dc.contributor.author | Shepherd, M | |
dc.contributor.author | Shields, B | |
dc.contributor.author | Hammersley, S | |
dc.contributor.author | Hudson, M | |
dc.contributor.author | McDonald, TJ | |
dc.contributor.author | Colclough, K | |
dc.contributor.author | Oram, RA | |
dc.contributor.author | Knight, B | |
dc.contributor.author | Hyde, C | |
dc.contributor.author | Cox, J | |
dc.contributor.author | Mallam, K | |
dc.contributor.author | Moudiotis, C | |
dc.contributor.author | Smith, R | |
dc.contributor.author | Fraser, B | |
dc.contributor.author | Robertson, S | |
dc.contributor.author | Greene, S | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | Pearson, ER | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | UNITED Team | |
dc.date.accessioned | 2016-07-04T10:56:00Z | |
dc.date.issued | 2016-06-06 | |
dc.description.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. | en_GB |
dc.description.sponsorship | This work presents independent research
commissioned by the Health Innovation
Challenge Fund, a parallel funding partnership
between the Wellcome Trust and the Department
of Health (grant HICF-1009-041); and was
supported by the National Institute for Health
Research (NIHR) Exeter Clinical Research Facility
and the South West Peninsula Diabetes Research
Network. M.S. is supported by the NIHR Exeter
Clinical Research Facility. T.J.M. is funded by an
NIHR CSO Fellowship. S.E. and A.T.H. are both
Wellcome Trust Senior Investigators. E.R.P. is a
Wellcome Trust New Investigator. A.T.H. is an
NIHR Senior Investigator. | en_GB |
dc.identifier.citation | Diabetes Care 2016 Jun; dc160645. http://dx.doi.org/10.2337/dc16-0645 | en_GB |
dc.identifier.doi | 10.2337/dc16-0645 | |
dc.identifier.other | dc16-0645 | |
dc.identifier.uri | http://hdl.handle.net/10871/22372 | |
dc.language.iso | en | en_GB |
dc.publisher | American Diabetes Association | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/27271189 | en_GB |
dc.title | Systematic population screening, using biomarkers and genetic testing, identifies 2.5% of the U.K. pediatric diabetes population with monogenic diabetes. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-07-04T10:56:00Z | |
dc.description | This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record. | en_GB |
dc.identifier.journal | Diabetes Care | en_GB |
dc.identifier.pmid | 27271189 | |