Aims: Type 1 diabetes (T1D) 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 (preeclampsia, large-for-gestational-age (LGA), neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in women with Type 1 Diabetes in pregnancy trial (CONCEPTT). Methods: 174 CONCEPTT participants gave >1 non-fasting serum sample for the biorepository at 12wks (147 women), 24wks (167 women) and 34wks (160 women) with cord blood on 93 infants. Results from metabolite analysis (ultrahigh performance liquid chromatography – mass spectrometry; Metabolon, Germany) 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. Results: Maternal CGM time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triglycerides 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 triglycerides or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24wks.
Conclusions/ interpretation: Altered lipid metabolism is a key pathophysiological feature of T1D pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in T1D.