Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes

Aims/hypothesisType 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT).MethodsA total of 174 CONCEPTT participants gave & GE;1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables.ResultsMaternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks.Conclusions/interpretationAltered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes.

Automated summary

This study found that maternal hyperglycemia and offspring hyperinsulinism in women with type 1 diabetes during pregnancy are associated with perinatal complications and suboptimal pregnancy outcomes. Metabolomic analysis revealed distinct metabolite profiles for different complications, such as increased carnitines and lipid metabolites in large for gestational age infants, and changes in triacylglycerols or dietary phenols in neonatal hypoglycemia and offspring hyperinsulinism. Altered lipid metabolism is a key feature in type 1 diabetes pregnancy, suggesting the need for new strategies to optimize maternal diet and insulin dosing from the first trimester.