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Metabolic and Genet...
Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths : A Longitudinal Study
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- Galderisi, Alfonso (författare)
- University of Padova,Yale University
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- Tricò, Domenico (författare)
- Sant'Anna School of Advanced Studies
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- Dalla Man, Chiara (författare)
- University of Padova
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- Santoro, Nicola (författare)
- Yale University
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- Pierpont, Bridget (författare)
- Yale University
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- Groop, Leif (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Cobelli, Claudio (författare)
- University of Padova
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- Caprio, Sonia (författare)
- Yale University
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(creator_code:org_t)
- 2020-01-23
- 2020
- Engelska.
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:2
- Relaterad länk:
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http://dx.doi.org/10...
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
Nyckelord
- pediatric obesity
- prediabetes
- TCF7L2
- time to glucose peak
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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