Ivonne Sluijs

Dietary Intake of Total, Animal, and Vegetable Protein and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL Study

OBJECTIVE Dietary recommendations are focused mainly on relative dietary fat and carbohydrate content in relation to diabetes risk. Meanwhile, high-protein diets may contribute to disturbance of glucose metabolism, but evidence from prospective studies is scarce. We examined the association among dietary total, vegetable, and animal protein intake and diabetes incidence and whether consuming 5 energy % from protein at the expense of 5 energy % from either carbohydrates or fat was associated with diabetes risk. RESEARCH DESIGN AND METHODS A prospective cohort study was conducted among 38,094 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Dietary protein intake was measured with a validated food frequency questionnaire. Incident diabetes was verified against medical records. RESULTS During 10 years of follow-up, 918 incident cases of diabetes were documented. Diabetes risk increased with higher total protein (hazard ratio 2.15 [95% CI 1.77–2.60] highest vs. lowest quartile) and animal protein (2.18 [1.80–2.63]) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk. CONCLUSIONS Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful.

A high menaquinone intake reduces the incidence of coronary heart disease

BACKGROUND AND AIM Vitamin K dependent proteins have been demonstrated to inhibit vascular calcification. Data on the effect of vitamin K intake on coronary heart disease (CHD) risk, however, are scarce. To examine the relationship between dietary vitamins K(1) and K(2) intake, and its subtypes, and the incidence of CHD. METHODS AND RESULTS We used data from the Prospect-EPIC cohort consisting of 16,057 women, enrolled between 1993 and 1997 and aged 49-70 years, who were free of cardiovascular diseases at baseline. Intake of vitamin K and other nutrients was estimated with a food frequency questionnaire. Multivariate Cox proportional hazards models were used to analyse the data. After a mean+/-SD follow-up of 8.1+/-1.6 years, we identified 480 incident cases of CHD. Mean vitamin K(1) intake was 211.7+/-100.3 microg/d and vitamin K(2) intake was 29.1+/-12.8 microg/d. After adjustment for traditional risk factors and dietary factors, we observed an inverse association between vitamin K(2) and risk of CHD with a Hazard Ratio (HR) of 0.91 [95% CI 0.85-1.00] per 10 microg/d vitamin K(2) intake. This association was mainly due to vitamin K(2) subtypes MK-7, MK-8 and MK-9. Vitamin K(1) intake was not significantly related to CHD. CONCLUSIONS A high intake of menoquinones, especially MK-7, MK-8 and MK-9, could protect against CHD. However, more research is necessary to define optimal intake levels of vitamin K intake for the prevention of CHD.

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.

Carbohydrate quantity and quality and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition–Netherlands (EPIC-NL) study

BACKGROUND Carbohydrate quantity and quality may play an important role in the development of type 2 diabetes. OBJECTIVE We investigated the associations of dietary glycemic load (GL), glycemic index (GI), carbohydrate, and fiber intake with the incidence of type 2 diabetes. DESIGN A prospective cohort study was conducted in 37,846 participants of the EPIC-NL (European Prospective Investigation into Cancer and Nutrition-Netherlands) study, aged 21-70 y at baseline and free of diabetes. Dietary intake was assessed with the use of a validated food-frequency questionnaire. Incident diabetes cases were mainly self-reported and verified against general practitioner records. RESULTS During a mean follow-up of 10 y, 915 incident diabetes cases were documented. Dietary GL was associated with an increased diabetes risk after adjustment for age, sex, established diabetes risk factors, and dietary factors [hazard ratio (HR) per SD increase: 1.27; 95% CI: 1.11, 1.44; P < 0.001] [corrected]. GI tended to increase diabetes risk (HR: 1.08; 95% CI: 1.00, 1.17; P = 0.05). Dietary fiber was inversely associated with diabetes risk (HR: 0.92; 95% CI: 0.85, 0.99; P < 0.05), whereas carbohydrate intake was associated with increased diabetes risk (HR: 1.15; 95% CI: 1.01, 1.32; P < 0.05). Of the carbohydrate subtypes, only starch was related to increased diabetes risk [HR: 1.25 (1.07, 1.46), P < 0.05]. All associations became slightly stronger after exclusion of energy misreporters. CONCLUSIONS Diets high in GL, GI, and starch and low in fiber were associated with an increased diabetes risk. Both carbohydrate quantity and quality seem to be important factors in diabetes prevention. Energy misreporting contributed to a slight attenuation of associations.

