Environmental risk factors of type 2 diabetes-an exposome approach

Type 2 diabetes is one of the major chronic diseases accounting for a substantial proportion of disease burden in Western countries. The majority of the burden of type 2 diabetes is attributed to environmental risks and modifiable risk factors such as lifestyle. The environment we live in, and changes to it, can thus contribute substantially to the prevention of type 2 diabetes at a population level. The ‘exposome’ represents the (measurable) totality of environmental, i.e. nongenetic, drivers of health and disease. The external exposome comprises aspects of the built environment, the social environment, the physico-chemical environment and the lifestyle/food environment. The internal exposome comprises measurements at the epigenetic, transcript, proteome, microbiome or metabolome level to study either the exposures directly, the imprints these exposures leave in the biological system, the potential of the body to combat environmental insults and/or the biology itself. In this review, we describe the evidence for environmental risk factors of type 2 diabetes, focusing on both the general external exposome and imprints of this on the internal exposome. Studies provided established associations of air pollution, residential noise and area-level socioeconomic deprivation with an increased risk of type 2 diabetes, while neighbourhood walkability and green space are consistently associated with a reduced risk of type 2 diabetes. There is little or inconsistent evidence on the contribution of the food environment, other aspects of the social environment and outdoor temperature. These environmental factors are thought to affect type 2 diabetes risk mainly through mechanisms incorporating lifestyle factors such as physical activity or diet, the microbiome, inflammation or chronic stress. To further assess causality of these associations, future studies should focus on investigating the longitudinal effects of our environment (and changes to it) in relation to type 2 diabetes risk and whether these associations are explained by these proposed mechanisms. Graphical abstract: [Figure not available: see fulltext.

Spouses, social networks and other upstream determinants of type 2 diabetes mellitus

Diabetes risk factors outside the individual are receiving increasing attention. In this issue of Diabetologia, Nielsen et al (DOI: https://doi.org/10.1007/s00125-018-4587-1 ) demonstrate that an individual's obesity level is associated with incident type 2 diabetes in their spouse. This is in line with studies providing evidence for spousal and peer similarities in lifestyle behaviours and obesity. Non-random mating and convergence over time are two explanations for this phenomenon, but shared exposure to more upstream drivers of diabetes may also play a role. From a systems-science perspective, these mechanisms are likely to occur simultaneously and interactively as part of a complex system. In this commentary, we provide an overview of the wider system-level factors that contribute to type 2 diabetes

Recent changes in the Dutch foodscape: socioeconomic and urban-rural differences.

BACKGROUND: Obesogenic food environments may influence dietary behaviours and contribute to obesity. Few countries quantified changes in their foodscape. We explored how the availability of different types of food retailers has changed in the Netherlands across levels of neighbourhood socioeconomic status (SES) and urbanisation. METHODS: This longitudinal ecological study conducted in the Netherlands had as unit of analysis administrative neighbourhoods. From 2004 to 2018, the geographic location and type of each food retailer were objectively assessed by a commercial company. Food retailers were categorised as local food shops, fast food restaurants, food delivery, restaurants, supermarkets, and convenience stores. Information on neighbourhood SES and urbanisation was obtained from Central Bureau of Statistics (CBS). To test the change in the counts of food retailers we used negative binomial generalized estimating equations (GEE), with neighbourhoods as the group variable, time as the independent variable and the counts of each type of food retailer as outcome. To account for changes in population density, analyses were adjusted for the number of inhabitants per neighbourhood. We tested effect modification by adding an interaction term for neighbourhood SES and urbanisation to the models. RESULTS: In Dutch neighbourhoods between 2004 and 2018, a 120 and 35% increase was found in the count of food delivery outlets and restaurants, respectively, and a 24% decrease in count of local food shops. Stratified analyses showed an increase in the availability of supermarkets and convenience stores in the more urbanised and lower SES neighbourhoods, while a decrease was observed in the less urbanised and higher SES neighbourhoods. CONCLUSIONS: We observed considerable changes in the Dutch foodscape. Over a 14 years period, the foodscape changed towards a higher availability of food retailers offering convenience and ready-to-eat foods. These findings can help policy makers aiming to promote a healthier food environment and obesity prevention

The longitudinal association between chronic stress and (visceral) obesity over seven years in the general population: The Hoorn Studies.

