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Biomedical subjects

Serge Hercberg

Publications and source records attributed to Serge Hercberg.

At least 19 recordsLinked to original sources

The relationship between food intake and outdoor temperature in a longitudinal study: a public health perspective in the context of global warming.

BACKGROUND: Climate change affects human health and nutrition. Rising temperatures may significantly impact diets, but research on their influence on dietary habits in large populations remains limited. OBJECTIVES: We aimed to study the link between outdoor temperature and energy-adjusted food consumption across profiles in a longitudinal study. METHODS: This study included 100,851 participants from the NutriNet-Santé study (2009-2023) with 1,716,046 24-h dietary records linked to daily maximum outdoor temperature at the residence, from the nearest Météo-France station. Associations were analyzed using linear mixed models with interactions tested for sex and 6 socioeconomic profiles (employees, privileged, intermediate, young, disadvantaged, and retirees) derived from clustering. RESULTS: Across all subgroups, higher outdoor temperature was associated with higher consumption of fruits, vegetables, processed meats, sweet products, water, alcoholic beverages, and sugar-sweetened beverages, whereas consumption of red meat, pulses, and dairy products decreased. From 25°C to 35°C, the increase in alcohol consumption with temperature was more pronounced in males {150 g/d [95% confidence interval (CI): 147 g/d, 153 g/d] to 166 g/d [95% CI: 162 g/d, 171 g/d], +11%} than in females [101 g/d (95% CI: 98 g/d, 103 g/d) to 107 g/d (95% CI: 104 g/d, 109 g/d), +6%]. Across socioeconomic profiles, changes shared similar directions, but some trends were more marked, notably for alcoholic beverages among employees (95% CI: 114 g/d, 130 g/d; +14%) and sugar-sweetened beverages in young (95% CI: 56 g/d, 72 g/d; +29%). Consumption of fruits increased more modestly in the young (95% CI: 227 g/d, 248 g/d; +9%) than in employees (95% CI: 194 g/d, 227 g/d; +17%). These changes, although variable in magnitude, were not accompanied by substantial modifications in energy intake or overall diet quality scores. CONCLUSIONS: These results emphasize the importance of targeted prevention messages when temperatures exceed 25°C, especially concerning alcoholic and sugar-sweetened beverages, and offer insight into potential long-term food consumption patterns (beyond seasonal changes) in the context of global warming.

Humans↗

Association between leisure-time physical activity and health-related quality of life changes over time.

OBJECTIVE: This study aimed to assess whether changes in leisure-time physical activity over 3 years are associated with changes in health-related quality of life. METHOD: Among the adults enrolled in the Supplementation en Vitamines et Minéraux Antioxidants study in France, 3891 completed the Modifiable Activity Questionnaire to assess leisure-time physical activity and the Medical Outcomes Study 36-item Short-Form to assess health-related quality of life in 1998 and 2001. Multivariate analyses involving logistic and linear regressions determined the association between changes in leisure-time physical activity and changes in health-related quality of life. RESULTS: Over 3 years, increased leisure-time physical activity was associated with high scores in health-related quality of life dimensions: physical functioning, mental health, vitality for both sexes as well as social functioning for women only. An increase of 1 h per week of leisure-time physical activity was associated with a 0.17- and 0.39-point increase in the vitality dimension in men and women, respectively. The mental component score was also increased in women increasing their leisure-time physical activity. CONCLUSION: The long-term association between leisure-time physical activity and health-related quality of life changes is limited and has little clinical significance, especially for men and for the physical health-related quality of life dimensions. The long-term association needs to be further explored before formulating public health recommendations.

Adult↗

No contribution of angiotensin-converting enzyme (ACE) gene variants to severe obesity: a model for comprehensive case/control and quantitative cladistic analysis of ACE in human diseases.

