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Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents

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Abstract

Introduction

Randomly estimated fasting hyperglycaemia in an asymptomatic individual may represent the first sign of pancreatic β-cell dysfunction.

Objective

We aimed at specifying the genetic aetiology of asymptomatic hyperglycaemia in a cohort of children and adolescents.

Subjects and methods

We analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38 males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a randomly found blood glucose level above 5.5 mmol/l. In addition to fasting glycaemia and circulating levels of insulin and C-peptide, the subjects were tested by an oral glucose tolerance test and an intravenous glucose tolerance test and screened for mutations in the genes encoding glucokinase (GCK), HNF-1α (TCF1), Kir6.2 (KCNJ11) (if aged <2 years) and HNF-4α (HNF4A) (those with a positive family history of diabetes).

Results and discussion

We identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1 mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had impaired glucose tolerance or diabetes mellitus of unknown origin. In 23 subjects, an impairment of blood glucose levels was not confirmed. We conclude that 39 of 82 paediatric patients (48%) with randomly found fasting hyperglycaemia suffered from single gene defect conditions, MODY2 being the most prevalent. An additional 11 patients (13%) progressed to overt T1DM. The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations.

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Abbreviations

FPIR:

First-phase insulin release

GCK:

Glucokinase

GCK :

Gene encoding glucokinase

HbA1C :

Glycosylated haemoglobin

HNF-1α:

Hepatocyte nuclear factor-1α

HNF4A :

Gene encoding HNF-4α

HNF-4α:

Hepatocyte nuclear factor-4α

HNF-1:

Hepatocyte nuclear factor-1

IGT/DM:

Impaired glucose tolerance/diabetes mellitus

IPF-1:

insulin promotor factor

IVGTT:

intravenous glucose tolerance test

KCNJ11 :

Gene encoding Kir6.2

Kir6.2:

Inwardly rectifying K+ channel subunit

MODY:

Maturity-onset diabetes of the young

NGT:

Normal glucose tolerance

OGTT:

Oral glucose tolerance test

PND:

Permanent neonatal diabetes mellitus

SDS:

Standard deviation score

T1DM:

Type 1 diabetes mellitus

TCF1 :

Gene encoding HNF-1α

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Acknowledgements

The study was supported by a grant of IGA MZ CR No. NB/7420-3 and by a research project of MSM 0021620814. The authors are grateful to all the referring physicians and to the families for an excellent collaboration and to Mrs. Helena Francová for the skilful assistance with metabolic tests.

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Authors and Affiliations

  1. Department of Paediatrics, 3rd Faculty of Medicine, Charles University, Vinohradska 159, 100 81, Prague 10, Czech Republic

    E. Feigerlová, Š. Pruhová, L. Dittertová & J. Lebl

  2. Department of Cellular and Molecular Biology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic

    D. Pinterová, K. Kološtová & M. Černá

  3. Steno Diabetes Centre and Hagedorn Research Institute, Gentofte, Denmark

    O. Pedersen & T. Hansen

Authors
  1. E. Feigerlová
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  2. Š. Pruhová
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  3. L. Dittertová
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  4. J. Lebl
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  5. D. Pinterová
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  6. K. Kološtová
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  7. M. Černá
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  8. O. Pedersen
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  9. T. Hansen
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Corresponding author

Correspondence to J. Lebl.

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Feigerlová, E., Pruhová, Š., Dittertová, L. et al. Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents. Eur J Pediatr 165, 446–452 (2006). https://doi.org/10.1007/s00431-006-0106-3

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  • DOI: https://doi.org/10.1007/s00431-006-0106-3

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