Diabetes is already one of the most common chronic diseases in the Dutch population and a substantial further increase in the number of people with diabetes is expected in the near future. A large part of the burden of diabetes can be ascribed to the cardiovascular complications of diabetes which affect quality of life, as well as life expectancy of the patients. In this thesis we explore the opportunities to reduce the future burden of diabetes and cardiovascular diabetes complications in the Dutch population, through prevention. These opportunities depend on the existence of modifiable risk factors for diabetes and the availability of interventions aimed at reducing the incidence of diabetes or diabetes complications. In this thesis we consider the role of weight change, alcohol consumption and smoking as risk factors for diabetes and the cost-effectiveness of preventive interventions in different target populations.Body Mass Index (BMI) is acknowledged as an important modifiable risk factor for diabetes but the role of weight change is not so clear. We showed that, conditional upon initial weight, people who gained weight, had an increased risk of diabetes, compared to persons with relatively stable weight. If adjusted for initial BMI, 5-years weight change was a significant risk factor for diabetes (OR 1.08, 95% CI: 1.04, 1.13 per kg weight change). There was no association between weight change and diabetes incidence, if the association was adjusted for attained BMI (OR 0.99, 95% CI 0.94, 1.04 per kg weight change). We concluded that weight change appears to have no effect on diabetes incidence, beyond its effect on attained BMI.In previous studies, smoking has been reported to increase diabetes risk, while for alcohol consumption the lowest risk for diabetes is generally observed for people who drink moderately. We assessed the associations between these, potentially modifiable, risk factors and diabetes incidence in a Dutch population. We found a u-shaped association between alcohol consumption and diabetes incidence in Dutch women, with the lowest risk for moderate drinkers (1 or 2 drinks per day). We found no evidence for a significant association between alcohol consumption and diabetes incidence in Dutch men. Smoking more than 10 cigarettes per day tended to increase diabetes risk in both men and women, but the associations were not statistically significant.There is substantial evidence that lifestyle interventions focused at improved diet and physical exercise are cost-effective in persons at high risk of developing diabetes. However, the cost-effectiveness of these interventions in other target populations was relatively unknown. We explored the potential long-term health effects and cost-effectiveness of two types of lifestyle interventions: a community-based intervention, targeted at the general Dutch population, and an individual-based intervention, targeted at obese Dutch adults. The long-term effects of these interventions were simulated with a computer-based model: the Chronic Diseases Model (CDM). We showed that the 20-year cumulative incidence of diabetes could be reduced by 0.5-2.4% through large-scale implementation of a community-based intervention, and by 0.4-1.6%, through an individual based intervention for obese adults. Both interventions were projected to reduce lifetime diabetes-related medical costs, but total health care costs increased. The cost-effectiveness ratios ranged from €3,100 to €3,900 per quality adjusted life year (QALY) for the community-based intervention, and from €3,900 to €5,500 per QALY for the individual-based intervention, which means that both interventions are cost-effective according to general standards.We also assessed the potential health effects and cost-effectiveness of seven selected lifestyle interventions for Dutch diabetes patients. Again, long-term effects were simulated with the CDM. There was a large variation in effectiveness between the seven interventions. The reductions in cumulative lifetime incidence of cardiovascular complications among participants ranged from 0.1% to 6.1%. The most effective intervention was a two year structured counseling program, aimed to increase physical activity in inactive diabetes patients. The intervention costs ranged from €124 to €584 per participant, and the cost-effectiveness ratios ranged from €10,000 to €39,000 per QALY. The impact of uncertainty in intervention costs, intervention effects, and long-term maintenance of effects, were quantified with probabilistic sensitivity analyses. These analyses revealed, that four out of seven interventions had a high probability to be very cost-effective.Besides lifestyle, appropriate medication contributes to the prevention of complications in diabetes patients. Guidelines for cardiovascular management recommend lipid lowering treatment for nearly all patients with diabetes. However, in Dutch current practice (in 2007) ‘only’ about 1 out of 3 patients received this treatment. We modeled the long-term effects on cardiovascular complications in the Dutch diabetes population, under the assumption that all patient would use lipid-lowering medication (statins). We showed that treatment for all patients (compared to current care) reduced the life-time cumulative incidence of cardiovascular complications in the Dutch diabetic population by approximately seven percent. With more realistic assumptions about effectiveness and participation, the cumulative incidence of cardiovascular complications decreased by approximately two percent.We conclude that lifestyle interventions can be cost-effective in divers target populations, including diabetes patients. Large-scale implementation of these interventions is justified, and required in order to reduce the future burden of diabetes. However, since the impact on population health, achieved through these interventions, is expected to be moderate, additional research should aim to improve currently available interventions. Simultaneously, opportunities for alternative approaches to the prevention of diabetes and its complications should be further explored.