Objective: To investigate whether maternal serum pregnancy associated plasma protein-A (PAPP-A), total β human chorionic gonadotropin (hCG) levels and nuchal translucency (NT) measurements differ in women with pre-gestational diabetes mellitus (PGDM) compared to non-diabetic controls and to assess whether correction factors are needed for diabetic women in calculation of aneuploidy risks. Study Design: We performed a retrospective study of all women who underwent first trimester aneuploidy screening (11 + 0 to 13 + 6 weeks) from 2005 to 2011. The primary study outcome was the difference in PAPP-A, β-hCG and NT multiples of median between women with PGDM and non-diabetic women. Results: Of 6741 eligible patients, 103 patients with PGDM were using insulin and 4 patients were using oral hypoglycemic agents; the latter were excluded due to small number. There was 12% reduction of median PAPP-A (p = 0.001) and 18% reduction of median hCG (p = 0.006) in women with PGDM receiving insulin. There was no difference in NT. Conclusions: In women with PGDM receiving insulin, PAPP-A and β-hCG levels are significantly lower compared to non-diabetic women. This suggests that when calculating risks for aneuploidy, correction factors should be considered to adjust PAPP-A and β-hCG concentrations to those seen in non-diabetic women.