OBJECTIVE: The purpose of this study was to investigate whether pregnancy induces increased insulin production as a marker of improved beta-cell function in women with long-term type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a prospective study of 90 consecutive pregnant women with type 1 diabetes. At 8, 14, 21, 27, and 33 weeks blood samples were drawn for measurements of A1C, C-peptide, and serum glucose. C-peptide (detection limit: 6 pmol/l) was considered stimulated at a corresponding serum glucose concentration >or=5.0 mmol/l. GAD antibody concentration was determined at 8 and 33 weeks in 35 women. RESULTS: C-peptide concentrations gradually increased throughout pregnancy regardless of serum glucose concentrations in the 90 women with a median duration of diabetes of 17 years (range 1-36 years). Among 35 women with paired recordings of stimulated C-peptide, C-peptide production was detectable in 15 (43%) at 8 weeks and in 34 (97%) at 33 weeks (P < 0.0001), and median C-peptide gradually increased from 6 to 11 pmol/l (P = 0.0004) with a median change of 50% (range -50 to 3,271%) during pregnancy. GAD antibodies were present in 77% with no change from 8 to 33 weeks (P = 0.85). Multivariate regression analysis revealed a positive association between the absolute increase in C-peptide concentrations during pregnancy and decreased A1C from 8 to 33 weeks (P = 0.003). CONCLUSIONS: A pregnancy-induced increase in C-peptide concentrations in women with long-term type 1 diabetes was demonstrated, even in women with undetectable C-peptide concentrations in early pregnancy. This increase is suggestive of improved beta-cell function and was associated with improvement in glycemic control during pregnancy.