Candidate gene analyses are often inconclusive owing to genetic or phenotypic heterogeneity, low statistical power, selection of nonfunctional SNPs, and inadequate statistical analysis of the genetic architecture. Angiotensin-converting enzyme (ACE) is involved in adipocyte growth and function and the ACE-processed angiotensin II inhibits adipocyte differentiation. Associations between body mass index (BMI) and ACE polymorphisms have been reported in general populations, but the contribution to severe obesity of this gene, which is located under an obesity genome-scan linkage peak on 17q23, is unknown. ACE is one of the most studied genes and markers responsible for variation in circulating ACE enzyme levels have been extensively characterised. Eight of these variants were genotyped in 1054 severely obese cases and 918 nonobese controls, as well as 116 nuclear families from the genome scan (n=447), enabling the known clades to be inferred. Qualitative analysis of individual single-nucleotide polymorphisms (SNPs), haplotypes, clades, and diploclades demonstrated no significant associations (P<0.05) after minimal correction for multiple testing. Quantitative analysis of clades and diploclades for BMI, waist-to-hip ratio, or ZBMI in children were also not significant. This rigorous, large-scale study of common, well-defined, severe polygenic obesity provides strong evidence that functionally relevant sequence variation in ACE, whether it is defined at the level of SNPs, haplotypes, or clades, is not associated with severe obesity in French Caucasians. Such a study design exemplifies the strategy needed to clearly define the contribution of the ACE gene to the plethora of complex genetic diseases where weak associations have been previously reported.

Case-Control Studies↗

Parental longevity, carotid atherosclerosis, and aortic arterial stiffness in adult offspring.

BACKGROUND AND PURPOSE: We examined the associations of parental longevity with carotid intima-media thickness, carotid plaques, and aortic arterial stiffness in adult offspring. METHODS: A population of 1117 volunteers who participated in the SUVIMAX Vascular Study (mean age, 59.7 years; 49.0% women) were included. Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid B-mode ultrasound examination included measurements (at sites free of plaque) of intima-media thickness at the common carotid arteries and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: The prevalence of carotid plaques in subjects whose fathers had died at <65 years, in those whose fathers were alive at 65 years but who had died by 80 years, and in those whose fathers were alive at 80 years was 40.4%, 30.4%, and 28.9%, respectively (P<0.001). The multivariate odds ratios of carotid plaques in the 3 groups of paternal longevity, adjusted for conventional cardiovascular risk factors, were 1, 0.68 (95% CI, 0.48 to 0.96), and 0.69 (95% CI, 0.49 to 0.98), respectively. The mean common carotid arteries intima-media thickness was higher in subjects with premature paternal death in univariate (P<0.007) but not in multivariate (P=0.39) analyses. Mean PWV decreased with increasing paternal longevity in both univariate and multivariate analyses. The multivariate-adjusted means of PWV in the 3 groups of paternal longevity were 11.9+/-0.14, 11.7+/-0.12, and 11.0+/-0.12 m/s (P<0.0001), respectively. In contrast, neither B-mode ultrasound measurements nor PWV measurements were associated with maternal longevity. CONCLUSIONS: These results may indicate that there are modifications of structure and function of large arteries according to paternal longevity.

Aged↗

Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating.

CONTEXT: Heterozygous mutations in the melanocortin-4 receptor (MC4R) gene are the most common monogenic form of severe obesity in children. There are conflicting reports regarding the prevalence, nature, and pathogenic effects of MC4R mutations in adults with severe late-onset obesity. OBJECTIVE: Our objective was to determine the prevalence of MC4R mutations in a cohort of severely obese adults and to determine the clinical phenotype and the phenotype-genotype relationship within adult MC4R mutation carriers. DESIGN AND SETTING: We conducted an observational study at a referral center. PATIENTS OR OTHER PARTICIPANTS: Participants included 769 adult patients with body mass index of at least 35 kg/m(2) and 444 nonobese control individuals. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: We assessed the prevalence of pathogenic MC4R mutations, functional characteristics of the detected mutations, phenotype, and phenotype-genotype relationship within mutation carriers. RESULTS: The global prevalence of obesity-specific MC4R mutations was 2.6%, and the 95% confidence interval (CI(95)) was 1.5-3.7. The prevalence of MC4R mutations was similar in patients developing obesity in childhood (2.83%; CI(95), 0.9-4.8) and in patients with a later onset of the disease (2.35%; CI(95), 0.9-3.8). Adult obese MC4R mutation carriers did not present with binge eating or with any specific clinical phenotype. The severity of the functional alterations of the mutated MC4Rs and in particular the intracellular retention of the receptor correlates both with the severity and the onset of the obesity in the mutation carriers. CONCLUSIONS: Obese adult carriers of functionally relevant MC4R mutations do not specifically present with binge-eating disorder or a history of early-onset obesity. The onset and severity of the obesity in the carriers is related to the functional severity of the MC4R mutations.

Adult↗

Consumption of antioxidant-rich beverages and risk for breast cancer in French women.

