Lifestyle and chronic disease epidemiology

Coordinator: Dr. J.W.J. Beulens

JolineChronic diseases like type 2 diabetes, cardiovascular diseases, cancer and depression cause the majority of chronic disease burden in the Netherlands and other western countries. Approximately half of this disease burden can be accounted for by unhealthy behaviours such as smoking, physical inactivity and an unhealthy diet. Such unhealthy behaviours are not only due to individual choices, but also by the 'obesogenic' environment.
The aim of the research line on lifestyle and chronic disease epidemiology is to study patterns and determinants health behaviours. In addition, we investigate how biologic, genetic and environmental determinants lead to such health behaviours and chronic diseases. Finally, interventions are developed to improve a healthy lifestyle and reduce risk of chronic diseases. We identify groups with a high risk to develop chronic diseases to tailor these interventions. We focus on the chronic diseases with the highest disease burden: type 2 diabetes, cardiovascular diseases, cancer and depression, and the following health behaviours: physical inactivity, sedentary behaviour and unhealthy dietary patterns.

Upstream determinants of health behaviours and chronic disease risk

Coordinator: Jeroen Lakerveld, PhD

Sufficient physical activity, low levels of sedentary behaviour and a healthy diet are key lifestyle behaviours for the prevention of chronic diseases such as obesity, type 2 diabetes and cardiovascular disease. Lifestyle behaviour and consequent health status is not only an individual choice but is influenced by contextual -or upstream- factors in our social and physical environments. In western society our social and physical environment often makes it easy to adopt and maintain an unhealthy lifestyle. But what factors -or combination of factors- drive people to unhealthier behaviour? And why are some people more susceptible to environmental influences than others? How do social and physical environmental factors interact with individual characteristics? Answers are essential in order to work towards effective prevention programmes.
In several projects we focus on different contexts, lifestyle behaviours and health outcomes in adults. We are building on the current scientific knowledge and regularly develop new methods and techniques to move beyond the state of the art.

SPOTLIGHT
SPOTLIGHT (Sustainable prevention of obesity through integrated strategies) is a European Commission funded research project that started in 2011. A systems approach was adopted across several independent but inter-related work packages. This was done by identifying mediators of successful outcomes in individual-level obesity interventions, by reviewing the state of evidence on social and physical environmental factors related to obesity, and evaluating the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) of multi-level interventions reported on in the scientific literature, but also of multilevel initiatives that lacked a theoretical basis and were not conducted as part of scientific research. We also conducted qualitative analyses of enhancing and impeding factors relating to these multi-level interventions. Outcomes of work packages were used to inform the design of a cross-European survey and a virtual neighbourhood audit, aimed to gain understanding of the ways in which diverse factors influence the weight status of individuals, underlying obesogenic behaviours, and the social and physical environmental contexts in which they take place, within a cross-European perspective.

ENDEAVOR
ENDEAVOR (Environmental determinants of lifestyle behaviors and risk of type 2 diabetes and cardiovascular diseases).
This project further builds on the New Hoorn Study and the Diabetes Care System. Information on the built environment of participants will be added using geographic information systems (GIS), in order to comprehensively examine determinants of lifestyle behaviours and diabetes risk, depression and cardiovascular disease.

UPSTREAM DETERMINANTS
Upstream determinants of lifestyle behaviours and bood quality. In this project we are collaborating with Sanquin Donor Studies, and focus on environmental determinants of lifestyle behaviours and their effects on blood parameters.

DEDIPAC
DEDIPAC(Determinants of diet and physical activity) is a Knowledge Hub; a multidisciplinary consortium of scientists with currently nearly 300 researchers from 68 research centres in 12 countries across Europe. The objective of the DEDIPAC KH is "to understand the determinants, at both the individual and group levels, regarding dietary, physical activity and sedentary behaviours using a broad multidisciplinary approach, including biological, ecological, psychological, sociological, economic and other socio-economic perspectives and their interrelationships, and to translate this knowledge into a more effective promotion of a healthy diet and physical activity."
The work in DEDIPAC is divided into three Thematic Areas (TAs): TA 1: Assessment and harmonisation of methods for future research, surveillance and monitoring, and evaluation of interventions and policies
TA 2: Determinants of dietary, physical activity and sedentary behaviours across the life course and in vulnerable groups; TA 3: Evaluation and benchmarking of public health and policy interventions aimed at improving dietary, physical activity and sedentary behaviours.

Etiology of overweight and type 2 diabetes

Coordinators: Joline W.J. Beulens, PhD; Prof. J.M. Dekker, MD PhD; Femke Rutters, PhD

DIRECT
DIRECT (DIabetes REsearCh on patient straTification)
Background: the phenotype of people who develop diabetes is highly variable, as is the rate at which their subsequent diabetes progresses, how they respond to diabetes therapy and who develops micro- and macrovascular complications. This heterogeneity forms a major barrier to effective patient management at the individual level. Type 2 diabetes is typified by a progressive deterioration in glycaemic control with time. A reliable biomarker that can be used to predict the trajectory of future glycaemic progression would help to identify subtypes of diabetes and in particular could help to inform individualised therapeutic selection and management.

