The Association between BMI and Different Frailty Domains: A U-Shaped Curve?

OBJECTIVES: Previous studies showed a U-shaped association between BMI and (physical) frailty. We studied the association between BMI and physical, cognitive, psychological, and social frailty. Furthermore, the overlap between and prevalence of these frailty domains was examined. DESIGN: Cross-sectional study. SETTING: The Doetinchem Cohort Study is a longitudinal population-based study starting in 1987-1991 examining men and women aged 20-59 with follow-up examinations every 5 yrs. PARTICIPANTS: For the current analyses, we used data from round 5 (2008-2012) with 4019 participants aged 41-81 yrs. MEASUREMENTS: Physical frailty was defined as having ≥ 2 of 4 frailty criteria from the Frailty Phenotype (unintentional weight loss, exhaustion, physical activity, handgrip strength). Cognitive frailty was defined as the < 10th percentile on global cognitive functioning (based on memory, speed, flexibility). Psychological frailty was defined as having 2 out of 2 criteria (depression, mental health). Social frailty was defined as having ≥ 2 of 3 criteria (loneliness, social support, social participation). BMI was divided into four classes. Analyses were adjusted for sex, age, level of education, and smoking. RESULTS: A U-shaped association was observed between BMI and physical frailty, a small linear association for BMI and cognitive frailty and no association between BMI and psychological and social frailty. The four frailty domains showed only a small proportion of overlap. The prevalence of physical, cognitive and social frailty increased with age, whereas psychological frailty did not. CONCLUSION: We confirm that not only underweight but also obesity is associated with physical frailty. Obesity also seems to be associated with cognitive frailty. Further, frailty prevention should focus on multiple domains and target individuals at a younger age (<65yrs).

Dietary intake of carotenoids and risk of type 2 diabetes.

BACKGROUND AND AIMS: Carotenoids may reduce diabetes risk, due to their antioxidant properties. However, the association between dietary carotenoids intake and type 2 diabetes risk is still unclear. Therefore, the objective of this study was to examine whether higher dietary carotenoid intakes associate with reduced type 2 diabetes risk. METHODS AND RESULTS: Data from 37,846 participants of the European Prospective Investigation into Cancer and Nutrition- Netherlands study were analyzed. Dietary intakes of ß-carotene, α-carotene, ß-cryptoxanthin, lycopene, lutein & zeaxanthin and the sum of these carotenoids were assessed using a validated food frequency questionnaire. Incident type 2 diabetes was mainly self-reported, and verified against general practitioner information. Mean ±SD total carotenoid intake was 10 ± 4 mg/day. During a mean ±SD follow-up of 10 ± 2 years, 915 incident cases of type 2 diabetes were ascertained. After adjustment for age, sex, diabetes risk factors, dietary intake, waist circumference and BMI, higher ß-carotene intakes associated inversely with diabetes risk [Hazard Ratio quartile 4 versus quartile 1 (HR(Q4)): 0.78 (95%CI:0.64,0.95), P-linear trend 0.01]. For α-carotene, a borderline significant reduced risk was observed, with a HR(Q4) of 0.85 (95%CI:0.70,1.03), and P-linear trend 0.05. ß-cryptoxanthin, lycopene, lutein & zeaxanthin, and the sum of all carotenoids did not associate with diabetes risk. CONCLUSIONS: This study shows that diets high in ß-carotene and α-carotene are associated with reduced type 2 diabetes in generally healthy men and women.

Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries.

BACKGROUND/OBJECTIVES: Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D. SUBJECTS/METHODS: A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12,403 incident T2D cases and a subcohort of 16,835 people, identified from a cohort of 340,234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis. RESULTS: After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D. CONCLUSIONS: Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.

The validation of cardiovascular risk scores for patients with type 2 diabetes mellitus.

