First-Trimester Dietary Phenolic Compounds and Lipids Are Associated with Hyperinsulinism at Birth in Type 1 Diabetes Pregnancy

Objective: Type 1 diabetes in pregnancy is associated with perinatal complications attributed to offspring hyperinsulinism. Conventional management prioritises glycaemia in mid/late pregnancy to reduce hyperinsulinism, but the timing and pathophysiology of hyperinsulinism remains unclear. We assessed if hyperinsulinism, quantified by cord C-peptide at birth, was associated with early pregnancy metabolism. Methods and Outcomes: 111 women in the Continuous Glucose Monitoring (CGM) in Pregnant women with Type 1 diabetes Trial (CONCEPTT) had a livebirth with measurement of cord C-peptide. Liquid chromatography-mass spectrometry of maternal serum (12, 24, 34 wks; n=101) and cord blood (n=93) measured 2105 metabolites. Statistical analysis: linear regression of Cord C-peptide and metabolites with adjustment for maternal age, BMI, parity, ethnicity, education, intervention and glycemia (and birth gestation for offspring metabolites). Significance limit was p=0.001. Results: In maternal blood at 12 weeks, positive associations were noted between nine metabolites and cord C-peptide, including lipids (monoglycerides, triglycerides and phospholipids), saccharin and three other dietary phenolic compounds. At 24 weeks, two dietary phenols and several lipids maintained positive associations. At 34 weeks, 124 species in maternal blood showed positive associations with cord C-peptide, including saccharin, free fatty acids, monoglycerides, diglycerides, triglycerides, phospholipids. The profile was distinct from that of large-for-gestational age and neonatal hypoglycemia, despite the perceived pathophysiological overlap in these conditions. In cord blood, carnitines and betonicine were associated with C-peptide. Conclusions: Lipids, saccharin and other dietary phenols in early pregnancy warrant further investigation as potentially modifiable contributors to offspring hyperinsulinism in type 1 diabetes pregnancy. Disclosure C.L.Meek: Research Support; Dexcom, Inc. Z.A.Stewart: None. D.Feig: Advisory Panel; Novo Nordisk Canada Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc. A.Koulman: None. H.R.Murphy: Advisory Panel; Medtronic, Research Support; Dexcom, Inc. Funding Diabetes UK; JDRF