Both insulin resistance and β-cell dysfunction occur during the development of non-insulin-
dependent diabetes mellitus (NIDDM), but controversy exists about which lesion is primary.
Based on longitudinal studies in the Pima Indians, a population with the world's highest
reported prevalence of NIDDM, a two-step model for development of the disease is
proposed. The first step is transition from normal to impaired glucose tolerance, for which
insulin resistance is the main determinant, and the second and later step is worsening from …