OBJECTIVE: Various cardiovascular prediction models have been developed for patients with type 2 diabetes. Their predictive performance in new patients is mostly not investigated. This study aims to quantify the predictive performance of all cardiovascular prediction models developed specifically for diabetes patients. DESIGN AND METHODS: Follow-up data of 453, 1174 and 584 type 2 diabetes patients without pre-existing cardiovascular disease (CVD) in the EPIC-NL, EPIC-Potsdam and Secondary Manifestations of ARTerial disease cohorts, respectively, were used to validate 10 prediction models to estimate risk of CVD or coronary heart disease (CHD). Discrimination was assessed by the c-statistic for time-to-event data. Calibration was assessed by calibration plots, the Hosmer-Lemeshow goodness-of-fit statistic and expected to observed ratios. RESULTS: There was a large variation in performance of CVD and CHD scores between different cohorts. Discrimination was moderate for all 10 prediction models, with c-statistics ranging from 0.54 (95% CI 0.46 to 0.63) to 0.76 (95% CI 0.67 to 0.84). Calibration of the original models was poor. After simple recalibration to the disease incidence of the target populations, predicted and observed risks were close. Expected to observed ratios of the recalibrated models ranged from 1.06 (95% CI 0.81 to 1.40) to 1.55 (95% CI 0.95 to 2.54), mainly driven by an overestimation of risk in high-risk patients. CONCLUSIONS: All 10 evaluated models had a comparable and moderate discriminative ability. The recalibrated, but not the original, prediction models provided accurate risk estimates. These models can assist clinicians in identifying type 2 diabetes patients who are at low or high risk of developing CVD.

Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study.

BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation. SUBJECTS/METHODS: Using a case-cohort design, 11,245 incident cases of type 2 diabetes and a representative subcohort (N=15,798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N=2347) were used to calibrate habitual intake data derived from dietary questionnaires. RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (Ptrend=0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 µg/day dietary vitamin D. CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study.

AIMS/HYPOTHESIS: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption. RESULTS: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants. CONCLUSIONS/INTERPRETATION: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.

The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: the EPIC-InterAct study.

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.

Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size The EPIC-InterAct study.

OBJECTIVE: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. DESIGN: Multicentre prospective case-cohort study. SETTING: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. SUBJECTS: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. INTERVENTIONS: Alcohol consumption assessed using validated dietary questionnaires. MAIN OUTCOME MEASURES: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. RESULTS: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.78-1.05) for 6.1-12.0 versus 0.1-6.0 g day(-1) , adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.1-96.0 g day(-1) with an HR of 0.86 (95% CI: 0.75-0.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.72-0.92) for 6.1-12.0 g day(-1) (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI ≥ 25 kg m(-2) ) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.79-1.03 for 6.1-12.0 g day(-1) ). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. CONCLUSIONS: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.

Serum micronutrient concentrations and childhood asthma: the PIAMA birth cohort study.

BACKGROUND: Research suggests an influence of micronutrients on childhood asthma. So far, evidence mainly originates from cross-sectional studies using nutrient intake data, which is not an accurate measure of nutrient status. This study aimed to investigate the cross-sectional and prospective associations between serum concentrations of magnesium, vitamin D, selenium, and zinc and prevalence of (severe) asthma, atopy, and bronchial hyperresponsiveness (BHR) in childhood. METHODS: In the Prevention and Incidence of Asthma and Mite Allergy birth cohort study, serum nutrient concentrations were available for a 4-yr-old subgroup (n = 372) and for a different 8-yr-old subgroup (n = 328). Yearly questionnaires inquired about asthma prevalence until 8 yr of age. Allergic sensitization was measured at 4 and 8 yr of age; BHR was measured at 8 yr of age. Data were analyzed with logistic regression and generalized estimating equations models. RESULTS: There was a consistent (non-significant) inverse association between serum magnesium concentrations and asthma prevalence. Serum vitamin D concentrations measured at age 4 were inversely associated with asthma at ages 4-8 [e.g., cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma: odds ratio (OR): 0.49, 95% confidence interval (CI): 0.25-0.95], whereas vitamin D measured at age 8 was positively associated with asthma at age 8 (e.g., cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma: OR: 2.14, 95% CI: 0.67-6.82). CONCLUSIONS: Our study contributes to the evidence that children with higher serum magnesium concentrations are less likely to have asthma. The associations between serum vitamin D concentrations and asthma were age-dependent.

Mediterranean diet and type 2 diabetes risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study: the InterAct project.

