Aim: To evaluate the effect of faster-acting insulin aspart (faster aspart) vs. insulin aspart (IAsp) on fetal growth and glycemic control in pregnant women with type 1 or type 2 diabetes. Methods: In a single-center, open-label trial from November 2019 to May 2022 women were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump) and randomized to faster aspart or IAsp from 8 to 13 weeks. Primary outcome was offspring birthweight standard deviation (SD) score. Secondary outcomes included mild hypoglycemia (managed by the woman) in the previous week, HbA1c at inclusion, 21, 33, and 35 weeks, and severe hypoglycemia (requiring third party assistance) reported in a structured interview. Results: In total, 216 women were included and randomized to faster aspart or IAsp (n=109 vs. n=107). Baseline data were comparable in both groups. Primary outcome data were available in 94% (71% type 1 (of which 19% on insulin pump), 29% type 2 diabetes). Offspring birthweight SD score was median 0.7 (interquartile range -0.3-2.0) vs. 1.1 (0.4-1.9), mean difference -0.2 (95% confidence interval -0.6-0.1), p=0.23 with 41% vs. 46% large for gestational age infants (p=0.39). From randomization to delivery 1 (1%) vs. 7 (7%) women reported severe hypoglycemia (p=0.07) with fewer events reported by women using faster aspart compared to IAsp (1 vs. 10 events, p=0.03). At 33 weeks, women using faster aspart reported fewer mild hypoglycemic events in the previous week compared to IAsp (2.0 (0.8 - 4.0) vs. 3.0 (1.0 - 5.0), p=0.03), while HbA1c was 41 (38-46) vs. 43 (39-46) mmol/mol, p=0.28. Prevalence of preeclampsia was 15% vs. 12% (p=0.51) and preterm delivery <37 weeks 19% vs. 22% (p=0.64). No perinatal deaths were reported. Conclusion: In pregnant women with type 1 or type 2 diabetes, use of faster aspart resulted in comparable fetal growth and HbA1c with less severe hypoglycemia compared to IAsp. Disclosure S.K.Noergaard: Research Support; Novo Nordisk A/S. E.R.Mathiesen: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk, Research Support; Medtronic, Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Novo Nordisk, Stock/Shareholder; Novo Nordisk. T.D.Clausen: None. J.Søholm: Research Support; Novo Nordisk A/S. P.Holmager: None. N.C.Do: Research Support; Novo Nordisk Foundation. P.Damm: Other Relationship; Novo Nordisk A/S. L.Ringholm: Research Support; Novo Nordisk A/S. Funding Novo Nordisk A/S (U1111-1209-6358)

Aims: Investigate glycemic control and risk of perinatal complications in women with type 1 diabetes (T1D) treated with insulin pump vs. multiple daily injections (MDI) during pregnancy. Methods: A secondary analysis of a prospective cohort of 2003 pregnant women. Odds ratios (OR) were estimated by logistic regression in crude and adjusted models for potential confounders. Results: In total, 723 women were treated with pump and 1280 were treated with MDI. At baseline (gestational weeks 8.6 (IQR: 7-10)) pump users had significant lower mean HbA1c (51.0 (10.2) mmol/mol (6.8 (0.9) %) vs. 54.2 (14.5) mmol/mol (7.1 (1.3) %), P < 0.001), longer diabetes duration (mean (SD) 18.3 (7.8) vs. 14.5 (8.3) years, p < 0.001) and higher prevalence of retinopathy (35.5% vs. 24.8%, p < 0.001). HbA1c in late pregnancy was similar (46.2 (9.4) mmol/mol (6.4 (0.9) %) vs. 46.4 (10.8) mmol/mol (6.4 (1.0) %), P=0.7458). Proportion of offspring being large for gestational age (LGA) was 59.0% (pump) vs. 52.2% (MDI) (adjusted OR 1.33 [95%CI 1.07;1.65], P=0.009) and born preterm 39.6% vs. 32.1% (adjusted OR 1.52 [95%CI 1.23;1.87], P=0.0001) (Table). No statistically significant difference was observed for other endpoints. Conclusion: Insulin pump treatment in pregnant women with T1D was associated with higher risk of LGA offspring and preterm delivery compared with MDI. Disclosure I.H.Thorius: Employee; Novo Nordisk A/S. L.N.Husemoen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. R.Baastrup nordsborg: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. A.Alibegovic: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. M.Gall: Employee; Novo Nordisk A/S. P.Damm: Other Relationship; Novo Nordisk A/S. J.Petersen: Research Support; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Vertex Pharmaceuticals Incorporated, Gilead Sciences, Inc. E.R.Mathiesen: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk.

Aim: Umbilical cord leptin is higher than expected in some babies (relative cord hyperleptinaemia) . We test the hypothesis that a higher cord leptin:fat mass ratio, putatively reflecting “leptin resistance” might be associated with adverse pregnancy outcomes. Methods: Secondary analyses from Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial a pan European study among women with a BMI ≥29 kg/m2 between 2012-14. Cord sampling and skin caliper measurements followed standardized methods. Serum cord leptin (µg/l) to fat mass ratio (kg) was classified into low, middle, and high tertiles across (where stated) and within sexes. Large/small for gestational age (SGA) used GROW. Pregnancy outcomes were compared between low and high tertiles adjusted for potential confounders using binomial logistic regression. Results: Among the 349 eligible babies (mean gestational age 39.7 ± 1.4 weeks, female 49%) the median (interquartile range) leptin-fat mass ratio (both sexes combined) was 20.2 (11.4-30.8) , top tertile (TT) was >25.3 and low tertile (LT) was <14.9 . Compared with babies in the LT group, those in the TT group had higher cord erythropoietin (30.2 (16.7-59.2) vs. 20.3 (12.4-35.6) µg/l p = 0.002, respectively, both sexes) with higher cord serum C peptide (0.7 (0.5­-1.0) vs. 0.5 (0.3-0.8) µg/l p = 0.005) , lower birthweight (3435 ± 5vs. 37± 412 gm, p = 0.002) in boys but not in girls. Cord glucose was similar. Among males, those in the TT had higher risk of SGA (25.0% vs. 8.5%; OR 3.61 (95%CI 1.21-10.76)) but lower risk of cesarean section (0.39 (0.17-0.88)) . Among females, mothers in the TT had higher rate of pregnancy induced hypertension (3.93 (1.21-12.71)) . Conclusions: Relative cord hyperleptinaemia is associated with reduced fetal growth (boys only) , and possible relative fetal hypoxia (both sexes) . Further studies are required to evaluate the implications of these findings on future metabolism. Disclosure J.Immanuel: None. D.M.Jensen: None. E.R.Mathiesen: Consultant; Novo Nordisk A/S, Speaker's Bureau; Novo Nordisk A/S. D.J.Hill: None. P.Damm: Advisory Panel; Novo Nordisk A/S. F.J.Snoek: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Roche Diabetes Care, Research Support; Novo Nordisk A/S, Sanofi, Speaker's Bureau; Insulet Corporation. J.Adelantado: None. E.Wender-ozegowska: None. D.Simmons: Other Relationship; Elsevier, Research Support; Abbott, Hitachi, Ltd., Novo Nordisk, Speaker's Bureau; Sanofi. G.Desoye: None. M.Vanpoppel: None. A.Kautzky-willer: None. R.Corcoy: None. A.Bertolotto: Research Support; AstraZeneca, Novo Nordisk, Speaker's Bureau; Abbott Diagnostics, Lilly Diabetes. F.P.Dunne: None. J.Harreiter: None. L.Andersen: None. Funding EU FP7 (242187)