Traditional clinical criteria outperform high-sensitivity C-reactive protein for the screening of hepatic nuclear factor 1 alpha maturity-onset diabetes of the young among young Asians with diabetes

摘要

Young adults with diabetes in Asia represent a heterogeneous group. Using traditional clinical criteria to preselect individuals for testing for maturity-onset diabetes of the young (MODY) may exclude a large proportion from testing. High-sensitivity C-reactive protein (hs-CRP) has shown promise as a biomarker to differentiate hepatic nuclear factor 1 alpha (HNF1A)-MODY from type 2 diabetes. We aimed to compare the use of hs-CRP as a biomarker versus traditional criteria, to guide testing for HNF1A-MODY among a cohort of young adults with diabetes in Singapore. A total of 252 adults (age of onset ?45 years) and 20 children with diabetes were recruited. Using traditional criteria (family history of diabetes and onset of diabetes ?25 years) and an hs-CRP cut off of ?0.5 mg/l, 125 and 37 adults, respectively, were identified for HNF1A gene testing. All children underwent HNF1A gene testing. Five adults (5/143, 3.5%) with HNF1A-MODY were identified. There were no HNF1A gene mutations among the children. Traditional criteria correctly identified all five HNF1A-MODY individuals (5/125, 4%), while applying an hs-CRP level of ?0.5 mg/l selected just 1 of these 5 for HNF1A gene testing (1/37, 2.7%). None of those with a positive GAD antibody or undetectable C-peptide level had HNF1A-MODY. The use of hs-CRP to guide screening for HNF1A-MODY among Asian young adults with diabetes did not improve the diagnostic yield. Applying a combination of age of onset of diabetes under 25 years and a family history of diabetes alone could guide targeted HNF1A-MODY screening in Asians, with an expected yield of 4% diagnosed with HNF1A-MODY among those screened.