Women with a history of gestational diabetes mellitus (GDM) tend to be insulin-resistant and hyperinsulinemic and are predisposed to the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM). In the evolution of glucose intolerance, the first clinically detectable abnormality has not been defined and the relative importance of contributions of abnormal insulin secretion and insulin resistance is controversial. The present study was performed to evaluate the insulin secretory responses to oral and intravenous glucose and to mixed meals in women with a history of GDM, and to determine if the hyperinsulinemia present in these subjects is appropriate for the degree of insulin resistance. To address these questions, we studied the insulin secretory responses to oral glucose over a 3-hour period and to three mixed meals over a 24-hour period, and quantified the acute insulin response to glucose (AIRglucose) and insulin sensitivity (SI) during frequently sampled intravenous glucose tolerance tests (FSIVGTTs). Studies were performed in seven subjects with a history of GDM and in seven matched controls. Insulin secretion rates (ISRs) were derived by deconvolution of peripheral C-peptide values using a two-compartment model and standard C-peptide kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)