Evidence map›Paper›PMID 27913849›Full record

ArticleDiabetologia2017

Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry.

Bente B Johansson, Henrik U Irgens, Janne Molnes, Paweł Sztromwasser, Ingvild Aukrust, Petur B Juliusson, Oddmund Søvik, Shawn Levy, Torild Skrivarhaug, Geir Joner and 3 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Diabetologia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04239586 (Switching From Insulin to Sulfonylurea in Childhood and Adult Diabetes Due to Variants in the HNF1A, HNF4A, or HNF1B Genes), which is not on this map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
13.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04239586 phase4unknown statusnot on this map

Switching From Insulin to Sulfonylurea in Childhood and Adult Diabetes Due to Variants in the HNF1A, HNF4A, or HNF1B Genes

TypeinterventionalSponsorHaukeland University HospitalRan2017 to 2022Enrolled30ConditionsMaturity-Onset Diabetes of the Young, Type 3, Maturity Onset Diabetes of the Young, Type 1, Childhood Diabetes Mellitus, Insulin-dependent Diabetes MellitusArmsSulfonylurea
3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. A rare homozygousBMJ open diabetes research & care · 2024
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Bente B JohanssonK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
Henrik U IrgensK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
Janne MolnesK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
Paweł SztromwasserCenter for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Ingvild AukrustK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
Petur B JuliussonDepartment of Paediatrics, Haukeland University Hospital, Bergen, Norway.
Oddmund SøvikK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
Shawn LevyHudson Alpha Institute for Biotechnology, Huntsville, AL, USA.
Torild SkrivarhaugDivision of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Geir JonerDivision of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Anders MolvenK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
Stefan JohanssonK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
Pål R NjølstadK. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway. pal.njolstad@uib.no.
Haukeland University Hospital · NOUniversity of Bergen · NOOslo University Hospital · NOHudsonAlpha Institute for Biotechnology · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisMODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes.

methodsUsing next-generation sequencing, we screened the HNF1A, HNF4A, HNF1B, GCK and INS genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children). Variants were classified using clinical diagnostic criteria for pathogenicity ranging from class 1 (neutral) to class 5 (pathogenic).

resultsWe identified 58 rare exonic and splice variants in cases and controls. Among antibody-negative patients, 6.5% had genetic variants of classes 3-5 (vs 2.4% in controls; p = 0.002). For the stricter classification (classes 4 and 5), the corresponding number was 4.1% (vs 0.2% in controls; p = 1.6 × 10 CONCLUSIONS/

interpretationThis is the first study screening for MODY in all antibody-negative children in a nationwide population-based registry. Our results suggest that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5%. One-third of these MODY cases had not been recognised by clinicians. Since a precise diagnosis is important for treatment and genetic counselling, molecular screening of all antibody-negative children should be considered in routine diagnostics.

Indexed as

High-Throughput Nucleotide SequencingAdolescentAntibodiesApoptosis Regulatory ProteinsBasic Helix-Loop-Helix ProteinsCell Cycle ProteinsChildChild, PreschoolDiabetes Mellitus, Type 2FemaleGerminal Center KinasesHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHepatocyte Nuclear Factor 4Homeodomain ProteinsHumansABCC8 protein, humanAntibodiesApoptosis Regulatory ProteinsBasic Helix-Loop-Helix ProteinsBLK protein, humanCell Cycle ProteinsCEL protein, humanGerminal Center KinasesHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHepatocyte Nuclear Factor 4HNF1B protein, humanHNF4A protein, humanHomeodomain ProteinsKcnj11 ChannelKLF11 protein, humanLipaseNEUROD1 protein, humanPaired Box Transcription Factorspancreatic and duodenal homeobox 1 proteinPAX4 protein, humanPotassium Channels, Inwardly RectifyingProtein Serine-Threonine KinasesRepressor Proteinssrc-Family KinasesSulfonylurea ReceptorsTrans-ActivatorsAntibody-negativeChildhood-onset diabetesGenetic screeningMODYMonogenic diabetesNorwegian Childhood Diabetes RegistryPrevalenceSulfonylurea

Identifiers

PMID27913849
OpenAlexW2558165898

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.