In patients with HNF1A-MODY (Maturity-Onset Diabetes of the Young caused by HNF1A variants) and other types of diabetes, fucosylation of alpha-1-acid glycoprotein (AGP) was analyzed and it was inferred that a glycopeptide based diagnostic tool would be useful for patient stratification by offering information regarding the functionality of HNF1A. It could aid the interpretation of DNA sequencing outcomes and serve as a valuable addition to the differential diagnostic process.

• This study included two independent cohorts: a) 466 persons with different diabetes subtypes to test the fucosylation differences, b) 98 selected individuals to test the discriminative potential for pathogenic HNF1A variants; a recently built LC-MS method for AGP N-glycopeptide analysis was utilized in both cohorts.

• Findings demonstrated significant decrease in AGP fucosylation linked with HNF1A-MODY vs other diabetes subtypes.

• In addition, significant discriminatory potential of individual fucosylated AGP glycopeptides was corroborated by ROC curve analysis, where the best performing glycopeptide yielded an AUC of 0.94 (95% CI 0.90-0.99).