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GLP-1 Levels Lower in Those Exposed to Diabetes in Utero

Adult offspring of mothers who had GDM or type 1 diabetes during pregnancy showed lower levels of fasting GLP-1 and weakened glucagon suppression…

Louise Kepstrup, MD, of Copenhagen University Hospital in Denmark, and colleagues in the follow-up study, evaluated data on adult children (aged 18-27 years) from all pregnancies complicated by diet-treated gestational diabetes (n = 163) or type 1 diabetes (n = 146) between 1978 and 1985 at the Center for Pregnant Women with Diabetes in Denmark. The study also included two control groups: one consisting of 133 adult children of mothers with gestational diabetes risk factors but with normal glycemia during pregnancy and one group consisting of 125 adult children of mothers from a background population with no known risk factors for diabetes.

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All participants underwent a 75-g oral glucose tolerance test (OGTT) with blood samples drawn at 0, 30 and 120 minutes. Anthropometric measurements were also taken, and participants completed a questionnaire addressing their health, medication, diet, levels of activity and socioeconomic information. The study’s primary outcomes were glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon levels at 0, 30 and 120 minutes.

The researchers found that participants in the two diabetes-exposed groups had lower fasting plasma levels of GLP-1 compared with the participants with no known diabetes risk factors (gestational diabetes, P = .4; type 1 diabetes, P = .008). No significant differences in GIP were noted among the four groups. An association was observed between increasing blood glucose during OGTT in pregnancy and decreased post-meal glucagon suppression in the participants. Participants who were overweight or who had prediabetes or type 2 diabetes at follow-up had lower levels of GLP-1 and higher levels of glucagon regardless of prenatal exposure status.

“Lower levels of fasting GLP-1 and impaired glucagon suppression in adult offspring exposed to maternal diabetes during pregnancy are diabetogenic traits, and may contribute to glucose intolerance,” the researchers wrote. “However, further studies of the clinical implications and basal pathogenic mechanisms are needed to investigate the incretin function in offspring exposed to intrauterine hyperglycemia, and to evaluate whether the findings can be attributed to an effect of fetal programming.”

Practice Pearls:

  • Among adults who were exposed to diabetes in utero, lower levels of fasting GLP-1 and impaired glucagon suppression appear to be associated with the development of diabetes.
  • The researchers found that participants in the two diabetes-exposed groups had lower fasting plasma levels of GLP-1 compared with the participants with no known diabetes risk factors.
  • Lower levels of fasting GLP-1 and impaired glucagon suppression in adult offspring exposed to maternal diabetes during pregnancy are diabetogenic traits, and may contribute to glucose intolerance.

Kelstrup L, et al. J Clin Endocrinol Metab. 2015;doi:10.1210/jc.2014-3978.