PURPOSE: The objective of the study is to evaluate the relation between antioxidant-rich beverages and the incidence of breast cancer. METHODS: This prospective study consisted of 4396 women without a history of cancer who were participants in the French Supplémentation en Vitamines et Minéraux Antioxydants Study. Beverage consumption was estimated by using three nonconsecutive 24-hour recalls. Incident cancer cases were identified through clinical examinations performed every other year, including, e.g., a screening mammogram, and through a monthly health questionnaire. RESULTS: During the median 6.6 years of follow-up, 95 breast cancers were diagnosed. In a multivariate model, an inverse association between herbal tea consumption and risk for breast cancer was observed (compared with nondrinkers, drinking 1 to 149 mL/d; relative risk [RR], 0.93; 95% confidence interval [CI], 0.48-1.80, and for > or =150 mL/d; RR, 0.43; 95% CI, 0.20-0.94; p for trend = 0.04). Consumption of coffee, tea, fruit juices, or wine was not associated with risk for breast cancer. CONCLUSION: Results of this study suggest that consumption of herbal tea may have a role in the prevention of breast cancer.

Adult↗

Antioxidant vitamins and minerals in prevention of cancers: lessons from the SU.VI.MAX study.

A voluminous body of epidemiological research concerning the potential role of antioxidant nutrients in the prevention of cancers has accumulated over the past few decades. However, results of large recent intervention trials do not support a preventive effect against cancer for supplementation with antioxidant nutrients. Seemingly contradictory results between observational studies and randomised trials can be explained by the fact that doses used in clinical trials were much higher than the highest levels attained by the usual dietary intake which, in observational studies, were found to be associated with the lowest risk of cancer. Recently, the Supplementation en Vitamines et Mine raux Antioxydants (SU.VI.MAX) study, a randomised, double-blind, placebo-controlled primary prevention trial, tested the efficacy of supplementation with a combination of antioxidant vitamins and minerals, at nutritional doses, in reducing the cancer incidence in a general population not selected for risk factors. After 7.5 years, low-dose antioxidant supplementation lowered the total cancer incidence in men only. This may be explained by a lower baseline status of certain antioxidants in men compared to women. Finally, the effect of antioxidant supplementation on the incidence of cancer could depend on baseline antioxidant status (which differs from gender and/or nutritional status) and the health status of subjects (healthy v. cancer high-risk subjects). Antioxidant supplementation may have a beneficial effect upon cancer incidence only in healthy subjects who are not exposed to cancer risk and who have a particularly low baseline status. High doses of antioxidant supplementation may be deleterious in subjects in whom the initial phase of cancer development has already started, and they could be ineffective in well-nourished subjects with adequate antioxidant status.

Antioxidants↗

Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods.

Estimation of dietary intake of polyphenols is difficult, due to limited availability of food composition data and bias inherent to dietary assessment methods. The aim of the present study was to evaluate the associations between the intake of polyphenol-rich foods and the urinary excretion of several phenolic compounds and therefore explore whether these phenolic compounds could be used as a biomarker of intake. Fifty-three participants of the SU.VI.MAX study (a randomised primary-prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases) collected a 24 h urine and a spot urine sample and filled a dietary record during a 2 d period. Thirteen polyphenols and metabolites, chlorogenic acid, caffeic acid, m-coumaric acid, gallic acid, 4-O-methylgallic acid, quercetin, isorhamnetin, kaempferol, hesperetin, naringenin, phloretin, enterolactone and enterodiol, were measured using HPLC-electrospray ionisation-MS-MS. In spot samples apple consumption was positively correlated to phloretin, grapefruit consumption to naringenin, orange to hesperetin, citrus fruit consumption to both naringenin and hesperetin, with r coefficients ranging from 0.31 to 0.57 (P < 0.05). The combination of fruits and/or fruit juices was positively correlated to gallic acid and 4-O-methylgallic acid, isorhamnetin, kaempferol, hesperetin, naringenin and phloretin (r 0.24-0.44, P < 0.05). Coffee consumption was positively correlated to caffeic and chlorogenic acids (r 0.29 and 0.63, P < 0.05 respectively). Black tea and wine consumption were positively correlated with gallic and 4-O-methylgallic acids (r 0.37-0.54, P < 0.001). The present results suggest that several polyphenols measured in a spot urine sample can be used as biomarkers of polyphenol-rich food intake.

4-Butyrolactone↗

Serum ferritin, cardiovascular risk factors and ischaemic heart diseases: a prospective analysis in the SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) cohort.