Aim: to identify biomarkers that define sub-classes of individuals at risk for type 2 diabetes and thus facilitate targeted diabetes prevention and/or treatment by identifying therapeutic targets that are more prevalent in some subgroups of the studied population.

Methods
Study design: Prospective cohort study.
Study population: We will re-invite the RISC, HOM and New Hoorn Study population of whom 500 subjects at high-risk of type 2 diabetes will be followed-up repeatedly until 2018. Additionally, 167 subjects with diabetes type 2 (age >35 and <70, white European) will be recruited from the Diabetes Care System Westfriesland and will be followed-up repeatedly until 2014.
Study protocol: A detailed baseline phenotyping will be conducted and repeated at 18 months follow-up and 36 months follow-up (the latter only in subjects at risk for developing diabetes). The subjects will undergo several examinations, including am oral glucose test or a mixed meal tolerance test and a MRI scan to assess pancreatic, abdominal and liver fat. In addition, faecal and toenail samples will be collected for the measurement of microbiotica and trace elements. Urinary C-peptide excretion rates (subjects with diabetes) and HbA1c blood spot (subjects at risk for developing diabetes) will be measured periodically to assess the rate of glycaemic deterioration.

The (New) Hoorn Study
The (New) Hoorn Study: prevalence and determinants of impaired glucose regulation.

Background:
In 1989 a large study on the prevalence of type 2 diabetes and impaired glucose tolerance in the general population of the Netherlands was performed (The Hoorn Study). Results showed that the prevalence of known and newly-detected diabetes and impaired glucose tolerance in the 2484 participants was 3.6%, 4.8% and 10.3% respectively. Age, family history of diabetes and waist-to-hip ratio (WHR) were the most important determinants of glucose metabolism. Due to various lifestyle changes, the prevalence of diabetes type 2 increased worldwide since 1989. Despite these changes, no large population-studies aimed to determine the prevalence of impaired glucose regulation and determinants of type 2 diabetes in the Netherlands have been carried out in the last 15 years. Therefore, in 2006 a new cohort study on diabetes in the Netherlands was constructed: the New Hoorn studies. Both cohorts have and will be followed for several years to study the longitudinal relations between several risk factors and diabetes.

Aims
1. To study the prevalence of impaired glucose regulation and type 2 diabetes in the general population aged 40 to 65 years, and to compare these prevalence rates between the two Hoorn Study cohorts.
2. To study differences in various anthropometric and metabolic population characteristics (with special attention to lifestyle factors and body composition) between subgroups with a different glucose status and between the first and new Hoorn Study
3. To study differences in cardiovascular risk profile in participants of the Hoorn Study and New Hoorn Study.

Methods
Study design: Prospective cohort studies
Study population: In 1989 and in 2006, random samples, aged 40-76, were drawn from the municipal registry of Hoorn; of whom 2484 and 2807 persons agreed to participate.
Study protocol: all participants visited the research centre in Hoorn in a fasting state. The following procedures were assessed during this visit, first anthropometry including height, weight, waist circumference and hip circumference and blood pressure measurements. Second, a 2-point Oral Glucose Tolerance Test (OGTT) , with blood draws at 0 en 120 minutes after glucose ingestion. Blood samples of both time points were used for determination of plasma glucose. In addition, from the fasting blood sample, triglycerides, total and HDL-cholesterol and HbA1c were determined. Third, h lifestyle measurements including habitual physical activity (SQUASH), food consumption (FFQ), smoking, alcohol intake, employment, education, marital status, current medication use, disease history, family history of disease, depression (CES-D), anxiety (HADS), perceived general health (SF-36) and self-reported birth weight were determined using questionnaires. Finally, all participants also gave written informed consent to collect data on morbidity and mortality from their medical records in the future.

Cancer Epidemiology

Coordinator: Laurien Buffart, PhD

Advances in early detection and treatment of cancer have improved survival rates over the past decades, with approximately 60% of patients living over 5 years after diagnosis. However, cancer and its treatment are often associated with physical and psychosocial problems .

Physical activity and exercise during and after cancer treatment has beneficial effects on a number of physical and psychosocial outcomes, including increased aerobic fitness, muscle strength and qualtiy of life and reduced fatigue and depression. Given the beneficial effects, exercise guidelines for patients with cancer suggest that exercise should be an integral and continuous part of care for all patients. The further development and specification of recommended exercise prescriptions has been limited by the type of research conducted.

