التفاصيل البيبلوغرافية
| العنوان: |
A multigenerational study on phenotypic consequences of the most common causal variant of HNF1A-MODY |
| المؤلفون: |
Kettunen, Jarno L. T., Rantala, Elina, Dwivedi, Om P., Isomaa, Bo, Sarelin, Leena, Kokko, Paula, Hakaste, Liisa, Miettinen, Päivi J., Groop, Leif C., Tuomi, Tiinamaija |
| المساهمون: |
Foundation for Life and Health in Finland, Nordic Network of Excellence in Disease Genetics, Jalmari ja Rauha Ahokkaan Säätiö, Novonordisk foundation, Academy of Finland, Novo Nordisk Fonden, Paavo Nurmen Säätiö, Signe ja Ane Gyllenbergin Säätiö, Perklén foundation, Närpes Health Care Foundation, Diabetesliitto, Samfundet Folkhälsan, Helsingin Yliopisto, European Commission, Ollqvist Foundation, Svenska Kulturfonden, Sigrid Juséliuksen Säätiö |
| المصدر: |
Diabetologia ; volume 65, issue 4, page 632-643 ; ISSN 0012-186X 1432-0428 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2021 |
| مصطلحات موضوعية: |
Endocrinology, Diabetes and Metabolism, Internal Medicine |
| الوصف: |
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/m 2 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 ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1007/s00125-021-05631-z |
| DOI: |
10.1007/s00125-021-05631-z.pdf |
| DOI: |
10.1007/s00125-021-05631-z/fulltext.html |
| الإتاحة: |
https://doi.org/10.1007/s00125-021-05631-zTest |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: |
edsbas.6A1F8354 |
| قاعدة البيانات: |
BASE |