BACKGROUND: Iron has been suggested to play a role in the development of cardiovascular disease (CVD) through its pro-oxidant properties. However, epidemiological studies on iron status and the risk of CVD have yielded conflicting results. We therefore carried out a prospective study to evaluate the relationship between iron status and CVD in a middle-aged French population. METHODS: In total, 9917 subjects (3223 men aged 45-60 years and 6694 women aged 35-60 years) included in the SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) cohort were followed prospectively for 7.5 years. All cases of ischaemic heart disease (IHD) were identified and validated. CVD risk factors, haemoglobin and serum ferritin concentrations were measured at baseline. FINDINGS: Of men 4.3%, and of women 37.8%, presented at baseline a serum ferritin concentration <30 microg l(-1). During the follow-up, 187 subjects (148 men, 39 women) developed IHD. Serum ferritin was positively associated with total cholesterol, serum triglycerides, systolic and diastolic blood pressure, body mass index and haemoglobin. No linear association was found between serum ferritin and IHD risk in men or in women. CONCLUSION: Our data do not support a major role of iron status in the development of IHD in a healthy general population.

Adult↗

Antioxidant supplementation does not affect fasting plasma glucose in the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France: association with dietary intake and plasma concentrations.

BACKGROUND: Observational data suggest a protective effect of several antioxidants on fasting plasma glucose (FPG) and type 2 diabetes. However, randomized trials have yielded inconsistent results. OBJECTIVES: The first objective was to assess the effect of 7.5 y of antioxidant supplementation on FPG at 7.5 y. The second objective was to examine the epidemiologic association of baseline dietary intakes or plasma antioxidants and FPG (at baseline and at 7.5 y). DESIGN: Subjects (n = 3146) from the Supplementation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) primary prevention trial in France were randomly assigned to receive a daily capsule containing 120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 mug Se, and 20 mg Zn or a placebo. RESULTS: After 7.5 y, no significant difference was observed between age-adjusted mean FPG in men (P = 0.78) and women (P = 0.89) in either group. Baseline beta-carotene dietary intakes and plasma concentrations were inversely associated with FPG in multivariate mixed models (P = 0.0045 and P < 0.0001, respectively). Baseline plasma vitamin C and selenium were negatively (P = 0.0455) and positively (P < 0.0001) associated, respectively, with FPG. CONCLUSIONS: Supplementation with antioxidants at nutritional doses for 7.5 y had no effect on FPG in men or women who followed a balanced diet. An inverse association of baseline beta-carotene dietary intake and plasma concentrations with FPG was found, probably because beta-carotene is an indirect marker of fruit and vegetable intakes.

Antioxidants↗

Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies.

The consumption of fruit and vegetables is associated with a reduced rate of coronary heart disease (CHD) in observational cohorts. The purpose of this study was to assess the strength of this association in a meta-analysis. Cohort studies were selected if they reported relative risks (RRs) and 95% CI for coronary heart disease or mortality and if they presented a quantitative assessment of fruit and vegetable intake. The pooled RRs were calculated for each additional portion of fruit and/or vegetables consumed per day, and the linearity of the associations were examined. Nine studies were eligible for inclusion in the meta-analysis that consisted of 91,379 men, 129,701 women, and 5,007 CHD events. The risk of CHD was decreased by 4% [RR (95% CI): 0.96 (0.93-0.99), P = 0.0027] for each additional portion per day of fruit and vegetable intake and by 7% [0.93 (0.89-0.96), P < 0.0001] for fruit intake. The association between vegetable intake and CHD risk was heterogeneous (P = 0.0043), more marked for cardiovascular mortality [0.74 (0.75-0.84), P < 0.0001] than for fatal and nonfatal myocardial infarction [0.95 (0.92-0.99), P = 0.0058]. Visual inspection of the funnel plot suggested a publication bias, although not statistically significant. Therefore, the reported RRs are probably overestimated. This meta-analysis of cohort studies shows that fruit and vegetable consumption is inversely associated with the risk of CHD. The causal mechanism of this association, however, remains to be demonstrated.

Cohort Studies↗

Genetic analysis of ADIPOR1 and ADIPOR2 candidate polymorphisms for type 2 diabetes in the Caucasian population.

