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. 2016 Nov;39(11):1879-1888.
doi: 10.2337/dc16-0645. 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

Maggie Shepherd  1   2 , Beverley Shields  3 , Suzanne Hammersley  2 , Michelle Hudson  2 , Timothy J McDonald  3   4 , Kevin Colclough  5 , Richard A Oram  3 , Bridget Knight  2 , Christopher Hyde  6 , Julian Cox  7 , Katherine Mallam  8 , Christopher Moudiotis  9 , Rebecca Smith  10 , Barbara Fraser  11 , Simon Robertson  8 , Stephen Greene  12 , Sian Ellard  3 , Ewan R Pearson  13 , Andrew T Hattersley  3 ; UNITED Team
Affiliations

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

Maggie Shepherd et al. Diabetes Care. 2016 Nov.

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.

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Conflict of interest statement

There are no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Pathway of testing
Figure 2
Figure 2
Patient progression through pathway
See this image and copyright information in PMC

References

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