THE EPIDEMIC OF DIABETES HAS TAKEN HOLD AND IS EXtending to new populations. The prevalence of type 2 diabetes in children and in developing nations has increased dramatically, and adult-onset type 1 diabetes is now well recognized. Diabetic cardiovascular disease has become a worldwide burden. While new cases of heart disease and cancer are stable or decreasing, the incidence of diabetes has increased 6% annually in the United States and more than that in developing countries. The human and economic toll of diabetes increases correspondingly, and this requires an integrated, global response. However, policy makers, insurance companies, and the general public are just beginning to recognize the seriousness of diabetes. Opportunities for progress are virtually limitless, with some of the most fundamental questions raised by diabetes remaining unanswered: What underlies the metabolic syndrome? What exactly mediates the link between obesity and insulin resistance? Can this resistance be overcome pharmacologically? What triggers the process that destroys beta cells in type 1 diabetes? How can that process be prevented? Can the enormous potential of cell therapy and mechanical insulin delivery be realized? How can individuals with diabetes be motivated to follow self-care patterns necessary to prevent complications? How can an entire society be motivated to decrease its food consumption? How can prevention be paid for while reducing the total cost of diabetes care? The articles in this theme issue of THE JOURNAL address important questions in diabetes today, and also illustrate some of the newer methods being applied to diabetes research. Just as new techniques undergird the advances in basic science, so they also enhance clinical research. This issue includes reports from a large community observational cohort study, linked state and hospital databases, a computerbased patient record review, a cost-effectiveness analysis, 2 randomized controlled trials, and long-term follow-up of an important clinical study. There is keen interest in the events that precede diabetes, and researchers are seeking to discover diabetogenic genes. The thrifty gene hypothesis postulates that some individuals store fat more efficiently, adapting well to periods of starvation, but poorly to times of plenty. This concept is undoubtedly oversimplified—type 2 diabetes is polygenic. Moreover, it is possible that the multiple genes may express themselves through such nontraditional phenotypes as susceptibility to obesity from dysregulation of appetite. A related area of interest is the “minienvironment of the uterus,” and the role that early imprinting can have on later life. The study by Innes and colleagues examines whether a woman’s birth weight influences her risk of developing gestational diabetes, which is a marker for risk of type 2 diabetes. Linking hospital discharge data to state vital records, the authors report that women with lower birth weights as newborns were more likely to develop gestational diabetes. This finding is consistent with results obtained under extremely different circumstances— pregnant women in the Netherlands during a fixed period of Nazi-imposed famine during World War II gave birth to offspring that were predisposed to type 2 diabetes. In a longitudinal community observational study, Wong and colleagues made the surprising observation of an association between retinal arteriolar narrowing and the risk of incident diabetes. The implication is that diabetes not only causes, but may be caused by, microvascular disease. These results call to mind the work of Siperstein and colleagues in the 1960s and 1970s, which suggested capillary basement membrane thickening precedes the onset of diabetes. Studies of patients prior to the diagnosis of diabetes raise the potential for primary prevention, while improved management of diabetes could prevent complications. Davies and colleagues studied what might be considered an unlikely insulin sensitizer—alcohol. In a randomized, controlled, crossover study of healthy postmenopausal women, the authors found improved insulin sensitivity