Relationship between neonatal birth weight and maternal plasma amino acid profiles in lean and obese nondiabetic women and in type I diabetic pregnant women.

Profiles of hemoglobin A1c (HbA1c) and concentrations of plasma glucose and 18 plasma amino acids were obtained in ten nonobese, insulin-dependent type I diabetic women, in 9 age- and weight-matched normal women and in ten obese nondiabetic women throughout pregnancy and postpartum. In late gestation, the period of maximum fetal growth, average HbA1c, plasma glucose, and total amino acid concentrations in diabetic mothers were significantly elevated above lean control values. No differences existed between the obese and lean control groups. Lean diabetic mothers also had significantly heavier babies (mean +/- SEM) relative to the 50th percentile for gestational age and sex (119 +/- 9%) than did the lean control group (94 +/- 3%, P less than .05). Relative birth weights among control lean and obese mothers did not differ significantly (94 +/- 3% v 104 +/- 5%). Late pregnancy profiles of HbA1c and average plasma glucose did not correlate with relative weight of neonates whereas average total plasma amino acids and six individual amino acids did correlate with this parameter. These data suggest that maternal plasma amino acid concentrations may influence fetal weight generally and may have an important role in the development of fetal macrosomia in diabetic pregnancies.

Metabolic response to starvation. I. Relative effects of pregnancy and sex steroid administration in the rat.

Increased sensitivity to a fast with rapid onset of ketosis, hypoalaninemia, and hypoglycemia is characteristic of rat and human gestation. The present study examines the role of sex steroids in the development of these metabolic changes. Subgroups of female rate received 10 microgram of estradiol (E), 10 mg of progesterone (P), or the two in combination (E + P) s.c. daily for 5 days. Control rats (C) received sesame oil alone. Different groups were starved 12, 24 and 48 hr during days 4 and 5 or treatment. Plasma substrate and insulin responses were measured and compared to results of similar studies performed on rats in late gestation. Administration of E or P along had no significant effects on measured parameters as compared to control values. However, the combined E + P regimen resulted in significantly higher ketonemia, greater hypoalaninemia, and relatively higher triglyceride concentrations than in control groups during fasting. Plasma triglyceride, free fatty acid, and ketone concentrations in the pregnant group exceeded values of both the E + P and control animals. However, plasma free fatty acids in the E + P group were significantly lower as compared to control values during starvation. These data suggest that the combined effects of estradiol and progesterone enhance ketogenesis and hypoalaninemia independent of the fetal-placental unit during starvation in pregnancy. Since the ketogenic effect was associated with a relative suppression of plasma free fatty acids, this may be indicative of a direct action of these hormones on hepatic disposition of free fatty acids and/or the biosynthetic pathways for ketone body production.

Metabolic response to starvation. II. Effects of sex steroid administration to pre- and postmenopausal women.

Premenopausal women become more ketotic than do men during short term starvation. The possible influence of female sex steroids on ketosis during an 84-hr fast was studied in premenopausal women receiving combined oral contraceptive steroids. The results were compared to age and weight-matched women on no steroid birth control regimen. Although concentrations of several plasma substrates, insulin, and glucagon were measured throughout the fast, no differences between groups were observed with the exception of the 36-hr interval. At this time total plasma ketones and betahydroxybutyrate were significantly higher in women receiving oral contraceptives. In a second study six postmenopausal women were investigated in a similar fashion during a 36-hr fast. The procedure was repeated following a 5 day treatment regimen of oral estradiol and medroxyprogesterone acetate. After sex steroid treatment, total plasma ketones and betahydroxybutyrate concentrations exceeded control values significantly at 36 hr while plasma alanine and free fatty acid levels were significantly lower. The results suggest that oral estrogen-progestin combinations increase the ketogenic response of pre- and postmenopausal women during the early phases of total starvation. This hormonal effect may explain, in part, why women are more sensitive to fasting than are men.

PIP: Premenopausal women become more ketotic than do men during short-term starvation. The possible influence of female sex steroids on ketosis during an 84 hour fast was studied in premenopausal women receiving combined (OC) oral contraceptive steroids. The results were compared to age and weight-matched women on no steroid birth control regimen. Although concentrations of several plasma substrates, insulin, and glucagon were measured throughout the fast, no differences between groups were observed with the exception of the 36 hour interval. At this time total plasma ketones and betahydroxybutyrate were significantly higher in women receiving OCs. In a 2nd study, 6 postmenopausal women were investigated in a similar fashion during a 36 hour fast. The procedure was repeated following a 5-day treatment regimen of oral estradiol and medroxyprogesterone acetate. After sex steroid treatment, total plasma ketones and betahydroxybutyrate concentrations exceeded control values significantly at 36 hours while plasma alanine and free fatty acid levels were significantly lower. The results suggest that oral estrogen-progestin combinations increase the ketogenic response of pre- and postmenopausal women during the early phases of total starvation. This hormonal effect may explain, in part, why women are more sensitive to fasting than are men.