-sectional studies. In the French D.E.S.I.R. cohort, a high consumption of dairy products was associated with a lower body weight gain over 9-years, and with a lower incidence of high plasma glucose levels and/or the metabolic syndrome. Our aim was to test in this study, the association of rs4988235 with BMI and related metabolic diseases, in interaction with dairy product consumption. METHODS: Among 5212 subjects from D.E.S.I.R., 3575 Caucasians born in mainland France were genotyped and followed over 9years. RESULTS: Those with the LP genotype (frequency: 78.5%) had a higher dairy product consumption, at inclusion and at year-9 (P<0.001). They also had a higher BMI at both time points (difference=0.3kg/m(2), P=0.05), but this effect was restricted to medium/high dairy product consumers (difference=0.5kg/m(2), P=0.006). This genotype was also associated with the metabolic syndrome (IDF definition), but this association disappeared after adjustment for BMI. In the whole population, the C allele was associated with a higher prevalence of impaired fasting glycemia and/or type 2 diabetes. CONCLUSIONS: The lactase persistence genotype was shown to be associated with a higher BMI in a longitudinal study, mainly in those consuming high amounts of dairy products. The association of the C allele, responsible for lactase non-persistence, with the risk of hyperglycemia needs to be replicated.


Assuntos
Índice de Massa Corporal , Laticínios , Lactase/genética , Adulto , Glicemia/análise , Estudos de Coortes , Diabetes Mellitus Tipo 2/etiologia , Feminino , França , Genótipo , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade
20.
Presse Med ; 42(7-8): e245-58, 2013.
Artigo em Francês | MEDLINE | ID: mdl-23490635

RESUMO

OBJECTIVES: To study the reproducibility and validity of a French self-administered questionnaire (NAQAPNNS) evaluating the adequation of a subject with the French national nutrition and health program recommendations. METHODS: The reproducibility was estimated by weighted kappa in 48 subjects working in the administrative departments of the head office of the Institut Inter Régional pour la Santé in Tours aged from 21 to 63 years who filled the questionnaire NAQAPNNS twice with a two weeks interval. The validity was assessed in 524 hyperglycaemic subjects (fasting plasma glucose between 1.10g/l and 1.25g/l) aged from 25 to 70 years against a seven-day dietary recall using the Kruskall-Wallis test. Agreement between self-administration of the questionnaire and dietetic interview was evaluated by weighted kappa. RESULTS: The reproducibility was "good" (kappa≥0.67) except for recommendations on breads, cereals, potatoes and legumes (kappa=0.50) and sweetened foods consumption (kappa=0.54) which showed only "satisfactory" reproducibility. For each recommendation, subjects who reached it had dietary intakes closer to dietary references intakes (P<0.03). The agreement between self-administration and dietetic interview was "good" (kappa≥0.63) except for recommendations on added fats (kappa=0.41) and salt (kappa=0.50) consumption which were only "satisfactory". DISCUSSION: The NAQAPNNS questionnaire is a consistent and reproducible tool to evaluate adequation of a subject with French national nutritional recommendations. CONCLUSION: The self-administered questionnaire NAQAPNNS can be used in clinical practice or in epidemiological studies to detect subjects with a food imbalance and needing specific care.


Assuntos
Comportamento Alimentar , Fidelidade a Diretrizes/estatística & dados numéricos , Programas Nacionais de Saúde/estatística & dados numéricos , Estado Nutricional , Inquéritos e Questionários/normas , Adulto , Idoso , Feminino , França , Humanos , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
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