Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

BACKGROUND Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.

BACKGROUND Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish society of internal medicine.

BACKGROUND Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.

Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study.

BACKGROUND Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. METHODS The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. CONCLUSIONS Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.

Nouveautés en médecine interne hospitalière 2007: perspective des chefs de clinique [Highlights 2007 in hospital-based internal medicine: the point of view from the chief residents]

L'année 2007 a été marquée par la publication de plusieurs études internationales concernant directement le quotidien de l'interniste hospitalier. Un résumé de ces travaux ne saurait être qu'un extrait condensé et forcément subjectif d'une croissante et dynamique diversité. Au gré de leurs lectures, de leurs intérêts et de leurs interrogations, les chefs de clinique du Service de médecine interne vous proposent ainsi un parcours original revisitant les thèmes de l'insuffisance cardiaque, du diabète, de l'endocardite, de la BPCO ou de la qualité des soins. Cette variété de sujets illustre à la fois le vaste champ couvert par la médecine interne actuelle, ainsi que les nombreuses incertitudes liées à la pratique médicale moderne basée sur les preuves. In 2007, several international studies brought useful information for the daily work of internists in hospital settings. This summary is of course subjective but reflects the interests and questions of the chief residents of the Department of internal medicine who wrote this article like an original trip in medical literature. This trip will allow you to review some aspects of important fields such as heart failure, diabetes, endocarditis, COPD, and quality of care. Besides the growing diversity of the fields covered by internal medicine, these various topics underline also the uncertainty internists have to face in a practice directed towards evidence.

400 mètres haies [vainqueur] André, Colombes 20/7/19 championnat de France d'athlétisme U.S.F.S.A. [Union des Sociétés Françaises de Sports Athlétiques] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55049

Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort.

BACKGROUND Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. METHODS To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. RESULTS A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. CONCLUSION Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.

Effect of high-intensity interval exercise on lipid oxidation during postexercise recovery.

PURPOSE: The aim of this study was to examine whether lipid oxidation predominates during 3 h of postexercise recovery in high-intensity interval exercise as compared with moderate-intensity continuous exercise on a cycle ergometer in fit young men (n = 12; 24.6 +/- 0.6 yr). METHODS: The energy substrate partitioning was evaluated during and after high-intensity submaximal interval exercise (INT, 1-min intervals at 80% of maximal aerobic power output [Wmax] with an intervening 1 min of active recovery at 40% Wmax) and 60-min moderate-intensity continuous exercise at 45% of maximal oxygen uptake (C45%) as well as a time-matched resting control trial (CON). Exercise bouts were matched for mechanical work output. RESULTS: During exercise, a significantly greater contribution of CHO and a lower contribution of lipid to energy expenditure were found in INT (512.7 +/- 26.6 and 41.0 +/- 14.0 kcal, respectively) than in C45% (406.3 +/- 21.2 and 170.3 +/- 24.0 kcal, respectively; P < 0.001) despite similar overall energy expenditure in both exercise trials (P = 0.13). During recovery, there were no significant differences between INT and C45% in substrate turnover and oxidation (P > 0.05). On the other hand, the mean contribution of lipids to energy yield was significantly higher after exercise trials (C45% = 61.3 +/- 4.2 kcal; INT = 66.7 +/- 4.7 kcal) than after CON (51.5 +/- 3.4 kcal; P < 0.05). CONCLUSIONS: These findings show that lipid oxidation during postexercise recovery was increased by a similar amount on two isoenergetic exercise bouts of different forms and intensities compared with the time-matched no-exercise control trial.

Validity of four short physical activity questionnaires in middle-aged persons.

PURPOSE: Self-administered questionnaires continue to be the most widely used type of physical activity assessment in epidemiological studies. However, test-retest reliability and validity of physical activity questionnaires have to be determined. In this study, three short physical activity questionnaires already used in Switzerland and the International Physical Activity Questionnaire (IPAQ) were validated. METHODS: Test-retest reliability was assessed by repeated administration of all questionnaires within 3 wk in 178 volunteers (77 women, 46.1+/-14.8 yr; 101 men 46.8+/-13.2 yr). Validity of categorical and continuous data was studied in a subsample of 35 persons in relation to 7-d accelerometer readings, percent body fat, and cardiorespiratory fitness. RESULTS: Reliability was fair to good with a Spearman correlation coefficient range of 0.43-0.68 for measures of continuous data and moderate to fair with Kappa values between 0.32 and 0.46 for dichotomous measures active/inactive. Total physical activity reported in the IPAQ and the Office in Motion Questionnaire (OIMQ) correlated with accelerometry readings (r=0.39 and 0.44, respectively). In contrast, correlations of self-reported physical data with percent body fat and cardiorespiratory fitness were low (r=-0.26-0.29). Participants categorized as active by the Swiss HEPA Survey 1999 instrument (HEPA99) accumulated significantly more days of the recommended physical activities than their inactive counterparts (4.4 and 2.7 d.wk, respectively, P<0.05). However, compared with accelerometer data, vigorous physical activities were overreported in investigated questionnaires. CONCLUSION: Collecting valid data on physical activity remains a challenging issue for questionnaire surveys. The IPAQ and the three other questionnaires are characterized to inform decisions about their appropriate use.

RED BLOOD CELL MICROPARTICLES: ROLE IN TRANSFUSION MEDICINE?

RésuméLes microparticules sont des vésicules phospholipidiques de moins d‟un micromètre relâchées dans le sang par différents types cellulaires, comme les cellules endothéliales, les plaquettes ou encore les globules blancs et rouges. Elles sont bioactives et impliquées dans de nombreux processus physiologiques incluant l‟hémostase. De plus, un nombre élevé de microparticules circulantes dans le sang a été observé dans différentes pathologies.Dans le domaine de la transfusion, les microparticules de globules rouges ont été détectées dans les concentrés érythrocytaires. Le but de cette recherche était de caractériser les microparticules de globules rouges et d‟évaluer si ces dernières avaient un rôle en transfusion. Pour ce faire, une approche globale utilisant différentes techniques comme la cytométrie de flux, la protéomique, la microscopie ainsi que des tests d‟hémostase de routines, a été adoptée.Le présent travail de thèse a démontré que les microparticules de globules rouges s‟accumulent dans les concentrés érythrocytaires pendant le stockage. Leur bioactivité a été démontrée de part leur rôle actif dans le processus de la coagulation. En effet, lors de test de génération de thrombine, elles peuvent non seulement supporter ce processus de coagulation, mais aussi le déclencher par un mécanisme inconnu sous certaines circonstances. Les microparticules de globules rouges présentent aussi des antigènes de groupes sanguins à leur surface, toutefois, leur implication potentielle dans l‟induction d‟une réponse immunitaire n‟est pas connue. Bien que le mécanisme de formation et d‟émissions des microparticules par les globules rouges ne soit pas complètement élucidé, il a été démontré qu‟elles n‟ont pas toutes le même contenu protéique et donc qu‟elles pourraient avoir des fonctions différentes.Au vu des résultats, notamment par leur implication dans la coagulation, il est fort probable que la présence de microparticules puisse affecter la qualité des produits sanguins, et causer des réactions transfusionnelles.

Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained. The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids.