OBJECTIVE: That type 2 diabetes is associated with the metabolic syndrome is known. However, information is lacking regarding the long-term and adverse changes of metabolic syndrome variables in the development of type 2 diabetes from childhood to adulthood. RESEARCH DESIGN AND METHODS: Observations were examined, retrospectively, in a community-based cohort of normoglycemic (n = 1,838), pre-diabetic (n = 90), and type 2 diabetic (n = 60) subjects followed serially for cardiovascular risk factors during childhood (4-11 years), adolescence (12-18 years), and adulthood (19-44 years). RESULTS: Diabetic subjects versus normoglycemic subjects had significantly higher levels of subscapular skinfold, BMI, triglycerides, glucose, insulin, and homeostasis model assessment of insulin resistance and lower levels of HDL cholesterol beginning in childhood and higher levels of mean arterial pressure (MAP) in adolescence and adulthood. In a multivariate model including BMI, MAP, HDL cholesterol, LDL cholesterol, triglycerides, glucose, and insulin, adjusted for age, age(2), race, sex, and race x sex interaction, adverse changes in glucose and LDL cholesterol were independently associated with pre-diabetic subjects, whereas adverse changes in BMI, glucose, and HDL cholesterol were associated with diabetic subjects. As young adults, pre-diabetic and diabetic groups displayed a significantly higher prevalence of obesity, hypertension, dyslipidemia, hyperinsulinemia, and metabolic syndrome. CONCLUSIONS: These findings indicate that adverse levels of risk variables of metabolic syndrome, adiposity, and measures of glucose homeostasis accelerating since childhood characterize the early natural history of type 2 diabetes and underscore the importance of early prevention and intervention on risk factors beginning in childhood.