The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

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

På svenska

Author

  • Cosimo Giannini
  • Chiara Dalla Man
  • Leif Groop
  • Claudio Cobelli
  • Hongyu Zhao
  • Melissa M. Shaw
  • Elvira Duran
  • Bridget Pierpont
  • Allen E. Bale
  • Sonia Caprio
  • Nicola Santoro
Show all

Summary, in English

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.

Publishing year

2014

Language

English

Pages

475-482

Publication/Series

Diabetes Care

Volume

37

Issue

2

Document type

Journal article

Publisher

American Diabetes Association

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1935-5548