OBJECTIVE: To study the association between adherence to the Mediterranean dietary pattern (MDP) and risk of developing type 2 diabetes, across European countries. RESEARCH DESIGN AND METHODS: We established a case-cohort study including 11,994 incident type 2 diabetic case subjects and a stratified subcohort of 15,798 participants selected from a total cohort of 340,234 participants with 3.99 million person-years of follow-up, from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The relative Mediterranean diet score (rMED) (score range 0-18) was used to assess adherence to MDP on the basis of reported consumption of nine dietary components characteristic of the Mediterranean diet. Cox proportional hazards regression, modified for the case-cohort design, was used to estimate the association between rMED and risk of type 2 diabetes, adjusting for confounders. RESULTS: The multiple adjusted hazard ratios of type 2 diabetes among individuals with medium (rMED 7-10 points) and high adherence to MDP (rMED 11-18 points) were 0.93 (95% CI 0.86-1.01) and 0.88 (0.79-0.97), respectively, compared with individuals with low adherence to MDP (0-6 points) (P for trend 0.013). The association between rMED and type 2 diabetes was attenuated in people <50 years of age, in obese participants, and when the alcohol, meat, and olive oil components were excluded from the score. CONCLUSIONS: In this large prospective study, adherence to the MDP, as defined by rMED, was associated with a small reduction in the risk of developing type 2 diabetes in this European population.

Food intake of individuals with and without diabetes across different countries and ethnic groups.

BACKGROUND/OBJECTIVES: Given the importance of nutrition therapy in diabetes management, we hypothesized that food intake differs between individuals with and without diabetes. We investigated this hypothesis in two large prospective studies including different countries and ethnic groups. SUBJECTS/METHODS: Study populations were the European Prospective Investigation into Cancer and Nutrition Study (EPIC) and the Multiethnic Cohort Study (MEC). Dietary intake was assessed by food frequency questionnaires, and calibrated using 24h-recall information for the EPIC Study. Only confirmed self-reports of diabetes at cohort entry were included: 6192 diabetes patients in EPIC and 13 776 in the MEC. For the cross-sectional comparison of food intake and lifestyle variables at baseline, individuals with and without diabetes were matched 1:1 on sex, age in 5-year categories, body mass index in 2.5 kg/m(2) categories and country. RESULTS: Higher intake of soft drinks (by 13 and 44% in the EPIC and MEC), and lower consumption of sweets, juice, wine and beer (>10% difference) were observed in participants with diabetes compared with those without. Consumption of vegetables, fish and meat was slightly higher in individuals with diabetes in both studies, but the differences were <10%. Findings were more consistent across different ethnic groups than countries, but generally showed largely similar patterns. CONCLUSIONS: Although diabetes patients are expected to undergo nutritional education, we found only small differences in dietary behavior in comparison with cohort members without diabetes. These findings suggest that emphasis on education is needed to improve the current behaviors to assist in the prevention of complications.

Maternal and paternal transmission of type 2 diabetes: influence of diet, lifestyle and adiposity.

OBJECTIVE: Transmission of family history of type 2 diabetes to the next generation is stronger for maternal than paternal diabetes in some populations. The aim of the present study was to investigate whether this difference is explained by diet, lifestyle factors and/or adiposity. METHODS: We analysed 35174 participants from the Dutch contribution to the European Prospective Investigation into Cancer and Nutrition, a prospective population-based cohort (aged 20-70 years) with a median follow-up of 10.2 years. Parental history of diabetes was self-reported. Occurrence of diabetes was mainly identified by self-report and verified by medical records. RESULTS: Amongst 35174 participants, 799 incident cases of diabetes were observed. In age- and sex-adjusted analyses, hazard ratio (HR) and 95% confidence intervals (CIs) for diabetes by maternal and paternal diabetes were 2.66 (2.26-3.14) and 2.40 (1.91-3.02), respectively. Maternal transmission of risk of diabetes was explained by diet (9.4%), lifestyle factors including smoking, alcohol consumption, physical activity and educational level (7.8%) and by adiposity, i.e. body mass index and waist and hip circumference (23.5%). For paternal transmission, the corresponding values were 2.9%, 0.0% and 9.6%. After adjustment for diet, lifestyle factors and adiposity, the HRs for maternal (2.20; 95% CI, 1.87-2.60) and paternal (2.23; 95% CI, 1.77-2.80) transmission of diabetes were comparable. CONCLUSIONS: Both maternal and paternal diabetes are associated with increased risk of type 2 diabetes, independently of diet, lifestyle and adiposity. The slightly higher risk conferred by maternal compared to paternal diabetes was explained by a larger contribution of diet, lifestyle factors and adiposity.

