Fetal glucose metabolism and oxygen consumption during sustained hypoglycemia.
The present study was conducted to determine the effects of chronic maternal hyperinsulinemia and hypoglycemia on fetal glucose metabolism and fetal growth. Umbilical glucose uptake (UGU), fetal glucose use rate (GUR), and oxidation fraction (GOxF), and fetal endogenous glucose production rate (EGPR) were measured in chronically catheterized, late gestation fetal lambs during moderate (group 2, n = 6) or marked (group 3, n = 6) maternal hypoglycemia induced by chronic maternal insulin infusion. Compared with normoglycemic controls (group 1, n = 10), group 2 moderate hypoglycemic animals had a 38.5% reduction in maternal glucose concentration (GA) with a subsequent 40.3% fall in fetal glucose concentration (Ga), 64% decrease in fetal insulin concentration (Ia), and a 28.9% decrease in UGU. Group 2 fetal GUR fell 13.1%. No significant EGPR was found in group 1 animals; group 2 had a measurable EGPR that was not statistically different from zero due to the wide range of values. In group 3 marked hypoglycemic animals GA was 57.4% lower than control, and Ga, Ia, and UGU were reduced 45.9%, 64%, and 75.7%, respectively. However, GUR fell by only 19.6% due to the appearance of significant fetal EGPR of 2.81 +/- 0.32 mg/min/kg. Fetal GUR in both group 2 and 3 animals were higher than the predicted range (mean +/- 1 SEM) compared with our model of fetal GUR response to changes in glucose and insulin concentrations. Fetal weights at autopsy were lower in groups 2 and 3 than group 1 controls at the same gestational age (P less than .05). We conclude that decreased fetal glucose availability leads to fetal hypoglycemia and hypoinsulinemia, development of fetal endogenous glucose production, and fetal growth retardation.
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
J E
JE
DiGiacomo
W W
WW
Hay
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism*; D006946:Hyperinsulinism / Q000139:chemically induced / Q000150:complications*; D007003:Hypoglycemia / Q000150:complications*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008431:Maternal-Fetal Exchange; D010101:Oxygen Consumption; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications*; D012756:Sheep; D014470:Umbilical Cord / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose