机构：[1]Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, China[2]Department of Endocrinology and Metabolism, Beijing Airport Hospital, Beijing, China[3]Department of Endocrinology, Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China[4]Department of Endocrinology, Chinese PLA General Hospital, Beijing, China[5]Department of Endocrinology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China临床科室内分泌科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[6]Department of Endocrinology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China首都医科大学附属天坛医院[7]Department of Endocrinology and Metabolism, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China[8]Department of Endocrinology and Metabolism, Beijing Pinggu Hospital, Beijing, China[9]Department of Endocrinology, Beijing Liangxiang Hospital, Capital Medical University, Beijing, China
ObjectiveMaturity-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 methodsA 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 <102pmol/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).ResultsIn 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 <28kg/m(2), hs-CRP <0.75mg/L, Fins <102pmol/L and HDL-c >1.12mmol/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.ConclusionOur HNF1A-CSS is useful for distinguishing patients with HNF1A-MODY from patients with EOD in a young Chinese population.
基金：
This research was supported by grants from the National Key Research
and Development Program (2016YFC1304901) and the Beijing Municipal
Commission of Science and Technology funds (Z141100007414002 and
D131100005313008).
第一作者机构：[1]Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Ma Yumin,Gong Siqian,Wang Xirui,et al.New clinical screening strategy to distinguish HNF1A variant-induced diabetes from young early-onset type 2 diabetes in a Chinese population[J].BMJ OPEN DIABETES RESEARCH & CARE.2020,8(1):doi:10.1136/bmjdrc-2019-000745.
APA：
Ma, Yumin,Gong, Siqian,Wang, Xirui,Cai, Xiaoling,Xiao, Xinhua...&Ji, Linong.(2020).New clinical screening strategy to distinguish HNF1A variant-induced diabetes from young early-onset type 2 diabetes in a Chinese population.BMJ OPEN DIABETES RESEARCH & CARE,8,(1)
MLA：
Ma, Yumin,et al."New clinical screening strategy to distinguish HNF1A variant-induced diabetes from young early-onset type 2 diabetes in a Chinese population".BMJ OPEN DIABETES RESEARCH & CARE 8..1(2020)