Fruit and Vegetable Consumption and Mortality European Prospective Investigation Into Cancer and Nutrition

In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.

Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-InterAct case-cohort study.

A collaborative re-analysis of data from the InterAct case-control study conducted by Claudia Langenberg and colleagues has established that waist circumference is associated with risk of type 2 diabetes, independently of body mass index.

Dietary Carotenoid Intake Is Associated with Lower Prevalence of Metabolic Syndrome in Middle-Aged and Elderly Men

Carotenoids have antioxidant properties. Little is known about the relation of dietary carotenoid intake on metabolic syndrome risk. We examined whether dietary carotenoid intake was associated with metabolic syndrome and metabolic syndrome risk factors. We conducted a population-based, cross-sectional study in 374 men aged 40-80 y. Intakes of beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin were estimated using a validated FFQ. Presence of metabolic syndrome was determined using fasting serum glucose, triglyceride, and HDL-cholesterol concentrations, waist circumference, and systolic and diastolic blood pressure. Metabolic syndrome was present in 22% of the men. After adjustment for confounders, total carotenoid and lycopene intakes were inversely associated with presence of metabolic syndrome [relative risk (RR) quartile 4 vs. quartile 1 (95% CI) 0.42 (0.20-0.87), P-trend 0.02; and 0.55 (0.28-1.11), P-trend 0.01, respectively]. For beta-carotene, a decreased risk was observed for each quartile of intake compared with the first [RR quartile 4 vs. quartile 1 (95% CI) 0.58 (0.33-1.02)]. Higher total carotenoid, beta-carotene, alpha-carotene, and lycopene intakes were associated with lower waist circumferences and visceral and subcutaneous fat mass. Higher lycopene intake was related to lower serum triglyceride concentrations. In conclusion, higher total carotenoid intakes, mainly those of beta-carotene and lycopene, were associated with a lower prevalence of metabolic syndrome and with lower measures of adiposity and serum triglyceride concentrations in middle-aged and elderly men.

Common Genetic Variants Highlight the Role of Insulin Resistance and Body Fat Distribution in Type 2 Diabetes, Independent of Obesity

We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp– and oral glucose tolerance test–based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs per allele [95% CI], −0.03 [−0.04, −0.01]; P = 0.004). This score was associated with lower BMI (−0.01 [−0.01, −0.0]; P = 0.02) and gluteofemoral fat mass (−0.03 [−0.05, −0.02; P = 1.4 × 10−6) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and γ-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (Pinteraction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (Pinteraction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.

Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes.

OBJECTIVE To investigate whether dietary phylloquinone and menaquinones intakes are related to risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We used data from a prospective cohort study in 38,094 Dutch men and women, aged 20–70 years. Dietary phylloquinone and menaquinones intakes were assessed using a validated food frequency questionnaire. Diabetes case patients were ascertained mainly via self-report and verified against medical records. RESULTS During 10.3 years of follow-up, 918 incident cases of diabetes were documented. In a multivariate model adjusting for diabetes risk factors and dietary factors, phylloquinone intake tended to be associated (P = 0.08) with a reduced risk of type 2 diabetes with a hazard ratio (HR) of 0.81 (95% CI 0.66–0.99) for the highest versus the lowest quartile. For menaquinones intake, a linear, inverse association (P = 0.038) with risk of type 2 diabetes was observed with an HR of 0.93 (0.87–1.00) for each 10-μg increment in the multivariate model. CONCLUSIONS This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes.

Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-INTERACT Case-Cohort Study

OBJECTIVE The long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from eight European countries, with an average follow-up time of 12.0 years. Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake. RESULTS After adjustment for important diabetes risk factors and dietary factors, the incidence of type 2 diabetes was higher in those with high intake of total protein (per 10 g: HR 1.06 [95% CI 1.02–1.09], Ptrend < 0.001) and animal protein (per 10 g: 1.05 [1.02–1.08], Ptrend = 0.001). Effect modification by sex (P < 0.001) and BMI among women (P < 0.001) was observed. Compared with the overall analyses, associations were stronger in women, more specifically obese women with a BMI >30 kg/m2 (per 10 g animal protein: 1.19 [1.09–1.32]), and nonsignificant in men. Plant protein intake was not associated with type 2 diabetes (per 10 g: 1.04 [0.93–1.16], Ptrend = 0.098). CONCLUSIONS High total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults. In view of the rapidly increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered.