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

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Kokko P.) > (2020-2022) > A multigenerational...

Details
MARC

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

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

Article/chapterEnglish2022

Publisher, publication year, extent ...

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

Numbers

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

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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.].

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Age at onset
Glucagon
HNF1A-MODY
Insulin deficiency
Lipolysis
Maturity-onset diabetes of the young (MODY)
MODY3
Monogenic diabetes
NEFA
Polygenic risk score for type 2 diabetes

Added entries (persons, corporate bodies, meetings, titles ...)

Rantala, ElinaHealth Care and Social Services, Vantaa (author)
Dwivedi, Om P.University of Helsinki (author)
Isomaa, BoFolkhälsan Research Center (author)
Sarelin, LeenaFolkhälsan Research Center (author)
Kokko, PaulaUniversity of Helsinki,Folkhälsan Research Center (author)
Hakaste, LiisaUniversity of Helsinki,Helsinki University Central Hospital,Folkhälsan Research Center (author)
Miettinen, Päivi J.University of Helsinki (author)
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 (author)
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 (author)
Folkhälsan Research CenterHelsinki University Central Hospital (creator_code:org_t)

Related titles

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

Internet link

Find in a library

Diabetologia (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Kettunen, Jarno ...; Rantala, Elina; Dwivedi, Om P.; Isomaa, Bo; Sarelin, Leena; Kokko, Paula; show more...; Hakaste, Liisa; Miettinen, Päivi ...; Groop, Leif C.; Tuomi, Tiinamaij ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Articles in the publication: Diabetologia

By the university: Lund University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

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.

LIBRIS.kb.se