Apolipoprotein M can discriminate HNF 1A‐ MODY from Type 1 diabetes

Aims Missed diagnosis of maturity‐onset diabetes of the young ( MODY ) has led to an interest in biomarkers that enable efficient prioritization of patients for definitive molecular testing. Apolipoprotein M (apoM) was suggested as a biomarker for hepatocyte nuclear factor 1 alpha ( HNF 1A)‐ MODY because of its reduced expression in Hnf1a –/– mice. However, subsequent human studies examining apoM as a biomarker have yielded conflicting results. We aimed to evaluate apoM as a biomarker for HNF 1A‐ MODY using a highly specific and sensitive ELISA . Methods ApoM concentration was measured in subjects with HNF 1A‐ MODY ( n  = 69), Type 1 diabetes ( n  = 50), Type 2 diabetes ( n  = 120) and healthy control subjects ( n  = 100). The discriminative accuracy of apoM and of the apoM/ HDL ratio for diabetes aetiology was evaluated. Results Mean (standard deviation) serum apoM concentration (μmol/l) was significantly lower for subjects with HNF 1A‐ MODY [0.86 (0.29)], than for those with Type 1 diabetes [1.37 (0.26), P  = 3.1 × 10 –18 ) and control subjects [1.34 (0.22), P  = 7.2 × 10 –19 ). There was no significant difference in apoM concentration between subjects with HNF 1A‐ MODY and Type 2 diabetes [0.89 (0.28), P  = 0.13]. The C‐statistic measure of discriminative accuracy for apoM was 0.91 for HNF 1A‐ MODY vs. Type 1 diabetes, indicating high discriminative accuracy. The apoM/ HDL ratio was significantly lower in HNF 1A‐ MODY than other study groups. However, this ratio did not perform well in discriminating HNF 1A‐ MODY from either Type 1 diabetes (C‐statistic = 0.79) or Type 2 diabetes (C‐statistic = 0.68). Conclusions We confirm an earlier report that serum apoM levels are lower in HNF 1A‐ MODY than in controls. Serum apoM provides good discrimination between HNF 1A‐ MODY and Type 1 diabetes and warrants further investigation for clinical utility in diabetes diagnostics.