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
- 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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