SwePub
Sök i LIBRIS databas

  Utökad sökning

onr:"swepub:oai:lup.lub.lu.se:90d7e8d1-66fa-4bd6-80ec-08f40a56d076"
 

Sökning: onr:"swepub:oai:lup.lub.lu.se:90d7e8d1-66fa-4bd6-80ec-08f40a56d076" > A multigenerational...

  • Kettunen, Jarno L.T.Folkhälsan Research Center,Helsinki University Central Hospital,University of Helsinki (författare)

A multigenerational study on phenotypic consequences of the most common causal variant of HNF1A-MODY

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • 2021-12-24
  • Springer Science and Business Media LLC,2022
  • 12 s.

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:90d7e8d1-66fa-4bd6-80ec-08f40a56d076
  • https://lup.lub.lu.se/record/90d7e8d1-66fa-4bd6-80ec-08f40a56d076URI
  • https://doi.org/10.1007/s00125-021-05631-zDOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Aims/hypothesis: Systematic studies on the phenotypic consequences of variants causal of HNF1A-MODY are rare. Our aim was to assess the phenotype of carriers of a single HNF1A variant and genetic and clinical factors affecting the clinical spectrum. Methods: We conducted a family-based multigenerational study by comparing heterozygous carriers of the HNF1A p.(Gly292fs) variant with the non-carrier relatives irrespective of diabetes status. During more than two decades, 145 carriers and 131 non-carriers from 12 families participated in the study, and 208 underwent an OGTT at least once. We assessed the polygenic risk score for type 2 diabetes, age at onset of diabetes and measures of body composition, as well as plasma glucose, serum insulin, proinsulin, C-peptide, glucagon and NEFA response during the OGTT. Results: Half of the carriers remained free of diabetes at 23 years, one-third at 33 years and 13% even at 50 years. The median age at diagnosis was 21 years (IQR 17–35). We could not identify clinical factors affecting the age at conversion; sex, BMI, insulin sensitivity or parental carrier status had no significant effect. However, for 1 SD unit increase of a polygenic risk score for type 2 diabetes, the predicted age at diagnosis decreased by 3.2 years. During the OGTT, the carriers had higher levels of plasma glucose and lower levels of serum insulin and C-peptide than the non-carriers. The carriers were also leaner than the non-carriers (by 5.0 kg, p=0.012, and by 2.1 kg/m2 units of BMI, p=2.2 × 10−4, using the first adult measurements) and, possibly as a result of insulin deficiency, demonstrated higher lipolytic activity (with medians of NEFA at fasting 621 vs 441 μmol/l, p=0.0039; at 120 min during an OGTT 117 vs 64 μmol/l, p=3.1 × 10−5). Conclusions/interpretation: The most common causal variant of HNF1A-MODY, p.(Gly292fs), presents not only with hyperglycaemia and insulin deficiency, but also with increased lipolysis and markedly lower adult BMI. Serum insulin was more discriminative than C-peptide between carriers and non-carriers. A considerable proportion of carriers develop diabetes after young adulthood. Even among individuals with a monogenic form of diabetes, polygenic risk of diabetes modifies the age at onset of diabetes. Graphical abstract: [Figure not available: see fulltext.].

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Rantala, ElinaHealth Care and Social Services, Vantaa (författare)
  • Dwivedi, Om P.University of Helsinki (författare)
  • Isomaa, BoFolkhälsan Research Center (författare)
  • Sarelin, LeenaFolkhälsan Research Center (författare)
  • Kokko, PaulaUniversity of Helsinki,Folkhälsan Research Center (författare)
  • Hakaste, LiisaUniversity of Helsinki,Helsinki University Central Hospital,Folkhälsan Research Center (författare)
  • Miettinen, Päivi J.University of Helsinki (författare)
  • Groop, Leif C.Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki(Swepub:lu)endo-lgr (författare)
  • Tuomi, TiinamaijaLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Helsinki University Central Hospital,Folkhälsan Research Center(Swepub:lu)ti8736tu (författare)
  • Folkhälsan Research CenterHelsinki University Central Hospital (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Diabetologia: Springer Science and Business Media LLC65:4, s. 632-6430012-186X1432-0428

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy