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Objective: We evaluated the relationship between hip and waist circumferences (HCs, WCs), waist-to-hip ratio, height, weight and body mass index (BMI) and breast cancer risk according to menopausal status of women and cancer hormone receptor status. Design: We used data from the French E3N longitudinal prospective cohort. Subjects: In the total population of 63 726 women who were analyzed, 1887 breast cancer cases were diagnosed during follow-up. Results: Among postmenopausal women, the risk of ER+/PR+ breast cancer increased with increasing weight, BMI, and both HCs and WCs, although these two associations disappeared after adjustment for BMI. No association was seen with ER−/PR− breast cancers. Among premenopausal women, among the different factors studied, HC only (no association was observed for any of the different factors studied except for HC) was associated with an increased risk of ER+/PR+ breast cancer after adjustment for BMI (hazard ratio (HR)=1.65; (1.04–2.62) when comparing the highest to lowest tertile; P -trend across tertiles=0.03) and of ER−/PR− breast cancer both before and after adjustment for BMI (HR=2.85 (1.33–6.13); P -trend <0.01, and HR=3.13 (1.19–8.27) P -trend =0.02, respectively). In the latter group, the association with HC was observed whatever the WC (HR=2.81 (1.18–6.70) and HR=2.79 (1.16–6.76) in women with high HC/low WC and high HC/high WC, respectively). Conclusion: The increase in risk of premenopausal breast cancer associated with large HC for both ER+/PR+ and ER−/PR− subtypes may provide insight into a specific risk factor for premenopausal breast cancer.

Aims/hypothesis We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. Methods The InterAct case–cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. Results A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Conclusions/interpretation Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.

Objective: We evaluated the relationship between hip and waist circumferences (HCs, WCs), waist-to-hip ratio, height, weight and body mass index (BMI) and breast cancer risk according to menopausal status of women and cancer hormone receptor status. Design: We used data from the French E3N longitudinal prospective cohort. Subjects: In the total population of 63 726 women who were analyzed, 1887 breast cancer cases were diagnosed during follow-up. Results: Among postmenopausal women, the risk of ER + /PR + breast cancer increased with increasing weight, BMI, and both HCs and WCs, although these two associations disappeared after adjustment for BMI. No association was seen with ER-/PR- breast cancers. Among premenopausal women, among the different factors studied, HC only (no association was observed for any of the different factors studied except for HC) was associated with an increased risk of ER + /PR + breast cancer after adjustment for BMI (hazard ratio (HR) = 1.65;(1.04-2.62) when comparing the highest to lowest tertile; P-trend across tertiles = 0.03) and of ER-/PR- breast cancer both before and after adjustment for BMI (HR = 2.85 (1.33-6.13);P-trend < 0.01, and HR = 3.13 (1.19-8.27) P-trend = 0.02, respectively). In the latter group, the association with HC was observed whatever the WC (HR = 2.81 (1.18-6.70) and HR = 2.79 (1.16-6.76) in women with high HC/low WC and high HC/high WC, respectively). Conclusion: The increase in risk of premenopausal breast cancer associated with large HC for both ER + /PR + and ER-/PR- subtypes may provide insight into a specific risk factor for premenopausal breast cancer. International Journal of Obesity (2012) 36, 431-439; doi: 10.1038/ijo.2011.66; published online 22 March 2011 Keywords: breast cancer; hip circumference; waist circumference; body mass index; hormone receptor; anthropometric measurements

Aims/hypothesis Islet autoimmunity may progress to adult-onset diabetes. We investigated whether circulating odd-chain fatty acids (OCFA) 15:0 and 17:0, which are inversely associated with type 2 diabetes, interact with autoantibodies against GAD65 (GAD65Ab) on the incidence of adult-onset diabetes. Methods We used the European EPIC-InterAct case–cohort study including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals. Adjusted Prentice-weighted Cox regression estimated HRs and 95% CIs of diabetes in relation to 1 SD lower plasma phospholipid 15:0 and/or 17:0 concentrations or their main contributor, dairy intake, among GAD65Ab-negative and -positive individuals. Interactions between tertiles of OCFA and GAD65Ab status were estimated by proportion attributable to interaction (AP). Results Low concentrations of OCFA, particularly 17:0, were associated with a higher incidence of adult-onset diabetes in both GAD65Ab-negative (HR 1.55 [95% CI 1.48, 1.64]) and GAD65Ab-positive (HR 1.69 [95% CI 1.34, 2.13]) individuals. The combination of low 17:0 and high GAD65Ab positivity vs high 17:0 and GAD65Ab negativity conferred an HR of 7.51 (95% CI 4.83, 11.69), with evidence of additive interaction (AP 0.25 [95% CI 0.05, 0.45]). Low dairy intake was not associated with diabetes incidence in either GAD65Ab-negative (HR 0.98 [95% CI 0.94, 1.02]) or GAD65Ab-positive individuals (HR 0.97 [95% CI 0.79, 1.18]). Conclusions/interpretation Low plasma phospholipid 17:0 concentrations may promote the progression from GAD65Ab positivity to adult-onset diabetes. Graphical Abstract

Aims/hypothesis Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. Methods We established a case–cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case–cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. Results In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. Conclusions/interpretation This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.

Aims/hypothesis Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association. Methods A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created. Results A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history. Conclusions/interpretation Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.

Introduction An increasing number of individuals continue reporting symptoms following the acute stage of Covid-19 infection. Few studies have investigated the factors related to Long Covid. Our aim was to assess how multimorbidity, socio-economic factors (immigration, education, employment, and income), and country of residence affect the presence and number of persistent symptoms attributable to Covid-19 illness in Europe. Methods We used data from the SHARE Corona surveys collected in 2020 and 2021. The sample included 4,004 respondents aged 50 years and older who were affected by the Corona virus. The outcome was the number of persistent symptoms attributable to Covid-19 illness, including: fatigue; cough, congestion, shortness of breath; loss of taste or smell; headache; body aches, joint pain; chest or abdominal pain; diarrhoea, nausea; and confusion. We conducted a multilevel analysis for a hurdle model with negative binomial distribution. Results Overall, 73% of respondents were estimated to have at least one persistent symptom associated with Covid-19 illness and, on average, they had 2.73 symptoms. However, there were some statistically significant across country differences in the presence and number of symptoms. Respondents who were employed were more likely to report at least one symptom (OR = 1.40) and those with higher levels of education were less likely to report any symptoms (OR = 0.67). Respondents with multimorbidity had an increased risk of experiencing an additional symptom (RR = 1.12) while respondents who were employed had a decreased risk of experiencing an additional symptom (RR = 0.85). Discussion and conclusions Presence and number of persistent symptoms associated with Covid-19 illness was highly prevalent and varied significantly across European countries. Evidence from the present work underscores the need to target high-risk groups and those with multimorbidity to reduce long-term health consequences of Covid-19.

Purpose Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. Methods A total of 255,170 participants aged 25–70 years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured N ε -(carboxymethyl)-lysine (CML), N ε -(1-carboxyethyl)-lysine (CEL), and N δ -(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. Results A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087–0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041–0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. Conclusion In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Dietary questionnaires currently available which can assess the habitual diet are timely, costly, or not adapted well to the modern diet; thus, there is a need for a shorter food frequency e-Questionnaire (FFeQ) adapted to Western diets, in order to properly estimate energy and macronutrient intakes or rank individuals according to food and nutrient intakes. The aim of this study was to evaluate the relative validity and reproducibility of a 30-minute and 44-item FFeQ in a sample of adults obtained from the general population. A sample of French adults was recruited through social media and an advertising campaign. A total of 223 volunteers completed the FFeQ twice at one-year intervals and were included in the reproducibility study. During that interval, 92 participants completed three-to-six 24-hour recalls and were included in the validity study. Nutrient and dietary intakes were computed for all validity and reproducibility participants. The level of agreement between the two methods was evaluated for nutrient and food group intakes using classification into quintiles of daily intake, correlation coefficients and Bland-Altman plots. For relative validity, correlation coefficients ranged from 0.09 to 0.88 (unadjusted correlation coefficients, median: 0.48) and 0.02 to 0.68 (deattenuated and energy adjusted correlation coefficients, median: 0.50) for food group and nutrient intakes, respectively. The median proportion of subjects classified into the same or adjacent quintile was 73% and 66% for food and nutrient intakes, respectively. Bland-Altman plots showed good agreement across the range of intakes. Regarding reproducibility, intraclass correlation coefficients ranged from 0.33 to 0.72 (median: 0.60) and 0.55 to 0.73 (median: 0.64), for food and nutrient intakes, respectively. The FFeQ showed acceptable validity and reproducibility in a sample of adults based on their food and nutrient intakes. The FFeQ is a promising and low-cost tool that can be used in large-scale online epidemiological studies or clinical routines and could be integrated into evidence-based smartphone apps for assessing diet components.

Heath, A.K., Muller, D.C., Van Den Brandt, P.A., Papadimitriou, N., Critselis, E., Gunter, M., Vineis, P., Weiderpass, E., Fagherazzi, G., Boeing, H., Ferrari, P., Olsen, A., Tjønneland, A., Arveux, P., Boutron-Ruault, M.-C., Mancini, F.R., Kühn, T., Turzanski-Fortner, R., Schulze, M.B., Karakatsani, A., Thriskos, P., Trichopoulou, A., Masala, G., Contiero, P., Ricceri, F., Panico, S., Bueno-De-Mesquita, B., Bakker, M.F., Van Gils, C.H., Olsen, K.S., Skeie, G., Lasheras, C., Agudo, A., Rodríguez-Barranco, M., Sánchez, M.-J., Amiano, P., Chirlaque, M.-D., Barricarte, A., Drake, I., Ericson, U., Johansson, I., Winkvist, A., Key, T., Freisling, H., His, M., Huybrechts, I., Christakoudi, S., Ellingjord-Dale, M., Riboli, E., Tsilidis, K.K., Tzoulaki, I.