The Natural History of Progression From Normal Glucose Tolerance to Type 2 Diabetes in the Baltimore Longitudinal Study of Aging

The natural history of progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes is not well defined. We studied this progression using biennial oral glucose tolerance tests performed in the Baltimore Longitudinal Study of Aging and survival analysis to assess progression from NGT to abnormal fasting plasma glucose (FPG; ≥6.1 mmol/l), abnormal 2-h plasma glucose (2hPG; ≥7.8 mmol/l), IFG (FPG 6.1–6.9 mmol/l, 2hPG ≤7.8 mmol/l), and IGT (FPG <6.1 mmol/l, 2hPG 7.8–11.0 mmol/l), and from IFG-IGT to diabetes (FPG ≥7.0 mmol/l or 2hPG ≥11.1 mmol/l). At baseline, the 815 subjects had a mean age of 57 years, 35% were women, and 60% had NGT. Of the 488 subjects with NGT, over half were followed for at least 10 years. By 10 years, 14% had progressed to abnormal FPG and 48% to abnormal 2hPG. Of the 267 subjects who progressed to IFG-IGT, 216 had additional follow-up. By 10 years, 8% of these progressed to diabetes by FPG whereas 27% progressed by 2hPG. In subsidiary analyses, we defined “abnormal” FPG as ≥5.55 mmol/l and “diabetic” FPG as ≥6.1 mmol/l, making the baseline prevalence of IFG similar to that of IGT. By these criteria, 43% progressed to abnormal FPG and 43% to abnormal 2hPG by 10 years of follow-up; among subjects developing impaired FPG or 2hPG, 22% progressed to diabetes by FPG whereas 17% progressed by 2hPG at 10 years. Nonetheless, 42% of subjects developing abnormal FPG did not develop abnormal 2hPG, and vice versa. We conclude that, although phenotypic differences in rates of progression are partly a function of diagnostic thresholds, fasting and postchallenge hyperglycemia may represent phenotypes with distinct natural histories in the evolution of type 2 diabetes.