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Higher C-peptide levels and glucose requirements may identify neonates with transient hyperinsulinism hypoglycemia who will benefit from diazoxide treatment

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Abstract

The aim of the study was to characterize factors that may serve as clinical tools to identify neonates with transient neonatal hyperinsulinism hypoglycemia (HH) who may benefit from diazoxide treatment. This retrospective study included 141 neonates with transient HH (93 males) of whom 34 (24%) were treated with diazoxide. Diazoxide treatment was started at median age of 13 days (range 5–35) and discontinued at median age of 42 days (range 14–224). The maximal dose was 7.1 ± 2.3 mg/kg/day. Diazoxide-treated neonates required a higher glucose infusion rate (GIR) compared with non-treated neonates (16.6 ± 3.4 vs. 10.4 ± 4.0 mg/kg/min, respectively, P < .01), had a longer duration of intravenous fluids (15.9 ± 9.3 vs. 7.8 ± 6.5 days, P < .01), a longer hospitalization (32.8 ± 22.7 vs. 20.4 ± 13.4 days, P < .01), a longer duration of carbohydrate supplementation (38.9 ± 40.4 vs. 17.8 ± 21.4 days, P < .01), and higher mean C-peptide levels on “critical sample” (1.4 ± 0.9 vs. 0.8 ± 0.5 ng/ml, P < .01). Their insulin levels also tended to be higher (3.5 ± 2.9 vs. 2.2 ± 3.8 μU/ml, P = .07). A stepwise logistic regression model revealed that significant predictors of prolonged HH were maximal GIRs (odds ratio (OR) 1.56, 95%; confidence interval (CI) 1.3–1.88, P < .001) and C-peptide levels (OR 3.57, 95%; CI 1.3–12.1, P = .005).

Conclusion: Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.

What is Known:

• Neonates with transient hyperinsulinism usually do not require treatment beyond glucose supplementation due to its self-limited clinical course, but some may benefit from diazoxide treatment.

What is New:

• Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.

• The incidence of prolonged neonatal HH is higher than the currently accepted figures.

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Abbreviations

CI:

Confidence interval

GDM:

Gestational diabetes mellitus

GIR:

Glucose infusion rate

HH:

Hyperinsulinism hypoglycemia

IV:

Intravenous

KATP :

ATP-sensitive potassium

LGA:

Large-for-gestational-age

OR:

Odds ratio

PH:

Pulmonary hypertension

SGA:

Small-for-gestational-age

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Acknowledgments

We thank Pearl Lilos for the statistical analysis and Esther Eshkol for professional English editing.

Author information

Authors and Affiliations

  1. Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Anita Schachter Davidov, Erella Elkon-Tamir, Naomi Weintrob, Asaf Oren, Yael Lebenthal & Ori Eyal

  2. Department of Neonatology, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Alon Haham & Dror Mandel

  3. Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, , Tel Aviv, Israel

    Gabi Shefer

  4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Anita Schachter Davidov, Erella Elkon-Tamir, Alon Haham, Gabi Shefer, Naomi Weintrob, Asaf Oren, Yael Lebenthal, Dror Mandel & Ori Eyal

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  1. Anita Schachter Davidov
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Contributions

ASD and OE: Study design, literature search, data analysis and interpretation, and writing the manuscript

EET: Data collection and analysis, and literature search

YL and DM: Data collection and study design

AH, GS, NW, and AO: Data collection

All authors were involved in the preparation of the manuscript, critically reviewed the manuscript, and approved the final manuscript as submitted.

Corresponding author

Correspondence to Ori Eyal.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

The study was approved by the medical ethics committee of the Tel Aviv Sourasky Medical Center; the requirement for informed consent was waived.

Additional information

Communicated by Peter de Winter

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Davidov, A.S., Elkon-Tamir, E., Haham, A. et al. Higher C-peptide levels and glucose requirements may identify neonates with transient hyperinsulinism hypoglycemia who will benefit from diazoxide treatment. Eur J Pediatr 179, 597–602 (2020). https://doi.org/10.1007/s00431-019-03544-z

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