Adiponectin is a metabolic link between adipose tissue and insulin action, mediating part of obesity-associated insulin resistance and type 2 diabetes. Two adiponectin receptors have been identified, and we investigated whether sequence variations in adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) genes could contribute to the genetic risk for type 2 diabetes in a case-control study of 1,498 Caucasian subjects. We sequenced the putative functional regions of the two genes in 48 subjects and selected single nucleotide polymorphisms (SNPs) from the public database. Five SNPs in ADIPOR1 and 12 in ADIPOR2 were tested for association with type 2 diabetes. No SNP of ADIPOR1 showed association in any of the samples from the French population. In contrast, three SNPs of ADIPOR2 showed nominal evidence for association with type 2 diabetes before correction for multiple testing (odds ratio [OR] 1.29-1.37, P = 0.034-0.014); only rs767870, located in intron 6, was replicated in an additional diabetes dataset (n = 636, OR 1.29, P = 0.020) with significant allelic association from the overall meta-analysis of 2,876 subjects (adjusted OR 1.25 [95% CI 1.07-1.45], P = 0.0051). In conclusion, our data suggest a modest contribution of ADIPOR2 variants in diabetes risk in the French population.

Adult↗

Yearly incidence of rhinitis, nasal bleeding, and other nasal symptoms in mature women.

OBJECTIVES/HYPOTHESIS: To evaluate, by a prospective questionnaire study, the incidence of spontaneous nasal pathology in mature women over a 12-month period, in particular nasal bleeding and the relationships of these symptoms with various factors. METHODS: Participants were drawn from a sample of 12,735 adult French volunteers participating in a study of antioxidant nutrients ("SU.VI.MAX"); 3500 women aged 50-64 years were randomly selected from good responders in the SU.Vl.MAX population. The responses of 2197 women were analysed. RESULTS: Nearly 70% of subjects reported at least one episode of rhinitis, with a mean (SD) of 1.88 (2.17) episodes per subject. Rhinitis was related to passive exposure to tobacco smoke (adjusted odds ratio [OR] 1.31, 95% CI 1.05-1.63), menopause (OR 1.47, 95% CI 1.16-1.88), and occupational exposure to vapours or dusts (OR 1.55, 95% CI 1.01-2.37). Nasal bleeding was reported as traces of blood by 16.5% of subjects, and as epistaxis (significant nasal bleeding) by 7.6%. Both symptoms were related to passive exposure to tobacco smoke (OR 1.63, 95% CI 1.22-2.19; OR 1.56, 95% CI 1.05-2.32, respectively) but not to use of systemic or topical medication. CONCLUSION: A substantial number of mature women experience nasal symptoms during the course of a year. Rhinitis and nasal bleeding were correlated with passive exposure to tobacco smoke.

Dust↗

Occurrence of coronary artery disease has an adverse impact on health-related quality of life: a longitudinal controlled study.

BACKGROUND: Longitudinal administration of health-related quality of life instruments to a general, initially healthy population allows for changes to be assessed as they occur, rather than afterwards. The aim here was to investigate the impact of coronary artery disease occurrence on health-related quality of life. RESULTS: The 36-item Short-Form questionnaire was applied to the French SU.VI.MAX cohort in 1996 and 2001. Findings in 62 patients who developed coronary artery disease between the two measures were compared with those in 310 age- and sex-matched cardiovascular-free controls. The mean interval between the initial health-related quality of life assessment and coronary artery disease diagnosis was 34.5 (+/-19.6) months. Between the two health-related quality of life assessments, some dimensions decreased in the coronary artery disease group but not among controls. After adjustment (for body mass index, tobacco habits, diabetes and levels of circulating apolipoprotein A1 and B), the degree of change in health-related quality of life between the two groups differed by: -10.0 points (p=0.02) for the role-physical dimension, -10.6 points (p=0.02) for role-emotional, -4.7 points (p=0.03) for vitality and -8.8 points (p<0.0001) for general health. CONCLUSION: At an average of 2.5 years post-coronary artery disease diagnosis, aspects most likely to be affected were those with a component related to emotional and physical functioning, and vitality and general health. Close examination of the scores for each domain of the SF-36 reveals the most impaired aspects of health-related quality of life in subjects with coronary problems, thereby enabling practitioners to tailor their interventions.

Adult↗

Homocysteine is not associated with arterial thickness and stiffness in healthy middle-aged French volunteers.