Non-fasting lipids and risk of cardiovascular disease in patients with diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to examine the effect of postprandial time on the associations and predictive value of non-fasting lipid levels and cardiovascular disease risk in participants with diabetes. METHODS: This study was conducted among 1,337 participants with diabetes from the Dutch and German (Potsdam) contributions to the European Prospective Investigation into Cancer and Nutrition. At baseline, total cholesterol, LDL- and HDL-cholesterol and triacylglycerol concentrations were measured and the ratio of total cholesterol/HDL-cholesterol was calculated. Participants were followed for incidence of cardiovascular disease. RESULTS: Lipid concentrations changed minimally with increasing postprandial time, except for triacylglycerol which was elevated just after a meal and declined over time (1.86 at 0.1 h to 1.33 at >6 h, p for trend <0.001). During a mean follow-up of 8 years, 116 cardiovascular events were documented. After adjustment for potential confounders, triacylglycerol (HR for third tertile compared with first tertile (HR(t)3(to)1), 1.73 [95% CI 1.04, 2.87]), HDL-cholesterol (HR(t)3(to)1, 0.41 [95% CI 0.23, 0.72]) and total cholesterol/HDL-cholesterol ratio (HR(t)3(to)1, 1.65 [95% CI 0.95, 2.85]) were associated with cardiovascular disease, independent of postprandial time. Cardiovascular disease risk prediction using the UK Prospective Diabetes Study risk engine was not affected by postprandial time. CONCLUSIONS/INTERPRETATION: Postprandial time did not affect associations between lipid concentrations and cardiovascular disease risk in patients with diabetes, nor did it influence prediction of cardiovascular disease. Therefore, it may not be necessary to use fasting blood samples to determine lipid concentrations for cardiovascular disease risk prediction in patients with diabetes.

Intake of total, animal and plant protein and subsequent changes in weight or waist circumference in European men and women: the Diogenes project.

BACKGROUND: As protein is considered to increase thermogenesis and satiety more than other macronutrients, it may have beneficial effects on prevention of weight gain and weight maintenance. OBJECTIVE: The objective of this study is to assess the association between the amount and type of dietary protein, and subsequent changes in weight and waist circumference (WC). METHODS: 89,432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a mean of 6.5 years. Associations between the intake of protein or subgroups of protein (from animal and plant sources) and changes in weight (g per year) or WC (cm per year) were investigated using gender and centre-specific multiple regression analyses. Adjustments were made for other baseline dietary factors, baseline anthropometrics, demographic and lifestyle factors and follow-up time. We used random effect meta-analyses to obtain pooled estimates across centres. RESULTS: Higher intake of total protein, and protein from animal sources was associated with subsequent weight gain for both genders, strongest among women, and the association was mainly attributable to protein from red and processed meat and poultry rather than from fish and dairy sources. There was no overall association between intake of plant protein and subsequent changes in weight. No clear overall associations between intakes of total protein or any of the subgroups and changes in WC were present. The associations showed some heterogeneity between centres, but pooling of estimates was still considered justified. CONCLUSION: A high intake of protein was not found associated with lower weight or waist gain in this observational study. In contrast, protein from food items of animal origin, especially meat and poultry, seemed to be positively associated with long-term weight gain. There were no clear associations for waist changes.

External validation of the UK Prospective Diabetes Study (UKPDS) risk engine in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Treatment guidelines recommend the UK Prospective Diabetes Study (UKPDS) risk engine for predicting cardiovascular risk in patients with type 2 diabetes, although validation studies showed moderate performance. The methods used in these validation studies were diverse, however, and sometimes insufficient. Hence, we assessed the discrimination and calibration of the UKPDS risk engine to predict 4, 5, 6 and 8 year cardiovascular risk in patients with type 2 diabetes. METHODS: The cohort included 1,622 patients with type 2 diabetes. During a mean follow-up of 8 years, patients were followed for incidence of CHD and cardiovascular disease (CVD). Discrimination and calibration were assessed for 4, 5, 6 and 8 year risk. Discrimination was examined using the c-statistic and calibration by visually inspecting calibration plots and calculating the Hosmer-Lemeshow χ(2) statistic. RESULTS: The UKPDS risk engine showed moderate to poor discrimination for both CHD and CVD (c-statistic of 0.66 for both 5 year CHD and CVD risks), and an overestimation of the risk (224% and 112%). The calibration of the UKPDS risk engine was slightly better for patients with type 2 diabetes who had been diagnosed with diabetes more than 10 years ago compared with patients diagnosed more recently, particularly for 4 and 5 year predicted CVD and CHD risks. Discrimination for these periods was still moderate to poor. CONCLUSIONS/INTERPRETATION: We observed that the UKPDS risk engine overestimates CHD and CVD risk. The discriminative ability of this model is moderate, irrespective of various subgroup analyses. To enhance the prediction of CVD in patients with type 2 diabetes, this model should be updated.

