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Diabetes Care. 2016 Nov;39(11):1879-1888. Epub 2016 Jun 6.

Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes.

Author information

1
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, U.K. m.h.shepherd@exeter.ac.uk.
2
Exeter National Institute for Health Research Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
3
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, U.K.
4
Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
5
Molecular Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
6
Exeter Test Group, Institute of Health Research, University of Exeter Medical School, Exeter, U.K.
7
Department of Paediatrics, Northern Devon Healthcare NHS Trust, Barnstaple, U.K.
8
Department of Paediatrics, Royal Cornwall Hospitals NHS Trust, Truro, U.K.
9
Department of Paediatrics, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
10
Children & Young People's Outpatient Department, Plymouth Hospitals NHS Trust, Plymouth, U.K.
11
Department of Paediatrics, South Devon Healthcare NHS Foundation Trust, Torquay, U.K.
12
Child Health, School of Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, U.K.
13
Division of Cardiovascular & Diabetes Medicine, School of Medicine, University of Dundee, Dundee, U.K.

Abstract

OBJECTIVE:

Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing.

RESEARCH DESIGN AND METHODS:

We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ≥0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes.

RESULTS:

A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients).

CONCLUSIONS:

This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.

PMID:
27271189
PMCID:
PMC5018394
DOI:
10.2337/dc16-0645
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

There are no conflicts of interest to declare.

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