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Heritability of model-derived parameters of beta cell secretion during intravenous and oral glucose tolerance tests: a study of twins

Lehtovirta, M; Kaprio, J; Groop, Leif LU ; Trombetta, M and Bonadonna, RC (2005) In Diabetologia 48(8). p.1604-1613
Abstract
Aims/hypothesis: The genetic architecture of model- derived parameters of beta cell function has never been assessed. Therefore, we estimated heritability (h(2)) for model- derived phenotypes of insulin secretion in twins. Methods: Thirty-three monozygotic (MZ) and 23 dizygotic (DZ) twin pairs from the Finnish Twin Cohort Study underwent OGTT (plasma glucose/C-peptide at 0, 30, 60, 90 and 120 min). A subset of the twin pairs (21 MZ/ 20 DZ) also underwent an IVGTT ( frequent sampling of plasma glucose/ insulin from 0 to 60 min) followed by a 160-min euglycaemic-hyperinsulinaemic clamp (45 mU . min(-1) . m(-2)). Mathematical modelling was applied to the IVGTT and the OGTT to assess first-phase ( readily releasable insulin [RRI]) and second-... (More)
Aims/hypothesis: The genetic architecture of model- derived parameters of beta cell function has never been assessed. Therefore, we estimated heritability (h(2)) for model- derived phenotypes of insulin secretion in twins. Methods: Thirty-three monozygotic (MZ) and 23 dizygotic (DZ) twin pairs from the Finnish Twin Cohort Study underwent OGTT (plasma glucose/C-peptide at 0, 30, 60, 90 and 120 min). A subset of the twin pairs (21 MZ/ 20 DZ) also underwent an IVGTT ( frequent sampling of plasma glucose/ insulin from 0 to 60 min) followed by a 160-min euglycaemic-hyperinsulinaemic clamp (45 mU . min(-1) . m(-2)). Mathematical modelling was applied to the IVGTT and the OGTT to assess first-phase ( readily releasable insulin [RRI]) and second- phase ( sigma) secretion ( IVGTT), and a global index of beta cell performance ( OGTT beta index). Intraclass correlation coefficients and genetic and non-genetic components for trait variances were computed to assess the h(2) of model- derived parameters. Results: The intraclass correlation coefficients in MZ twins were 0.78 for RRI, 0.67 for sigma and 0.57 for OGTT beta index. In DZ twins the correlation coefficients were 0.23, 0.32 and 0.42, respectively. Using the most parsimonious model for each trait, the h(2) - the proportion of variance accounted for by genetic factors - was 76% ( 95% CI: 53 - 88%) for RRI, 28% ( 34 - 80%) for sigma and 53% ( 26 - 72%) for OGTT beta index. Conclusions/ interpretation: Our findings demonstrate that model- derived parameters of insulin secretion have a substantial genetic component and may be used in the search for genetic determinants of beta cell function in humans. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
beta cell, C-peptide, heritability, insulin, twins, model
in
Diabetologia
volume
48
issue
8
pages
1604 - 1613
publisher
Springer Verlag
external identifiers
  • wos:000231219200024
  • pmid:15977011
  • scopus:23844492534
ISSN
1432-0428
DOI
10.1007/s00125-005-1815-2
language
English
LU publication?
yes
id
df806386-0191-4441-a6c2-701a352fff21 (old id 894465)
date added to LUP
2008-01-16 13:30:42
date last changed
2017-01-01 04:42:24
@article{df806386-0191-4441-a6c2-701a352fff21,
  abstract     = {Aims/hypothesis: The genetic architecture of model- derived parameters of beta cell function has never been assessed. Therefore, we estimated heritability (h(2)) for model- derived phenotypes of insulin secretion in twins. Methods: Thirty-three monozygotic (MZ) and 23 dizygotic (DZ) twin pairs from the Finnish Twin Cohort Study underwent OGTT (plasma glucose/C-peptide at 0, 30, 60, 90 and 120 min). A subset of the twin pairs (21 MZ/ 20 DZ) also underwent an IVGTT ( frequent sampling of plasma glucose/ insulin from 0 to 60 min) followed by a 160-min euglycaemic-hyperinsulinaemic clamp (45 mU . min(-1) . m(-2)). Mathematical modelling was applied to the IVGTT and the OGTT to assess first-phase ( readily releasable insulin [RRI]) and second- phase ( sigma) secretion ( IVGTT), and a global index of beta cell performance ( OGTT beta index). Intraclass correlation coefficients and genetic and non-genetic components for trait variances were computed to assess the h(2) of model- derived parameters. Results: The intraclass correlation coefficients in MZ twins were 0.78 for RRI, 0.67 for sigma and 0.57 for OGTT beta index. In DZ twins the correlation coefficients were 0.23, 0.32 and 0.42, respectively. Using the most parsimonious model for each trait, the h(2) - the proportion of variance accounted for by genetic factors - was 76% ( 95% CI: 53 - 88%) for RRI, 28% ( 34 - 80%) for sigma and 53% ( 26 - 72%) for OGTT beta index. Conclusions/ interpretation: Our findings demonstrate that model- derived parameters of insulin secretion have a substantial genetic component and may be used in the search for genetic determinants of beta cell function in humans.},
  author       = {Lehtovirta, M and Kaprio, J and Groop, Leif and Trombetta, M and Bonadonna, RC},
  issn         = {1432-0428},
  keyword      = {beta cell,C-peptide,heritability,insulin,twins,model},
  language     = {eng},
  number       = {8},
  pages        = {1604--1613},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Heritability of model-derived parameters of beta cell secretion during intravenous and oral glucose tolerance tests: a study of twins},
  url          = {http://dx.doi.org/10.1007/s00125-005-1815-2},
  volume       = {48},
  year         = {2005},
}