The effect of diabetes in pregnancy on leucine turnover and oxidation was examined in 12 insulin-dependent diabetic (IDDM) subjects and 12 gestationally diabetic (GDM) subjects during the third trimester of pregnancy. The data were compared with those in normal pregnant women studied during the same time period and reported previously. Eight of the IDDM subjects were on continuous subcutaneous insulin infusion (insulin pump), and four were on conventional twice-daily insulin treatment. Of the GDM group, seven were on insulin therapy and five were on dietary management. Leucine kinetics were quantified using [1-13C]leucine tracer in combination with respiratory calorimetry and measurement of lean body mass using the H2[18O] dilution method. In addition, glucose kinetics were measured in insulin-treated subjects using [6,62H2]glucose tracer. Despite rigorous metabolic control, fasting plasma glucose (IDDM 5.5 ± 1.9 mmol/L [P < .05], GDM 4.7 ± 1.3 [P < .01], controls 3.6 ± .6, mean ± SD) and hemoglobin A1 ([HbA1] IDDM 7.9 ± 1.9%, GDM 7.5% ± 2.1%) levels were higher in diabetic subjects. Although total insulin levels were higher in insulin-treated diabetic subjects, free-insulin concentrations were similar in all groups. Rates of excretion of urinary urea nitrogen and respiratory quotients were also similar. The rate of glucose turnover was lower in insulin-treated subjects compared with normals. Leucine flux, a measure of the rate of protein breakdown, and leucine oxidation were higher in IDDM and insulin-treated GDM subjects. The rate of leucine oxidation was increased in conventionally managed IDDM and insulin-treated GDM subjects. The increased rate of protein breakdown suggests an increased entry of amino acids into the metabolic pool, which in combination with the normal urea excretion rate, ie, the normal rate of amino acid/protein oxidation, may result in increased availability of amino acids for transplacental flux. Thus, rigorous management of IDDM in pregnancy and of insulin-treated GDM does not normalize whole-body protein breakdown, and may provide an explanation for the persistent fetal morbidity in diabetes in pregnancy.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism