Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been suggested to differentiate hepatocyte nuclear factor 1 alpha–maturity-onset diabetes of the young (HNF1A–MODY) from type 2 diabetes (T2D). Yet, differential diagnosis of HNF1A–MODY and familial young-onset type 2 diabetes (F-YT2D) remains a difficult challenge. Thus, this study assessed the added value of hs-CRP to distinguish between the two conditions.

This prospective multicentre study included 143 HNF1A–MODY patients, 310 patients with a clinical history suggestive of HNF1A–MODY, but not confirmed genetically (F-YT2D), and 215 patients with T2D. The ability of models, including clinical characteristics and hs-CRP to predict HNF1A–MODY was analyzed, using the area of the receiver operating characteristic (AUROC) curve, and a grey zone approach was used to evaluate these models in clinical practice.

Median hs-CRP values were lower in HNF1A–MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L) patients. Clinical parameters were sufficient to differentiate HNF1A–MODY from classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A–MODY from F-YT2D were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey zone analysis, the lower boundary was set to miss<1.5% of true positives in non-tested subjects, while the upper boundary was set to perform 50% of genetic tests in individuals with no HNF1A mutation. On comparing HNF1A–MODY with F-YT2D, 65% of patients were classified in between these categories – in the zone of diagnostic uncertainty – even after adding hs-CRP to clinical parameters.

hs-CRP does not improve the differential diagnosis of HNF1A–MODY and F-YT2D.