Glucose turnover and gluconeogenesis during pregnancy in women with and without insulin-dependent diabetes mellitus.

OBJECTIVE

To characterize the effect of pregnancy on glucose turnover and gluconeogenesis in healthy women and in women with well-controlled insulin-dependent diabetes mellitus (IDDM).

DESIGN

Prospective clinical study.

SETTING

Clinical research unit of the Hôtel-Dieu de Montréal hospital.

PARTICIPANTS

Five healthy pregnant women and 6 pregnant women with IDDM.

INTERVENTIONS

Glucose turnover and gluconeogenesis in the postabsorptive state at 16 and 32 weeks' gestation and at 24 weeks postpartum were studied with the use of a double stable isotope technique (D[2,3,4,6,6(2)H]-glucose and L[1,2,3(13)C]-alanine). In the women with IDDM, plasma glucose levels were controlled by continuous subcutaneous insulin infusion throughout pregnancy and with a Biostator on the morning of the study.

RESULTS

In the women without IDDM, hepatic glucose production was 11.6 (standard error of the mean [SEM] 2.2) mumol/kg per minute at 16 weeks' gestation, 12.5 (SEM 1.8) mumol/kg per minute at 32 weeks' gestation, and 13.2 (SEM 1.9) mumol/kg per minute at 24 weeks postpartum. In the women with IDDM, it was 10.7 (SEM 2.4) mumol/kg per minute, 10.5 (SEM 1.2) mumol/kg per minute and 12.3 (SEM 0.5) mumol/kg per minute at the same respective periods. The difference in levels between the 2 groups was not significant. Levels of the gluconeogenic precursors alanine and lactate were increased during pregnancy in both the women without IDDM (from 0.18 [SEM 0.02] mmol/L and 0.64 [SEM 0.09] mmol/L, respectively, to 0.25 [SEM 0.02] mmol/L and 1.15 [SEM 0.17] mmol/L, respectively, p < 0.01) and in those with IDDM (from 0.15 [SEM 0.01] mmol/L and 0.47 [SEM 0.04] mmol/L, respectively, to 0.19 [SEM 0.02] mmol/L and 0.70 [SEM 0.01] mmol/L, respectively, p < 0.05). After an overnight fast, gluconeogenesis from alanine was not affected by pregnancy in both groups of women. In the women without IDDM, the plasma insulin level was low in early pregnancy (33.6 [SEM 3.6] pmol/L) and increased in late gestation (87.6 [SEM 9.6] pmol/L) compared with postpartum levels (60.0 [SEM 7.8] pmol/L). Plasma glucagon levels tended to rise in late gestation (from 95.1 [SEM 6.7] ng/L to 116.0 [SEM 36.0] ng/L). In the women with IDDM, the free plasma insulin and plasma glucagon levels were higher in early pregnancy (55.2 [SEM 6.6] pmol/L and 196.1 [SEM 29.8] ng/L, respectively) and did not change significantly during pregnancy.

CONCLUSION

Basal glucose turnover and gluconeogenesis are not increased during pregnancy in women without IDDM or in women with well-controlled IDDM. The decrease in the plasma glucose level during pregnancy suggests that the use of glucose by the growing fetus is augmented and that this is not totally compensated for by a rise in postabsorptive hepatic glucose production. The glucose requirement by the growing fetus is probably supplied by the increased postprandial plasma glucose level.