Abstract Introduction The young-onset diabetes seen in HNF1A-MODY is often misdiagnosed as Type 2 diabetes. Type 2 diabetes, unlike HNF1A-MODY, is associated with insulin resistance and a characteristic dyslipidaemia. We aimed to compare the lipid profiles in HNF1A-MODY, Type 2 diabetes and control subjects and to determine if lipids can be used to aid the differential diagnosis of diabetes sub-type. Methods 1) 14 subjects in each group (HNF1A-MODY, Type 2 diabetes and controls) were matched for gender and BMI. Fasting lipid profiles and HDL lipid constituents were compared in the 3 groups. 2) HDL-cholesterol was assessed in a further 267 patients with HNF1A-MODY and 297 patients with a diagnosis of Type 2 diabetes to determine its discriminative value. Results 1) In HNF1A-MODY subjects, plasma-triglycerides were lower (1.36 vs. 1.93mmol/l, p=0.07) and plasma-HDL-cholesterol was higher than in subjects with Type 2 diabetes (1.47 vs. 1.15mmol/l, p=0.0008), but was similar to controls. Furthermore, in the isolated HDL; HDL-phospholipid and HDL-cholesterol ester content were higher in HNF1A-MODY, than in Type 2 diabetes (1.59 vs. 1.33mmol/L, p=0.04 and 1.10 vs. 0.83mmol/L, p=0.019, respectively), but were similar to controls (1.59 vs. 1.45mmol/L, p=0.35 and 1.10 vs. 1.21mmol/L, p=0.19, respectively). 2) A plasma-HDL-cholesterol >1.12mmol/L was 75% sensitive and 64% specific (ROC AUC=0.76) at discriminating HNF1A-MODY from Type 2 diabetes. Conclusion The plasma-lipid profiles of HNF1A-MODY and the lipid constituents of HDL are similar to non-diabetic controls. However, HDL-cholesterol was higher in HNF1A-MODY than in Type 2 diabetes and could be used as a biomarker to aid in the identification of patients with HNF1A-MODY.