In total, 2416 participants with a mean age of 56.1 (±7.3) years, of which 51.4% were women, and 12.5% had a lower educational level from the Hoorn studies were followed for seven years. Stress was measured with a 'Serious Life Events' questionnaire, which was summed into a total score (range zero to ten events) and stratified to account for nonlinearity. Changes in visceral obesity were assessed by changes in BMI (kg/m2) and waist circumference (cm) in seven years. We used the product of coefficient approach to assess mediation of the following lifestyle factors: diet, physical activity, smoking, and alcohol intake. We analyzed associations between stressful life events and change in BMI and waist circumference with linear regression models

The longitudinal association between chronic stress and (visceral) obesity over seven years in the general population: The Hoorn Studies

Background: We aimed to study the mediating role of diet quality, physical activity, smoking, and alcohol intake in the association of stressful life events with visceral obesity over a seven-year period and assessed effect modification by sex and SES. Methods: In total, 2416 participants with a mean age of 56.1 (±7.3) years, of which 51.4% were women, and 12.5% had a lower educational level from the Hoorn studies were followed for seven years. Stress was measured with a ‘Serious Life Events’ questionnaire, which was summed into a total score (range zero to ten events) and stratified to account for nonlinearity. Changes in visceral obesity were assessed by changes in BMI (kg/m2) and waist circumference (cm) in seven years. We used the product of coefficient approach to assess mediation of the following lifestyle factors: diet, physical activity, smoking, and alcohol intake. We analyzed associations between stressful life events and change in BMI and waist circumference with linear regression models. Results: Within the low education group, we observed a significant association between ≥3 stressful life events and a change in BMI (0.60 kg/m2 (CI: 0.05, 1.14)) and waist circumference (2.23 cm (CI: 0.19, 4.48)), compared to experiencing no events. For both BMI and waist circumference, no significant associations were observed when experiencing 1 or 2 events. In the moderate to high education group, we observed only statistically significant associations for waist circumference when experiencing ≥3 stressful life events (0.86 cm (CI: 0.05, 1.41)) and not for the other event groups. Our mediation analyses showed that the proportion mediated by smoking was 13.2%, while the other lifestyle factors showed no mediating effect. Conclusions: Multiple stressful life events are associated with an increase in waist circumference and BMI in those with lower education. Smoking might play a mediating role in this association

Phenotypic and lifestyle determinants of HbA1c in the general population-The Hoorn Study

AIM: To investigate the relative contribution of phenotypic and lifestyle factors to HbA1c, independent of fasting plasma glucose (FPG) and 2h post-load glucose (2hPG), in the general population. METHODS: The study populations included 2309 participants without known diabetes from the first wave of the Hoorn Study (1989) and 2619 from the second wave (2006). Multivariate linear regression models were used to analyze the relationship between potential determinants and HbA1c in addition to FPG and 2hPG. The multivariate model was derived in the first wave of the Hoorn Study, and replicated in the second wave. RESULTS: In both cohorts, independent of FPG and 2hPG, higher age, female sex, larger waist circumference, and smoking were associated with a higher HbA1c level. Larger hip circumference, higher BMI, higher alcohol consumption and vitamin C intake were associated with a lower HbA1c level. FPG and 2hPG together explained 41.0% (first wave) and 53.0% (second wave) of the total variance in HbA1c. The combination of phenotypic and lifestyle determinants additionally explained 5.7% (first wave) and 3.9% (second wave). CONCLUSIONS: This study suggests that, independent of glucose, phenotypic and lifestyle factors are associated with HbA1c, but the contribution is relatively small. These findings contribute to a better understanding of the low correlation between glucose levels and HbA1c in the general population

Phenotypic and lifestyle determinants of HbA1c in the general population-The Hoorn Study.

AIM:To investigate the relative contribution of phenotypic and lifestyle factors to HbA1c, independent of fasting plasma glucose (FPG) and 2h post-load glucose (2hPG), in the general population. METHODS:The study populations included 2309 participants without known diabetes from the first wave of the Hoorn Study (1989) and 2619 from the second wave (2006). Multivariate linear regression models were used to analyze the relationship between potential determinants and HbA1c in addition to FPG and 2hPG. The multivariate model was derived in the first wave of the Hoorn Study, and replicated in the second wave. RESULTS:In both cohorts, independent of FPG and 2hPG, higher age, female sex, larger waist circumference, and smoking were associated with a higher HbA1c level. Larger hip circumference, higher BMI, higher alcohol consumption and vitamin C intake were associated with a lower HbA1c level. FPG and 2hPG together explained 41.0% (first wave) and 53.0% (second wave) of the total variance in HbA1c. The combination of phenotypic and lifestyle determinants additionally explained 5.7% (first wave) and 3.9% (second wave). CONCLUSIONS:This study suggests that, independent of glucose, phenotypic and lifestyle factors are associated with HbA1c, but the contribution is relatively small. These findings contribute to a better understanding of the low correlation between glucose levels and HbA1c in the general population

Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer

Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall survival. In 67 patients with mCRC (mean age ± standard deviation, 66.4 ± 10.6 years; 63% male), muscle area (square centimeters) was assessed using computed tomography scans of the third lumbar vertebra before and during palliative chemotherapy. Treatment modifications resulting from toxicity were evaluated, including delay, dose reduction, or termination of chemotherapy. Multiple regression analyses were performed for the association between change in muscle area and treatment modification and secondly overall survival. Muscle area of patients with mCRC decreased significantly during 3 months of chemotherapy by 6.1% (95% CI, -8.4 to -3.8; P <.001). Change in muscle area was not associated with treatment modifications. However, patients with muscle loss during treatment of 9% or more (lowest tertile) had significantly lower survival rates than patients with muscle loss of less than 9% (at 6 months, 33% v 69% of patients alive; at 1 year, 17% v 49% of patients alive; log-rank P = .001). Muscle loss of 9% or more remained independently associated with survival when adjusted for sex, age, baseline lactate dehydrogenase concentration, comorbidity, mono-organ or multiorgan metastases, treatment line, and tumor progression at first evaluation by computed tomography scan (hazard ratio, 4.47; 95% CI, 2.21 to 9.05; P <.001). Muscle area decreased significantly during chemotherapy and was independently associated with survival in patients with mCRC. Further clinical evaluation is required to determine whether nutritional interventions and exercise training may preserve muscle area and thereby improve outcom

The association between population density and blood lipid levels in Dutch blood donors.

BACKGROUND: In low and middle-income countries (LMIC), the total and LDL cholesterol and triglyceride levels of residents of urban areas are reported to be higher than those of rural areas. This may be due to differences in lifestyle behaviors between residents of urban areas and rural areas in LMIC. In this study, our aims were to (1) examine whether or not LDL cholesterol, total/HDL ratios and triglyceride levels of individuals in densely populated areas are higher than those of individuals living in less-densely populated areas in a high-income country (HIC) and (2) investigate the potential mediating roles of physical activity and sedentary behavior. METHODS: We used cross-sectional data from 2547 Dutch blood donors that participated in Donor InSight-III. Linear regression was used to analyze the association between population density and LDL cholesterol, total/HDL cholesterol ratio and HDL cholesterol. The mediating roles of moderate-to-vigorous physical activity (MVPA) and sedentary behavior were investigated in a subsample (n = 740) for which objectively measured MVPA/sedentary behavior data was available. Multiple mediation with linear regression analyses were performed and the product-of-coefficients method was used to calculate direct and indirect effects. RESULTS: Mean LDL cholesterol and median total cholesterol/HDL cholesterol ratio and triglyceride levels were 2.89, 3.43 and 1.29 mmol/L, respectively. Population density was not associated with LDL cholesterol [β 0.00 (- 0.01; 0.01)], log transformed total/HDL cholesterol ratio [β 1.00 (1.00; 1.00)] and triglyceride levels [β 1.00 (0.99; 1.00)]. No statistically significant direct or indirect effects were found. CONCLUSION: Contrary to previous findings in LMIC, no evidence was found that population density is associated with blood lipid levels in blood donors in the Netherlands or that MVPA and sedentary behavior mediate this association. This may be the result of socioeconomic differences and, in part, may be due to the good health of the study population and the relatively high population density in the Netherlands. Also, compared to LMIC, differences in physical activity levels in more versus less populated areas may be less pronounced in HIC

Vitamin K intake and all-cause and cause specific mortality

BACKGROUND & AIMS: Vitamin K has been associated with various health outcomes, including non-fatal cardiovascular diseases (CVD) and cancer. However, little is known about the association between vitamin K intake and all-cause and cause specific mortality. This study aims to investigate the association between vitamin K intake and all-cause and cause-specific mortality. METHODS: This prospective cohort study included 33,289 participants from the EPIC-NL cohort, aged 20-70 years at baseline and recruited between 1993 and 1997. Dietary intake was assessed at baseline with a validated food frequency questionnaire and intakes of phylloquinone, and total, short chain and long chain menaquinones were calculated. Information on vital status and causes of death was obtained through linkage to several registries. The association between the different forms of vitamin K intake and mortality was assessed with Cox proportional hazards, adjusted for risk factors for chronic diseases and nutrient intake. RESULTS: During a mean follow-up of 16.8 years, 2863 deaths occurred, including 625 from CVD (256 from coronary heart disease (CHD)), 1346 from cancer and 892 from other causes. After multivariable adjustment, phylloquinone and menaquinones were not associated with all-cause mortality with hazard ratios for the upper vs. the lowest quartile of intake of 1.04 (0.92;1.17) and 0.94 (0.82;1.07) respectively. Neither phylloquinone intake nor menaquinone intake was associated with risk of CVD mortality. Higher intake of long chain menaquinones was borderline significantly associated (ptrend = 0.06) with lower CHD mortality with a HR10μg of 0.86 (0.74;1.00). None of the forms of vitamin K intake were associated with cancer mortality or mortality from other causes. CONCLUSIONS: Vitamin K intake was not associated with all-cause mortality, cancer mortality and mortality from other causes