Ascertainment and verification of diabetes in the EPIC-NL study.

BACKGROUND: The objectives of this study were to describe in detail the ascertainment and verification of prevalent and incident diabetes in the Dutch contributor to the European Prospective Investigation into Cancer and Nutrition (EPIC-NL cohort) and to examine to what extent ascertained diabetes agreed with general practitioner (GP) and pharmacy records. METHODS: In total, 40,011 adults, aged 21 to 70 years at baseline, were included. Diabetes was ascertained via self-report, linkage to registers of hospital discharge diagnoses (HDD) and a urinary glucose strip test. Ascertained diabetes cases were verified against GP or pharmacist information using mailed questionnaires. RESULTS: At baseline, 795 (2.0%) diabetes cases were ascertained, and 1494 (3.7%) during a mean follow-up of ten years. The majority was ascertained via self-report only (56.7%), or self-report in combination with HDD (18.0%). After verification of ascertained diabetes cases, 1532 (66.9%) [corrected] were defined as having diabetes , 495 (21.6%) as non-diabetic individuals, and 262 (11.5%) as uncertain. Of the 1538 cases ascertained by self-report, 1350 (positive predictive value: 87.8%) were confirmed by GP or pharmacist. Cases ascertained via self-report in combination with HDD were most often confirmed (334 (positive predictive value: 96.0%)). CONCLUSIONS: Two out of three ascertained diabetes cases were confirmed to have been diagnosed with diabetes by their GP or pharmacist. Diabetes cases ascertained via self-report in combination with HDD had the highest confirmation.

Dietary glycaemic index and glycaemic load in the European Prospective Investigation into Cancer and Nutrition.

OBJECTIVES: To describe dietary glycaemic index (GI) and glycaemic load (GL) values in the population participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study according to food groups, nutrients and lifestyle characteristics. METHODS: Single 24-h dietary recalls (24-HDRs) from 33 566 subjects were used to calculate dietary GI and GL, and an ad hoc database was created as the main reference source. Mean GI and GL intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. RESULTS: GI was the lowest in Spain and Germany, and highest in the Netherlands, United Kingdom and Denmark for both genders. In men, GL was the lowest in Spain and Germany and highest in Italy, whereas in women, it was the lowest in Spain and Greece and highest in the UK health-conscious cohort. Bread was the largest contributor to GL in all centres (15-45%), but it also showed the largest inter-individual variation. GL, but not GI, tended to be lower in the highest body mass index category in both genders. GI was positively correlated with starch and intakes of bread and potatoes, whereas it was correlated negatively with intakes of sugar, fruit and dairy products. GL was positively correlated with all carbohydrate components and intakes of cereals, whereas it was negatively correlated with fat and alcohol and with intakes of wine, with large variations across countries. CONCLUSIONS: GI means varied modestly across countries and genders, whereas GL means varied more, but it may possibly act as a surrogate of carbohydrate intake.

Coffee and tea consumption and risk of type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the association of consumption of coffee and tea, separately and in total, with risk of type 2 diabetes and which factors mediate these relations. METHODS: This research was conducted as part of the Dutch Contribution to the European Prospective Investigation into Cancer and Nutrition, which involves a prospective cohort of 40,011 participants with a mean follow-up of 10 years. A validated food-frequency questionnaire was used to assess coffee and tea consumption and other lifestyle and dietary factors. The main outcome was verified incidence of type 2 diabetes. Blood pressure, caffeine, magnesium and potassium were examined as possible mediating factors. RESULTS: During follow-up, 918 incident cases of type 2 diabetes were documented. After adjustment for potential confounders, coffee and tea consumption were both inversely associated with type 2 diabetes, with hazard ratios of 0.77 (95% CI 0.63-0.95) for 4.1-6.0 cups of coffee per day (p for trend = 0.033) and 0.63 (95% CI: 0.47-0.86) for >5.0 cups of tea per day (p for trend = 0.002). Total daily consumption of at least three cups of coffee and/or tea reduced the risk of type 2 diabetes by approximately 42%. Adjusting for blood pressure, magnesium, potassium and caffeine did not attenuate the associations. CONCLUSIONS/INTERPRETATION: Drinking coffee or tea is associated with a lowered risk of type 2 diabetes, which cannot be explained by magnesium, potassium, caffeine or blood pressure effects. Total consumption of at least three cups of coffee or tea per day may lower the risk of type 2 diabetes.

