Plasma Glucose Concentration and Prediction of Future Risk of Type 2 Diabetes

The prevalence of type 2 diabetes has increased in recent decades to epidemic proportions. About 150 million individuals worldwide had type 2 diabetes in 2000, and this number is expected to increase to 300 million by the year 2025 (1). Because of the chronic course of type 2 diabetes and the significant morbidity and mortality associated with the vascular complications of the disease, type 2 diabetes has become not only a serious public health threat, but also a heavy economic burden on the health care system. The total annual cost of diabetes care in the U.S. was estimated to be $175 billion in the year 2007, and this number is expected to increase further with the increasing incidence of the disease (2). Recent clinical trials have reported a reduction in the incidence of type 2 diabetes with lifestyle intervention (3,4) and pharmacotherapy (4,5) in subjects with IGT. These results suggest that primary prevention of type 2 diabetes could be an effective strategy to restrain the epidemic increase in the disease prevalence and reduce the economic burden it poses on the health care system. Accurate identification of subjects at increased risk for future type 2 diabetes is essential for an early prevention program. It minimizes the number of subjects in the intervention program while improving the efficacy and the cost-effectiveness of the intervention. An impaired glucose tolerance (IGT) test was introduced in 1979 as an intermediate state in the transition in glucose homeostasis from normal to overt diabetes (6). Subjects with IGT have increased risk for future type 2 diabetes (7). Thus, all previous intervention trials that have tested the efficacy of prevention strategies have recruited subjects with IGT (3–5). Although, in general, subjects with IGT have an increased risk for future type 2 diabetes, only about half of IGT subjects ultimately convert to diabetes (7). On the other hand, the majority of subjects who develop type 2 diabetes do not have IGT at baseline (8). Therefore, if one relies solely on IGT to identify subjects at risk for future type 2 diabetes, a large fraction of high-risk individuals who do not have IGT and could have benefited from an intervention program would be missed. In this review, we will examine prediction models for future risk of type 2 diabetes and demonstrate that models based on the pathophysiology of the disease have greater prediction value for the future development of type 2 diabetes.