Glucose and Amino Acid Turnover in Untreated Gestational Diabetes

OBJECTIVE Although gestational diabetes affects as many as 3% of all pregnant women, specific aspects of glucose and protein metabolism in this population have not been clearly delineated. We tested the hypothesis that gestational diabetes mellitus (GDM) results in increased glucose production and proteolysis during fasting.

RESEARCH DESIGN AND METHODS Using tracer isotope infusions, the rate of appearance (R_a) of glucose, leucine, phenylalanine and tyrosine, phenylalanine hydroxylation, leucine oxidation, and urea nitrogen excretion were determined after an overnight fast in 10 GDM subjects, within 2 weeks of diagnosis and before initiation of treatment, and in a matched control group of nine healthy nondiabetic pregnant women.

RESULTS Fasting glucose R_a was similar in GDM patients and control subjects (GDM, 12.8 ± 1.1 vs. control subjects, 12.8 ± 0.9 μumol · kg⁻¹ . min⁻¹). Leucine and phenylalanine R_a (reflecting proteolysis) also were not different between GDM patients and control subjects (GDM leucine R_a, 128 ± 14 vs. control subjects, 124 ± 5; phenylalanine R_a GDM, 35 ± 4 vs. control subjects, 40 ± 2 μumol · kg⁻¹ · h⁻¹). Furthermore, leucine oxidation and phenylalanine hydroxylation were not increased in GDM subjects, urea nitrogen excretion was actually lower in GDM patients. However, fasting insulin concentrations were significantly elevated in GDM subjects (GDM, 165 ± 35 vs. control subjects, 30 ± 5 pmol/l; P < 0.01).

CONCLUSIONS Hepatic glucose release and whole-body proteolysis in GDM patients were remarkably similar to matched pregnant control subjects. This was achieved with insulin concentrations three- to fivefold higher than normal, suggesting significant insulin resistance for both glucose and protein metabolism in GDM.