RT Journal Article SR Electronic T1 New clinical screening strategy to distinguish HNF1A variant-induced diabetes from young early-onset type 2 diabetes in a Chinese population JF BMJ Open Diabetes Research & Care JO BMJ Open Diab Res Care FD American Diabetes Association SP e000745 DO 10.1136/bmjdrc-2019-000745 VO 8 IS 1 A1 Ma, Yumin A1 Gong, Siqian A1 Wang, Xirui A1 Cai, Xiaoling A1 Xiao, Xinhua A1 Gu, Weijun A1 Yang, Jinkui A1 Zhong, Liyong A1 Xiao, Jianzhong A1 Li, Meng A1 Liu, Wei A1 Zhang, Simin A1 Zhou, Xianghai A1 Li, Yufeng A1 Zhou, Lingli A1 Zhu, Yu A1 Luo, Yingying A1 Ren, Qian A1 Huang, Xiuting A1 Gao, Xueying A1 Zhang, Xiuying A1 Zhang, Rui A1 Chen, Ling A1 Wang, Fang A1 Wang, Qiuping A1 Hu, Mengdie A1 Han, Xueyao A1 Ji, Linong YR 2020 UL http://drc.bmj.com/content/8/1/e000745.abstract AB Objective Maturity-onset diabetes of the young caused by hepatocyte nuclear factor-1 alpha (HNF1A) variants (HNF1A-MODY) is a common form of monogenetic diabetes. Although patients with HNF1A-MODY might specifically benefit from sulfonylurea treatment, available methods for screening this specific type of diabetes are not cost-effective. This study was designed to establish an optimized clinical strategy based on multiple biomarkers to distinguish patients with HNF1A-MODY from clinically diagnosed early-onset type 2 diabetes (EOD) for genetic testing in a Chinese population.Research design and methods A case–control study including 125 non-related young patients with EOD and 15 probands with HNF1A-MODY (cohort 1) was conducted to evaluate reported biomarkers for HNF1A-MODY. A cut-off for the fasting insulin (Fins) level, the 97.5 percentile of 150 healthy subjects with normal components of metabolic syndrome (cohort 2), was used to filter out individuals with obvious insulin resistance (Fins <102 pmol/L). An optimized clinical screening strategy (HNF1A-CSS) was established, and its effectiveness was assessed in another group of 410 young patients with EOD (cohort 3).Results In cohort 1, body mass index (BMI), serum high-density lipoprotein cholesterol (HDL-c) and high-sensitivity C reactive protein (hs-CRP) levels were confirmed to be useful for the differential diagnosis of HNF1A-MODY. In cohort 3, eight probands with HNF1A-MODY were identified. In cohort 3 and young relatives with HNF1A-MODY, meeting three of four criteria (BMI <28 kg/m2, hs-CRP <0.75 mg/L, Fins <102 pmol/L and HDL-c >1.12 mmol/L), the sensitivity and specificity of HNF1A-CSS were 100% and 69.3%, respectively. In the pooled analysis of all young patients, HNF1A-CSS displayed 90.5% sensitivity and 73.6% specificity for identifying patients with HNF1A-MODY among those with clinically diagnosed EOD.Conclusion Our HNF1A-CSS is useful for distinguishing patients with HNF1A-MODY from patients with EOD in a young Chinese population.