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Co-occurrence of Risk Alleles in or Near Genes Modulating Insulin Secretion Predisposes Obese Youth to Prediabetes

Giannini, Cosimo; Dalla Man, Chiara; Groop, Leif LU ; Cobelli, Claudio; Zhao, Hongyu; Shaw, Melissa M.; Duran, Elvira; Pierpont, Bridget; Bale, Allen E. and Caprio, Sonia, et al. (2014) In Diabetes Care 37(2). p.475-482
Abstract
OBJECTIVEParalleling the rise of pediatric obesity, the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) is increasing among youth. In this study, we asked whether the co-occurrence of risk alleles in or near five genes modulating insulin secretion (TCF7L2 rs7903146, IGF2BP2 rs4402960, CDKAL1 rs7754840, HHEX rs1111875, and HNF1A rs1169288) is associated with a higher risk of IGT/T2D in obese children and adolescents.RESEARCH DESIGN AND METHODSWe studied 714 obese subjects (290 boys and 424 girls; mean age 13.6 3.1 years; mean z score BMI 2.2 0.4) and evaluated the insulin secretion by using the oral minimal model and, in a subgroup of 37 subjects, the hyperglycemic clamp. Also, 203 subjects were followed up for a... (More)
OBJECTIVEParalleling the rise of pediatric obesity, the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) is increasing among youth. In this study, we asked whether the co-occurrence of risk alleles in or near five genes modulating insulin secretion (TCF7L2 rs7903146, IGF2BP2 rs4402960, CDKAL1 rs7754840, HHEX rs1111875, and HNF1A rs1169288) is associated with a higher risk of IGT/T2D in obese children and adolescents.RESEARCH DESIGN AND METHODSWe studied 714 obese subjects (290 boys and 424 girls; mean age 13.6 3.1 years; mean z score BMI 2.2 0.4) and evaluated the insulin secretion by using the oral minimal model and, in a subgroup of 37 subjects, the hyperglycemic clamp. Also, 203 subjects were followed up for a mean of 2.1 years.RESULTSWe observed that the increase of risk alleles was associated with a progressive worsening of insulin secretion (P < 0.001) mainly due to an impairment of the dynamic phase of insulin secretion (P = 0.004); the higher the number of the risk alleles, the higher the chance of progression from normal glucose tolerance (NGT) to IGT/T2D (P = 0.022). Also, for those who were IGT at baseline, a higher risk score was associated with a lower odds to revert to NGT (P = 0.026).CONCLUSIONSObese children and adolescents developing IGT/T2D have a higher genetic predisposition than those who do not show these diseases, and this predisposition is mainly related to gene variants modulating the early phase of insulin secretion. Although these data are very interesting, they need to be replicated in other cohorts. (Less)
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Contribution to journal
publication status
published
subject
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Diabetes Care
volume
37
issue
2
pages
475 - 482
publisher
American Diabetes Association
external identifiers
  • wos:000331072800036
  • scopus:84893076148
ISSN
1935-5548
DOI
10.2337/dc13-1458
language
English
LU publication?
yes
id
1d7769b2-fac3-41cb-afa2-35b52f30907a (old id 4368311)
date added to LUP
2014-04-07 09:20:37
date last changed
2017-10-29 03:51:38
@article{1d7769b2-fac3-41cb-afa2-35b52f30907a,
  abstract     = {OBJECTIVEParalleling the rise of pediatric obesity, the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) is increasing among youth. In this study, we asked whether the co-occurrence of risk alleles in or near five genes modulating insulin secretion (TCF7L2 rs7903146, IGF2BP2 rs4402960, CDKAL1 rs7754840, HHEX rs1111875, and HNF1A rs1169288) is associated with a higher risk of IGT/T2D in obese children and adolescents.RESEARCH DESIGN AND METHODSWe studied 714 obese subjects (290 boys and 424 girls; mean age 13.6 3.1 years; mean z score BMI 2.2 0.4) and evaluated the insulin secretion by using the oral minimal model and, in a subgroup of 37 subjects, the hyperglycemic clamp. Also, 203 subjects were followed up for a mean of 2.1 years.RESULTSWe observed that the increase of risk alleles was associated with a progressive worsening of insulin secretion (P &lt; 0.001) mainly due to an impairment of the dynamic phase of insulin secretion (P = 0.004); the higher the number of the risk alleles, the higher the chance of progression from normal glucose tolerance (NGT) to IGT/T2D (P = 0.022). Also, for those who were IGT at baseline, a higher risk score was associated with a lower odds to revert to NGT (P = 0.026).CONCLUSIONSObese children and adolescents developing IGT/T2D have a higher genetic predisposition than those who do not show these diseases, and this predisposition is mainly related to gene variants modulating the early phase of insulin secretion. Although these data are very interesting, they need to be replicated in other cohorts.},
  author       = {Giannini, Cosimo and Dalla Man, Chiara and Groop, Leif and Cobelli, Claudio and Zhao, Hongyu and Shaw, Melissa M. and Duran, Elvira and Pierpont, Bridget and Bale, Allen E. and Caprio, Sonia and Santoro, Nicola},
  issn         = {1935-5548},
  language     = {eng},
  number       = {2},
  pages        = {475--482},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Co-occurrence of Risk Alleles in or Near Genes Modulating Insulin Secretion Predisposes Obese Youth to Prediabetes},
  url          = {http://dx.doi.org/10.2337/dc13-1458},
  volume       = {37},
  year         = {2014},
}