OBJECTIVE To study the natural history of β-cell dysfunction in an individual who developed insulin-dependent diabetes mellitus (IDDM) over a 13-month period while under observation.

RESEARCH DESIGN AND METHODS Insulin secretion rates (ISR) in response to intravenous glucose and mixed meals were estimated by deconvolution of C-peptide levels.

RESULTS When fasting glucose and glycosylated hemoglobin concentrations were still within the normal range, insulin secretory responses to intravenous glucose infusion were reduced, but 80- to 100-min secretory oscillations could still be detected. Sequential glucose infusion studies over a 3-month period demonstrated a progressive reduction in insulin secretion. The tight temporal coupling between ultradian oscillations in ISR and glucose observed in nondiabetic subjects was lost. In response to mixed meals, the oscillatory pattern of secretion was preserved, but the magnitude of the secretory responses was reduced.

CONCLUSIONS Our results indicate that despite the lower absolute secretory rates, ultradian ISR oscillations persist in the period before and immediately after the onset of IDDM in this subject, but they are less tightly coupled to glucose than in nondiabetic subjects.