Glucose replacement to euglycemia causes hypoxia, acidosis, and decreased insulin secretion in fetal sheep with intrauterine growth restriction.
Nutritional interventions for intrauterine growth restriction (IUGR) have raised concerns for fetal toxicity, the mechanisms of which are unknown. Most of these attempts did not aim to normalize fetal metabolic conditions. Therefore, we used a model of IUGR to determine whether normalization of fetal hypoglycemia for 2 wks would be tolerated and increase insulin concentrations and pancreatic beta-cell mass. IUGR fetuses received either a direct saline infusion (Sal, the control group) or a 30% dextrose infusion (Glu) to normalize glucose concentrations. Neither insulin concentrations (0.11 +/- 0.01 Glu vs. 0.10 +/- 0.01 ng/mL Sal) nor beta-cell mass (65.2 +/- 10.3 Glu vs. 74.7 +/- 18.4 mg Sal) changed. Glucose stimulated insulin secretion (GSIS) was lower in the Glu group. Glu fetuses became progressively more hypoxic: O2 content 1.4 +/- 0.5 Glu vs. 2.7 +/- 0.4 mM Sal, p < 0.05. Partial pressure of carbon dioxide (Paco2) (53.6 +/- 0.8 Glu vs. 51.6 +/- 0.8 Sal, p < 0.05) and lactate (7.74 +/- 3.82 Glu vs. 2.47 +/- 0.55 mM Sal, p < 0.0001) were greater and pH lower (7.275 +/- 0.071 Glu vs. 7.354 +/- 0.003 Sal, p < 0.01) in the Glu group. We conclude that correction of fetal hypoglycemia is not well tolerated and fails to increase insulin concentrations or beta-cell mass in IUGR fetuses.
Rozance
Paul J
PJ
Department of Pediatrics, University of Colorado Denver and Health Sciences Center, Aurora, Colorado 80045, USA. Paul.Rozance@UCHSC.edu
Limesand
Sean W
SW
Barry
James S
JS
Brown
Laura D
LD
Hay
William W
WW
D000138:Acidosis / Q000097:blood / Q000139:chemically induced*; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005317:Fetal Growth Retardation / Q000097:blood / Q000188:drug therapy*; D005865:Gestational Age; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects*; D006863:Hydrogen-Ion Concentration; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy*; D000860:Hypoxia / Q000097:blood / Q000139:chemically induced*; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008297:Male; D010100:Oxygen / Q000097:blood; D010179:Pancreas / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D010927:Placental Insufficiency / Q000097:blood / Q000188:drug therapy*; D011247:Pregnancy; D012756:Sheep; D013997:Time Factors
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D002245:Carbon Dioxide; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D010100:Oxygen