The objective of this study was to analyse the effects of maternal hyperglycemia during the periconception period on fetal and postnatal development using a rabbit model. Diabetes was induced in adult New Zealand female does by a single intravenous alloxan injection (group D). Glycemia was maintained between 3 and 5 g L–1 with 2 daily subcutaneous insulin injections. Does from group D and contemporary controls (group C) were naturally mated 1 wk after induction of diabetes in group D animals, without superovulation, and embryos collected after sacrifice on Day 4 post-coitum. In Expt. 1, embryos from D (n = 11) and C (n = 13) groups were transferred respectively to the right and left horns of 3 female recipients, which were killed on Day 28. In Expt. 2, 17 D and 16 C females were mated naturally. 68 D and 98 C embryos were collected and transferred to 26 non-diabetic recipients (6–7 embryos per doe). 17 females were pregnant with no difference between C and D recipients. Fetal development was monitored by ultrasound. At birth, litters were equilibrated in number. 15 D and 7 C pups (from 4 D and 2 C litters) were killed at weaning (1 month of age). The remaining 13 D and 26 C pups (4 D and 7 C litters) were allocated to 1 of 2 feeding groups: control or obesogenic diet. The obesogenic diet was based on the control diet supplemented with animal fat (suet, 200%) and glucose (200%). Bodyweight, adiposity, and glucose metabolism were monitored until sacrifice at 5 months of age. Data were analysed by ANOVA using litter (fetuses), litter and sex (weaning), and litter and diet (5 months) as co-factors. Sex effects at 5 months were not analysed due to small numbers of animals. Fetal development was not different between D and C groups. Fetal, placental, and fetal organ weights did not differ at Day 28, except for brain weight, which was significantly lower in D fetuses (0.86 ± 0.1 v. 1.05 ± 0.08 g; P < 0.05). There was no difference in litter size at birth (3.3 ± 0.3 v. 3.6 ± 0.5 pups for D and C groups, respectively; P = 0.5), but birthweight was significantly increased in D offspring (211 ± 6 v. 194 ± 6 g; P < 0.05). There was no difference in weight after 14 days. At 1 month of age, adiposity, plasma insulin and leptin concentrations were not different between groups. In contrast, in male D offspring, fasting glycemia was significantly lower (1.7 ± 0.2 v. 2.1 ± 0.02 g L–1; P < 0.01), plasma insulin-like growth factor 1 was significantly increased (P < 0.05) and kidney/bodyweight ratio was significantly reduced (0.41 ± 0.03 v. 0.45 ± 0.04; P < 0.01). From 12 wk of age, bodyweight became significantly different between D and C groups and according to diet (P < 0.005), with D individuals being lighter than C individuals for each dietary group. Finally, fasting glycemia was significantly higher in the animals fed the obesogenic diet (1.35 ± 0.05 v. 1.19 ± 0.05 g L–1; P < 0.04), regardless of group. These data suggest that maternal hyperglycemia during the periconceptional period affects glucose metabolism and organ development in offspring with sexual dimorphism.
Profiles of glucose metabolism in different prediabetes phenotypes, classified by fasting glycemia, 2-hour OGTT, glycated hemoglobin, and 1-hour OGTT: An IMI DIRECT study
