Epidemic of diabetes, affecting about 3–5% of Western populations, is one of the main threats to human health in the 21st century (1). Changes in the human environment, behavior, and lifestyle have resulted in a dramatic increase in the incidence and prevalence of diabetes in people with genetic susceptibility to diabetes. The global number of people with diabetes was 151 million in 2000, and it is projected to increase to 221 million in 2010 (an increase of 46%) both in developed and developing countries (2). Chronic hyperglycemia leads to many long-term complications in the eyes, kidneys, nerves, heart, and blood vessels. Individuals with pre-diabetes, undiagnosed type 2 diabetes, and long-lasting type 2 diabetes are at high risk of all complications of macrovascular disease, coronary heart disease (CHD), stroke, and peripheral vascular disease. More than 70% of patients with type 2 diabetes die of cardiovascular causes (3). Therefore, the epidemic of type 2 diabetes will be followed by an epidemic of diabetes-related cardiovascular disease (CVD). Over the years, epidemiological studies have produced important information on the prevalence and incidence of diabetes complications in different populations. They have also given important information on different risk factors determining susceptibility to diabetes complications (Fig. 1). This information is crucial for mechanistic studies in physiology at the tissue level and for molecular biology studies at the cellular level. A good example is glycated hemoglobin. Several studies have indicated that glycated hemoglobin is associated with diabetes complications in prospective epidemiological studies. That information has been crucial for the planning of clinical trials to test the hypothesis that the treatment of chronic hyperglycemia leads to reduction in long-term diabetes complications. Moreover, information from epidemiology has led to several mechanistic studies and the elucidation of molecular level insights how insulin resistance and hyperglycemia lead to diabetes complications.