BACKGROUND: To study the association between the total plasma homocysteine (tHcy) concentration and the carotid artery intima-medial wall thickness (IMT), pulse wave velocity (PWV) and the presence of arterial plaques in a French population. METHODS: Cross-sectional analysis of data from 556 male and 559 female middle-aged participants (mean (+/-SD) age 59.6+/-4.7 years) provided by an ongoing intervention trial. RESULTS: Mean geometric tHcy concentration was higher for men than for women (10.6 vs. 8.5 micromol/L, p<0.001) and was associated in the expected direction with known determinants. The mean IMT was 0.71+/-0.1 mm for men and 0.69+/-0.1 mm for women (p<0.001), the mean PWV was, respectively, 12.0+/-2.8 and 10.9+/-2.2 m/sec (p<0.001), and the percentages of subjects with plaques were, respectively, 40.8% and 22.7% (p<0.001). In men only, the age-adjusted mean IMT and PWV increased with an increasing tHcy concentration: the IMT was 0.71 mm in the first tHcy-quartile and 0.73 mm in the fourth tHcy-quartile (p for linear trend=0.03), the PWV values were, respectively, 11.6 and 12.4 m/sec (p for linear trend=0.01). These associations disappeared after adjustment for conventional cardiovascular disease risk factors. CONCLUSION: In this population, the tHcy concentration was not associated with measures of arterial thickness and stiffness.

Carotid Artery Diseases↗

Risk of malaria among French adult travellers.

BACKGROUND: Imported malaria remains an important, but often unrecognised, health problem in Europe. Little information exists on the incidence of imported malaria with respect to exposure. This study aimed to estimate the incidence of malaria in a cohort of travellers with respect to protection measures. METHOD: In all 13,017 participants enrolled in a French general population cohort (SU.VI.MAX cohort) and followed-up over 8 years were investigated. All participants received a retrospective questionnaire about travel to malaria-endemic countries relating to countries visited, duration of stay, use of protection measures and chemoprophylaxis. Malaria cases was confirmed from medical records. RESULTS: Data were obtained for 752 individuals who made 1,393 trips to malaria-endemic areas. This sample was predominantly middle-class and high-risk groups such as migrants were not represented. Mechanical protection was used in 589 trips (42.3%) and chemoprophylaxis in 1,017 trips (73.0%). This was appropriate for the zone in 615 trips (44.0%) and adequate compliance was reported in the case of 497 trips (35.6%). Appropriate chemoprophylaxis and physical protection measures were used in 21.7% of the trips. Six laboratory-confirmed cases of imported malaria yielded an estimated incidence density of 148 cases/month of exposure/10,000 travellers. In five cases, appropriate protection measures had not been taken. CONCLUSION: Appropriate chemoprophylaxis and physical protection measures against malaria infection are used by less than one-quarter of a sample of predominantly middle-class travellers from France to endemic areas. More intense education measures need to be implemented to reduce the risk of imported malaria.

Adult↗

Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial.

Randomized trials have shown, unexpectedly, that supplementation with selenium or vitamin E is associated with a reduction of prostate cancer risk. We assess whether a supplementation with low doses of antioxidant vitamins and minerals could reduce the occurrence of prostate cancer and influence biochemical markers. The SU.VI.MAX trial comprised 5,141 men randomized to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years. Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrollment and at the end of follow-up from 3,616 men. Cox regression models were used to estimate the hazard ratio and related 95% confidence interval of prostate cancer associated with the supplementation and to examine whether the effect differed among predetermined susceptible subgroups. During the follow-up, 103 cases of prostate cancer were diagnosed. Overall, there was a moderate nonsignificant reduction in prostate cancer rate associated with the supplementation (hazard ratio = 0.88; 95% CI = 0.60-1.29). However, the effect differed significantly between men with normal baseline PSA (< 3 microg/L) and those with elevated PSA (p = 0.009). Among men with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements (hazard ratio = 0.52; 95% CI = 0.29-0.92). In men with elevated PSA at baseline, the supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (hazard ratio = 1.54; 95% CI = 0.87-2.72). The supplementation had no effect on PSA or IGF levels. Our findings support the hypothesis that chemoprevention of prostate cancer can be achieved with nutritional doses of antioxidant vitamins and minerals.

Adult↗

Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes.

We identified a locus on chromosome 6q16.3-q24.2 (ref. 1) associated with childhood obesity that includes 2.4 Mb common to eight genome scans for type 2 diabetes (T2D) or obesity. Analysis of the gene ENPP1 (also called PC-1), a candidate for insulin resistance, in 6,147 subjects showed association between a three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA; QdelTG) and childhood obesity (odds ratio (OR) = 1.69, P = 0.0006), morbid or moderate obesity in adults (OR = 1.50, P = 0.006 or OR = 1.37, P = 0.02, respectively) and T2D (OR = 1.56, P = 0.00002). The Genotype IBD Sharing Test suggested that this obesity-associated ENPP1 risk haplotype contributes to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver. These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions.

Adult↗