We have previously reported a decrease in gluconeogenesis from alanine in normal pregnant women at term gestation as compared with nonpregnant women. In the present study, the effect of diabetes on alanine metabolism was examined in five gestationally diabetic (GDM) women and seven women with type I (insulin-dependent) diabetes (IDDM) during the third trimester of pregnancy. The hemoglobin A1c (HbA1c) concentrations in all subjects were within normal range, indicating good metabolic control. After an overnight fast, each subject was infused simultaneously with L-[2,3, 13C2]alanine and D-[6,6,2H2]glucose tracers as prime constant rate infusion. Plasma alanine and glucose isotopic enrichments were measured by gas chromatography-mass spectrometry. Alanine and glucose turnover rates were quantified by tracer dilution. In five subjects, the contribution of alanine carbon to CO2 was quantified by respiratory calorimetry and by measurement of 13C enrichment of expired CO2. Data from 15 previously reported normal pregnant subjects were used for comparison. The rate of alanine turnover was similar in the GDM and IDDM subjects and was not different from the normal subjects (GDM, 4.6 +/- 1.9; IDDM, 5.4 +/- 2.5; normals, 4.4 +/- 0.8 mumol/kg.min, mean +/- SD). The rate of glucose turnover was significantly reduced (P less than .05) in IDDM as compared with GDM and normal subjects (IDDM, 8.1 +/- 0.8; GDM, 11.5 +/- 3.5; normals, 12.2 +/- 2.2 mumol/kg.min). The contribution of alanine C to glucose C and expired CO2 was similar in the three groups. These data demonstrate that rigorous metabolic control results in normal glucose and alanine metabolism in diabetic pregnancy during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)