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).

Trajectories of metabolic risk factors and biochemical markers prior to the onset of type 2 diabetes: the population-based longitudinal Doetinchem study.

BACKGROUND: Risk factors often develop at young age and are maintained over time, but it is not fully understood how risk factors develop over time preceding type 2 diabetes. We examined how levels and trajectories of metabolic risk factors and biochemical markers prior to diagnosis differ between persons with and without type 2 diabetes over 15-20 years. METHODS: A total of 355 incident type 2 diabetes cases (285 self-reported, 70 with random glucose ⩾11.1 mmol l-1) and 2130 controls were identified in a prospective cohort between 1987-2012. Risk factors were measured at 5-year intervals. Trajectories preceding case ascertainment were analysed using generalised estimating equations. RESULTS: Among participants with a 21-year follow-up period, those with type 2 diabetes had higher levels of metabolic risk factors and biochemical markers 15-20 years before case ascertainment. Subsequent trajectories were more unfavourable in participants with type 2 diabetes for body mass index (BMI), HDL cholesterol and glucose (P<0.01), and to a lesser extent for waist circumference, diastolic and systolic blood pressure, triglycerides, alanine aminotransferase, gamma glutamyltransferase, C-reactive protein, uric acid and estimated glomerular filtration rate compared with participants without type 2 diabetes. Among persons with type 2 diabetes, BMI increased by 5-8% over 15 years, whereas the increase among persons without type 2 diabetes was 0-2% (P<0.01). The observed differences in trajectories of metabolic risk factors and biochemical markers were largely attenuated after inclusion of BMI in the models. Results were similar for men and women. CONCLUSIONS: Participants with diabetes had more unfavourable levels of metabolic risk factors and biochemical markers already 15-20 years before diagnosis and worse subsequent trajectories than others. Our results highlight the need, in particular, for maintenance of a healthy weight from young adulthood onwards for diabetes prevention.

Alcoholic beverage preference and diabetes incidence across Europe: the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project.

BACKGROUND/OBJECTIVES: It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol. SUBJECTS/METHODS: Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when ⩾70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis. RESULTS: Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases. CONCLUSIONS: This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.

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.

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.

Diabetes in Europe: an update.

Diabetes is among the leading causes of death in the IDF Europe Region (EUR), continues to increase in prevalence with diabetic macro- and microvascular complications resulting in increased disability and enormous healthcare costs. In 2013, the number of people with diabetes is estimated to be 56 million in EUR with an overall estimated prevalence of 8.5%. However, estimates of diabetes prevalence in 2013 vary widely in the 56 diverse countries in EUR from 2.4% in Moldova to 14.9% in Turkey. Trends in diabetes prevalence also vary between countries with stable prevalence since 2002 for many countries but a doubling of diabetes prevalence in Turkey. For 2035, a further increase of nearly 10 million people with diabetes is projected for the EUR. Prevalence of type 1 has also increased over the past 20 years in EUR and there was estimated to be 129,350 cases in children aged 0-14 years in 2013. Registries provide valid information on incidence of type 1 diabetes with more complete data available for children than for adults. There are large differences in distribution of risk factors for diabetes at the population level in EUR. Modifiable risk factors such as obesity, physical inactivity, smoking behaviour (including secondhand smoking), environmental pollutants, psychosocial factors and socioeconomic deprivation could be tackled to reduce the incidence of type 2 diabetes in Europe. In addition, diabetes management is a major challenge to health services in the European countries. Improved networking practices of health professionals and other stakeholders in combination with empowerment of people with diabetes and continuous quality monitoring need to be further developed in Europe.

Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct.

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.

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.

Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis.

Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16,154 participants and 12,403 incident cases of T2D were identified from 340,234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.

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.

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.

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.

Weight change over five-year periods and number of components of the metabolic syndrome in a Dutch cohort.

Overweight and obesity are associated with the metabolic syndrome (MetS). We studied the association of weight change over three consecutive 5-year periods with the number of MetS components in people aged 20-59 years. 5735 participants from the Doetinchem Cohort Study were included. Weight was measured in round 1 and at each 5-year interval follow-up (round 2, 3 and 4). Weight change was defined as the absolute weight change between two consecutive measurements. The number of MetS components (assessed in round 2, 3 and 4) was based on the presence of the following components of the MetS: central obesity, raised blood pressure, reduced high density lipoprotein cholesterol and elevated glucose. Associations of weight change and the number of components of the MetS were analyzed with Generalized Estimating Equations for Poisson regression, stratified for 10-year age groups. For each age group, 1 kg weight gain was positively associated with the number of components of the MetS, independent of sex and measurement round. The association was stronger in 30-39 years (adjusted rate ratio: 1.044; 95%CI: 1.040-1.049) and smaller in older age groups. Compared to stable weight (>-2.5 kg and < 2.5 kg), weight loss (< or = -2.5 kg) and weight gain (> or =2.5 kg) was associated with a lower and higher rate ratio respectively, for the number of components of the MetS. Our results support the independent association of weight change with the number of MetS components with a more pronounced association in younger people.

Does educational level influence lung function decline (Doetinchem Cohort Study)?

Low socioeconomic status is associated with reduced lung function in adults. In addition, there are indications that lung function decline with age is accelerated in low socioeconomic groups, but, to date, findings have been inconclusive. In order to investigate the relation between educational level, forced expiratory volume in 1 s (FEV1) and decline in FEV1 over time, linear mixed-effects models were fitted to baseline and 10-yr-follow-up data from the Doetinchem Cohort Study. The study population (26-66 yrs at baseline) consisted of 2,679 males and 3,026 females with an FEV1 measurement in at least one of the three rounds of follow-up and information on relevant covariables. High educational level was used as the reference class. Low educational level was associated with a higher prevalence of smoking and with a lower smoking-adjusted FEV1 at baseline (-148 mL in males and -47 mL in females). In females, low educational level was associated with a faster FEV1 decline (3.4 mL x yr(-1), age- and height-adjusted), which was not explained by smoking. In males, no differences in rates of decline between educational levels were observed. FEV1 decline was faster in less-educated females, independent of smoking. In males, FEV1 decline did not differ between educational levels.