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New clinical screening strategy to distinguish HNF1A variant-induced diabetes from young early-onset type 2 diabetes in a Chinese population
  1. Yumin Ma1,
  2. Siqian Gong1,
  3. Xirui Wang2,
  4. Xiaoling Cai1,
  5. Xinhua Xiao3,
  6. Weijun Gu4,
  7. Jinkui Yang5,
  8. Liyong Zhong6,
  9. Jianzhong Xiao7,
  10. Meng Li1,
  11. Wei Liu1,
  12. Simin Zhang1,
  13. Xianghai Zhou1,
  14. Yufeng Li8,
  15. Lingli Zhou1,
  16. Yu Zhu1,
  17. Yingying Luo1,
  18. Qian Ren1,
  19. Xiuting Huang1,
  20. Xueying Gao1,
  21. Xiuying Zhang1,
  22. Rui Zhang1,
  23. Ling Chen1,
  24. Fang Wang6,
  25. Qiuping Wang9,
  26. Mengdie Hu1,
  27. Xueyao Han1,
  28. Linong Ji1
  1. 1Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, China
  2. 2Department of Endocrinology and Metabolism, Beijing Airport Hospital, Beijing, China
  3. 3Department of Endocrinology, Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  4. 4Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
  5. 5Department of Endocrinology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China
  6. 6Department of Endocrinology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
  7. 7Department of Endocrinology and Metabolism, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
  8. 8Department of Endocrinology and Metabolism, Beijing Pinggu Hospital, Beijing, China
  9. 9Department of Endocrinology, Beijing Liangxiang Hospital, Capital Medical University, Beijing, China
  1. Correspondence to Dr Linong Ji; jiln{at}; Dr Xueyao Han; xueyaohan{at}


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.

  • screening strategies
  • HNF1a
  • MODY
  • type 2 diabetes

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  • YM, SG and XW contributed equally.

  • XHa and LJ contributed equally.

  • Contributors YM performed a literature review, collected data, analyzed the data, and wrote the manuscript. LJ and XH designed the study, contributed to the discussion, and reviewed and edited the manuscript. SG, XW, XC, XX, WG, JY, LZhon, JX, ML,WL, SZ, XZho, YLi, LZhou, YZ, YLu, QR, XHu, XG, XZha, RZ, LC, FW, QW and MH help collect the data and reviewed the manuscript. YM, XHa and LJ are the guarantors of this work and, as such, had full access to all the data reported in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final draft.

  • Funding 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).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was performed in accordance with the tenets of the Declaration of Helsinki and approved by the ethics committee of Peking University People’s Hospital. Written informed consent was obtained from all participants.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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