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Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes

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Abstract

Background

No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population.

Methods

Participants were 57 children and adolescents with type 1 diabetes aged 4.4–16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes.

Results

Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5 years had SID compared to none among patients aged ≥ 11 years.

Conclusions

Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.

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Funding

YJN is supported by National Key Research and Development Program of China (No. 2016YFC1305301), National Natural Science Foundation of China (No. 81570759), Research Fund of Zhejiang Major Medical and Health Science and Technology and National Ministry of Health (WKJ-ZJ-1804). JGBD was supported by a travel fellowship from the New Zealand-China Non-Communicable Diseases Research Collaboration Center.

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    Authors and Affiliations

    1. Department of Endocrinology, National Clinical Research Center for Child Health, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

      Jin-Na Yuan, Guan-Ping Dong, You-Jun Jiang, Wei Wu, Ke Huang, Xiao-Chun Chen, Yan Zheng, Bi-Hong Liu, José G. B. Derraik & Jun-Fen Fu

    2. Department of Pediatrics, Shaoxing Women and Children’s Hospital, Shaoxing, China

      Jian-Wei Zhang

    3. Liggins Institute, University of Auckland, Auckland, New Zealand

      Wayne S. Cutfield & José G. B. Derraik

    4. A Better Start—National Science Challenge, University of Auckland, Auckland, New Zealand

      Wayne S. Cutfield & José G. B. Derraik

    5. Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

      Wayne S. Cutfield & José G. B. Derraik

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    1. Jin-Na Yuan
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    Contributions

    YJN and ZJW contributed equally to this work as first authors. DJGB and FJF contributed equally to this work as senior authors. YJN conceptualized and designed the clinical study, compiled the data. ZJW, DGP, JYJ, WW, HK, CXC, ZY, and LBH carried out the clinical assessments. DJGB compiled and analysed the data. FJF conceptualized and designed the clinical study. YJN, ZJW, DJGB and FJF wrote the manuscript with critical input from CWS and DGP. All authors approved the final version of the manuscript.

    Corresponding author

    Correspondence to Jun-Fen Fu.

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    Ethical approval

    This study was approved by the Medical Ethics Committee of the Children’s Hospital, Zhejiang University School of Medicine (No. 2020-IRB-034), and informed consent was obtained from a parent and/or legal guardian of the patients. All of the reported investigations were performed in accordance with the ethical principles of the Declaration of Helsinki.

    Conflict of interest

    This was an investigator-initiated study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript. The authors have no financial or non-financial conflicts of interest to disclose that may be relevant to this work.

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    Yuan, JN., Zhang, JW., Cutfield, W.S. et al. Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes. World J Pediatr 17, 99–105 (2021). https://doi.org/10.1007/s12519-020-00382-0

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