We hypothesize that a personalised and tailored exercise prescriptions will lead to better outcomes than a one-size fits all approach. Therefore, we aim to get a better understanding of which exercise intervention in terms of frequency, intensity, type, and time (FITT) is beneficial, for whom, under what circumstances (e.g. identify demographic, clinical, personal moderators of intervention effects), and for which specific health outcome. Important health outcomes include specific symptoms (e.g. fatigue, nausea, pain, cachexia), toxicities (e.g. cardiotoxicity, neuropathy), quality of life, and (progression free) survival.

Our research on physical activity and cancer survivorship focuses on understanding:
1) What exercise intervention (in terms of FITT factors) works for whom, and under what circumstances
2) Underlying mechanisms of the effects of exercise on health outcomes (e.g. symptoms, toxicities, quality of life and survival)
3) How to reach, motivate and enable patients with cancer to obtain and maintain a physically active lifestyle.

Main research projects are A-CaRe, POLARIS and METRIC.

A-CaRe
Alpe d'HuZes Cancer Rehabilitation (A-CaRe): A-CaRe evaluates the effectiveness and cost-effectiveness of various physical activity and exercise interventions on physical fitness, fatigue and quality of life in several groups of cancer patients: 1) after chemotherapy, the REACT study; 2) during chemotherapy, the PACES study; 3) after stem cell transplantation, the EXIST study; and 4) in children with cancer, the QLIM study. (www.a-care.org).

POLARIS
Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study. POLARIS aims to build an internationally shared database to conduct an individual patient data meta-analysis to study the effect of physical activity and supportive care interventions on quality of life among cancer patients and survivors, to study which intervention works for whom and under what circumstances (identification of moderators) and via what mechanisms (identification of mediators), to be able to predict the most effective intervention for individual patients (www.polaris-study.org).

METRIC
MEchanisms of Training In Cancer (METRIC) study. METRIC is a pilot study exploring the role of the muscular, immune, and endocrine system in the exercise effect on fatigue during chemotherapy treatment in breast and colon cancer survivors.

Cardiovascular disease epidemiology

Coordinator: Joline W.J. Beulens, PhD

Cardiovascular diseases are amongst the most important chronic diseases in the Netherlands. People with type 2 diabetes remain at an approximately 2-fold increased risk of developing cardiovascular diseases. In addition, the prevalence of heart failure is rising in this group, especially heart failure with preserved ejection fraction. We investigate the relation of lifestyle factors, biologic and genetic factors with cardiovascular diseases among people with type 2 diabetes. This research is mainly conducted in the Hoorn cohorts and the Hoorn Diabetes Care System cohort, in close collaboration with the department of general practice. The Hoorn Diabetes Care System cohort is a registration of all people with diabetes living in the area of West-Friesland. More information can be found on the website.

ARTEMIS
Vascular calcifications are associated with a 3- to 4-fold increased risk of cardiovascular diseases and are present in about 70% of diabetes patients. However, diabetes patients develop a specific form of vascular calcifications, not in the intima, but in the tunica media (medial calcifications). Studies suggest both forms of calcifications are distinct mechanisms leading to (different) cardiovascular outcomes. However, medial and intimal calcification are hardly distinguished in clinical research or practice. This study aims to investigate the risk factors and vascular consequences of intimal and medial calcifications in patients with type 2 diabetes in the Hoorn Diabetes Care System cohort. The study is funded by the Netherlands Heart Foundation and conducted in close collaboration with the Julius Center, University Medical Center Utrecht.

EARLY-HFPEF
Heart failure (HF) is a clinical syndrome with a worldwide increasing prevalence, a very high morbidity and mortality. Approximately 1-2 % of the adult population in developed countries has HF, with the prevalence rising to more than 10 % among persons 70 years of age or older. It is now well established that among HF patients, approximately half have preserved systolic function, also known as HF with preserved ejection fraction (HFPEF). HFpEF is highly prevalent in elderly women and frequently accompanied by co-morbidities such as obesity, metabolic syndrome, type 2 diabetes mellitus. Despite this, no strategies are available for early detection of HFPEF. The current collaboration aims to find diagnostic and prognostic clues to allow early detection of HFPEF. The project is funded by Cardiovasculair Onderzoek Nederland (CVON) and conducted in close collaboration with Prof. Paulus (VUmc, department of physiology) and Prof. Heymans (Maastricht University Medical Center).

RHAPSODY
RHAPSODY is a IMI funded consortium comprising 26 partners across Europe, including academic partners and industry. The project aims to identify new molecular biomarkers of pre-diabetes and T2D development and to define a molecular taxonomy of type 2 diabetes mellitus. Newly identified biomarkers will improve monitoring progression of the prediabetic state to T2D and allow improved patient stratification. To achieve this, it combines existing data from multiple large prospective (pre-) diabetic cohorts across Europe. Genetics, genomics, clinical, and biochemical data is stored in a federated database that allows modeling of the data at a consortium-wide level.

Lifestyle and chronic disease epidemiology