Dietary glycaemic index, glycaemic load and subsequent changes of weight and waist circumference in European men and women.

OBJECTIVES: To investigate whether dietary glycaemic index (GI) and glycaemic load (GL) were associated with subsequent weight and waist circumference change. DESIGN: Population-based prospective cohort study. SETTING: Five European countries, which are Denmark, Germany, Italy, The Netherlands and the United Kingdom. PARTICIPANTS: A total of 89,432 participants, aged 20-78 years (mean =53 years) at baseline and followed for 1.9-12.5 years (mean=6.5 years). All participants were free of self-reported cancer, cardiovascular diseases and diabetes at baseline. METHODS: Glycaemic index and GL were calculated on the basis of dietary intake assessed by food frequency questionnaires and by using a GI table developed for this study with published GI values as the main sources. Anthropometric data were collected both at baseline and at the end of follow-up. Multiple linear regression analyses were conducted in each centre and random-effect meta-analyses were used to combine the effects. Adjustment was made for baseline anthropometrics, demographic and lifestyle factors, follow-up duration and other dietary factors. RESULTS: Mean GI and GL were 57 and 134, respectively. Associations of GI and GL with subsequent changes of weight and waist circumference were heterogeneous across centres. Overall, with every 10-unit higher in GI, weight increased by 34 g per year (95% confidence interval (CI): -47, 115) and waist circumference increased by 0.19 cm per year (95% CI: 0.11, 0.27). With every 50-unit higher in GL, weight increased by 10 g per year (95% CI: -65, 85) and waist circumference increased by 0.06 cm per year (95% CI: -0.01, 0.13). CONCLUSIONS: Our findings do not support an effect of GI or GL on weight change. The positively significant association between GI, not GL, and subsequent gain in waist circumference may imply a beneficial role of lower GI diets in the prevention of abdominal obesity. However, further studies are needed to confirm this finding given the small effect observed in this study.

Genetic variations in regulatory pathways of fatty acid and glucose metabolism are associated with obesity phenotypes: a population-based cohort study.

BACKGROUND: As nuclear receptors and transcription factors have an important regulatory function in adipocyte differentiation and fat storage, genetic variation in these key regulators and downstream pathways may be involved in the onset of obesity. OBJECTIVE: To explore associations between single nucleotide polymorphisms (SNPs) in candidate genes from regulatory pathways that control fatty acid and glucose metabolism, and repeated measurements of body mass index (BMI) and waist circumference in a large Dutch study population. METHODS: Data of 327 SNPs across 239 genes were analyzed for 3575 participants of the Doetinchem cohort, who were examined three times during 11 years, using the Illumina Golden Gate assay. Adjusted random coefficient models were used to analyze the relationship between SNPS and obesity phenotypes. False discovery rate q-values were calculated to account for multiple testing. Significance of the associations was defined as a q-value < or = 0.20. RESULTS: Two SNPs (in NR1H4 and SMARCA2 in women only) were significantly associated with both BMI and waist circumference. In addition, two SNPs (in SIRT1 and SCAP in women only) were associated with BMI alone. A functional SNP, in IL6, was strongly associated with waist. CONCLUSION: In this explorative study among participants of a large population-based cohort, five SNPs, mainly located in transcription mediator genes, were strongly associated with obesity phenotypes. The results from whole genome and candidate gene studies support the potential role of NR1H4, SIRT1, SMARCA2 and IL6 in obesity. Although replication of our findings and further research on the functionality of these SNPs and underlying mechanism is necessary, our data indirectly suggest a role of GATA transcription factors in weight control.