Effect of pregnancy for females born small on later life metabolic disease risk

PLoS One. 2012;7(9):e45188. doi: 10.1371/journal.pone.0045188. Epub 2012 Sep 13.

Abstract

There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. The aim of this study was to determine whether growth restricted females develop long-term impairment of metabolic control after an adverse pregnancy adaptation. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) in late pregnancy (E18) in F0 female rats. F1 Control and Restricted female offspring were mated with normal males and allowed to deliver (termed Ex-Pregnant). Age-matched Control and Restricted Virgins were also studied and glucose tolerance and insulin secretion were determined. Pancreatic morphology and hepatic glycogen and triacylglycerol content were quantified respectively. Restricted females were born lighter than Control and remained lighter at all time points studied (p<0.05). Glucose tolerance, first phase insulin secretion and liver glycogen and triacylglycerol content were not different across groups, with no changes in β-cell mass. Second phase insulin secretion was reduced in Restricted Virgins (-34%, p<0.05) compared to Control Virgins, suggestive of enhanced peripheral insulin sensitivity but this was lost after pregnancy. Growth restriction was associated with enhanced basal hepatic insulin sensitivity, which may provide compensatory benefits to prevent adverse metabolic outcomes often associated with being born small. A prior pregnancy was associated with reduced hepatic insulin sensitivity with effects more pronounced in Controls than Restricted. Our data suggests that pregnancy ameliorates the enhanced peripheral insulin sensitivity in growth restricted females and has deleterious effects for hepatic insulin sensitivity, regardless of maternal birth weight.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Animals, Newborn
  • Blood Glucose / metabolism
  • Body Weight
  • Diabetes, Gestational / metabolism*
  • Diabetes, Gestational / physiopathology
  • Female
  • Glucose Tolerance Test
  • Glycogen / metabolism
  • Humans
  • Infant, Low Birth Weight / metabolism
  • Infant, Newborn
  • Insulin / metabolism*
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Liver / metabolism
  • Male
  • Models, Biological
  • Placental Insufficiency / metabolism*
  • Placental Insufficiency / physiopathology
  • Pregnancy
  • Pregnancy, Animal*
  • Rats
  • Risk
  • Triglycerides / metabolism

Substances

  • Blood Glucose
  • Insulin
  • Triglycerides
  • Glycogen

Grants and funding

This study was supported by National March of Dimes and Heart Foundation grants to MEW and KMM. LAG was supported by a National Heart Foundation of Australia Biomedical Scholarship. KMM was supported by an National Healthy Marriage Resource Center Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.