Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths : A Longitudinal Study
(2020) In The Journal of clinical endocrinology and metabolism 105(2).- Abstract
CONTEXT: The time-to-glucose-peak following the oral glucose tolerance test (OGTT) is a highly reproducible marker for diabetes risk. In obese youths, we lack evidence for the mechanisms underlying the effects of the TCF7L2 rs7903146 variant on glucose peak. METHODS: We analyzed the metabolic phenotype and the genotype for the TCF7L2 rs7903146 in 630 obese youths with normal (NGT) and impaired (IGT) glucose tolerance. Participants underwent a 3-hour, 9-point OGTT to estimate, using the oral minimal model, the disposition index (DI), the static (φstatic) and dynamic (φdynamic) components β-cell responsiveness and insulin sensitivity (SI). In a subgroup (n = 241) longitudinally followed for 2 years, we estimated the effect of... (More)
CONTEXT: The time-to-glucose-peak following the oral glucose tolerance test (OGTT) is a highly reproducible marker for diabetes risk. In obese youths, we lack evidence for the mechanisms underlying the effects of the TCF7L2 rs7903146 variant on glucose peak. METHODS: We analyzed the metabolic phenotype and the genotype for the TCF7L2 rs7903146 in 630 obese youths with normal (NGT) and impaired (IGT) glucose tolerance. Participants underwent a 3-hour, 9-point OGTT to estimate, using the oral minimal model, the disposition index (DI), the static (φstatic) and dynamic (φdynamic) components β-cell responsiveness and insulin sensitivity (SI). In a subgroup (n = 241) longitudinally followed for 2 years, we estimated the effect of time-to-glucose-peak on glucose tolerance change. RESULTS: Participants were grouped into early (<30 minutes) and late (≥30 minutes) glucose peakers. A delayed glucose peak was featured by a decline in φstatic (P < .001) in the absence of a difference in φdynamic. The prevalence of T-risk allele for TCF7L2 rs7903146 variant significantly increased in the late peak group. A lower DI was correlated with higher glucose concentration at 1 and 2 hours, whereas SI was inversely associated with 1-hour glucose. Glucose peak <30 minutes was protective toward worsening of glucose tolerance overtime (odds ratio 0.35 [0.15-0.82]; P = .015), with no subjects progressing to NGT or persisting IGT, in contrast to the 40% of progressor in those with late glucose peak. CONCLUSION: The prevalence of T-risk allele for the TCF7L2 rs7903146 prevailed in the late time-to-glucose peak group, which in turn is associated with impaired β-cell responsiveness to glucose (φ), thereby predisposing to prediabetes and diabetes in obese youths.
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- author
- Galderisi, Alfonso ; Tricò, Domenico ; Dalla Man, Chiara ; Santoro, Nicola ; Pierpont, Bridget ; Groop, Leif LU ; Cobelli, Claudio and Caprio, Sonia
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- pediatric obesity, prediabetes, TCF7L2, time to glucose peak
- in
- The Journal of clinical endocrinology and metabolism
- volume
- 105
- issue
- 2
- article number
- dgz207
- publisher
- Oxford University Press
- external identifiers
-
- pmid:31972003
- scopus:85078266343
- ISSN
- 1945-7197
- DOI
- 10.1210/clinem/dgz207
- language
- English
- LU publication?
- yes
- id
- b555247f-ddf2-4a39-a5af-20e8e75c383c
- date added to LUP
- 2020-02-05 08:31:21
- date last changed
- 2024-10-03 21:07:36
@article{b555247f-ddf2-4a39-a5af-20e8e75c383c,
abstract = {{<p>CONTEXT: The time-to-glucose-peak following the oral glucose tolerance test (OGTT) is a highly reproducible marker for diabetes risk. In obese youths, we lack evidence for the mechanisms underlying the effects of the TCF7L2 rs7903146 variant on glucose peak. METHODS: We analyzed the metabolic phenotype and the genotype for the TCF7L2 rs7903146 in 630 obese youths with normal (NGT) and impaired (IGT) glucose tolerance. Participants underwent a 3-hour, 9-point OGTT to estimate, using the oral minimal model, the disposition index (DI), the static (φstatic) and dynamic (φdynamic) components β-cell responsiveness and insulin sensitivity (SI). In a subgroup (n = 241) longitudinally followed for 2 years, we estimated the effect of time-to-glucose-peak on glucose tolerance change. RESULTS: Participants were grouped into early (<30 minutes) and late (≥30 minutes) glucose peakers. A delayed glucose peak was featured by a decline in φstatic (P < .001) in the absence of a difference in φdynamic. The prevalence of T-risk allele for TCF7L2 rs7903146 variant significantly increased in the late peak group. A lower DI was correlated with higher glucose concentration at 1 and 2 hours, whereas SI was inversely associated with 1-hour glucose. Glucose peak <30 minutes was protective toward worsening of glucose tolerance overtime (odds ratio 0.35 [0.15-0.82]; P = .015), with no subjects progressing to NGT or persisting IGT, in contrast to the 40% of progressor in those with late glucose peak. CONCLUSION: The prevalence of T-risk allele for the TCF7L2 rs7903146 prevailed in the late time-to-glucose peak group, which in turn is associated with impaired β-cell responsiveness to glucose (φ), thereby predisposing to prediabetes and diabetes in obese youths.</p>}},
author = {{Galderisi, Alfonso and Tricò, Domenico and Dalla Man, Chiara and Santoro, Nicola and Pierpont, Bridget and Groop, Leif and Cobelli, Claudio and Caprio, Sonia}},
issn = {{1945-7197}},
keywords = {{pediatric obesity; prediabetes; TCF7L2; time to glucose peak}},
language = {{eng}},
number = {{2}},
publisher = {{Oxford University Press}},
series = {{The Journal of clinical endocrinology and metabolism}},
title = {{Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths : A Longitudinal Study}},
url = {{http://dx.doi.org/10.1210/clinem/dgz207}},
doi = {{10.1210/clinem/dgz207}},
volume = {{105}},
year = {{2020}},
}