title: Associations Between Type 2 Diabetes-Related Genetic Scores and Metabolic Traits, in Obese and Normal-Weight Youths.
abstract: Young-onset obesity is strongly associated with the early development of type 2 diabetes (T2D). Genetic risk scores (GRSs) related to T2D might help predicting the early impairment of glucose homeostasis in obese youths.
  
  
  
  Our objective was to investigate the contributions of four GRSs (associated with: T2D [GRS-T2D], beta-cell function [GRS-β], insulin resistance [GRS-IR], and body mass index) to the variation of traits derived from oral glucose tolerance test (OGTT) in obese and normal-weight children and young adults.
  
  
  
  This was a cross-sectional association study.
  
  
  
  A total of 1076 obese children/adolescents (age = 11.4 ± 2.8 years) and 1265 normal-weight young volunteers (age = 21.1 ± 4.4 years) of European ancestry were recruited from pediatric obesity clinics and general population, respectively.
  
  
  
  Standard OGTT was the intervention in this study.
  
  
  
  Associations between GRSs and OGTT-derived traits including fasting glucose and insulin, insulinogenic index, insulin sensitivity index, disposition index (DI) and associations between GRSs and pre-diabetic conditions were measured.
  
  
  
  GRS-β significantly associated with fasting glucose (β = 0.019; P = 3.5 × 10-4) and DI (β = -0.031; P = 8.9 × 10-4, last quartile 18% lower than first) in obese children, and nominally associated with fasting glucose (β = 0.009; P = 0.017) and DI (β = -0.030; P = 1.1 × 10-3, last quartile 11% lower than first) in normal-weight youths. GRS-T2D showed weaker contribution to fasting glucose and DI compared to GRS-β, in both obese and normal-weight youths. GRS associated with insulin resistance and GRS associated with body mass index did not associate with any traits. None of the GRSs associated with prediabetes, which affected only 4% of participants overall.
  
  
  
  Single nucleotide polymorphisms identified by genome-wide association studies to influence beta-cell function were associated with fasting glucose and indices of insulin secretion in youths, especially in obese children.
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Anita
authors: A
authors: Morandi
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Amélie
authors: A
authors: Bonnefond
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Stéphane
authors: S
authors: Lobbens
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Loïc
authors: L
authors: Yengo
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Emanuele
authors: E
authors: Miraglia Del Giudice
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Anna
authors: A
authors: Grandone
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Claire
authors: C
authors: Lévy-Marchal
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Jacques
authors: J
authors: Weill
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Claudio
authors: C
authors: Maffeis
authors: Pediatric Diabetes and Metabolic Disorders Unit (A.M. C.M.), University Hospital of Verona, Verona, Italy; University of Lille (A.B., S.L., L.Y., P.F.), CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France; Department of Woman, Child and General and Specialized Surgery (E.M.d.G., A.G.), Second University of Naples, Naples, Italy; Inserm CIE 05 - Department of Clinical Epidemiology (C.L.-M.), Robert Debré Hospital, Paris, France; Pediatric Endocrine Unit (J.W.), Lille University Hospital, Lille, France; Department of Genomics of Common Disease (P.F.), School of Public Health, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Philippe
authors: P
authors: Froguel
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000145:classification*; D055106:Genome-Wide Association Study; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007558:Italy / Q000453:epidemiology; D008297:Male; D063766:Pediatric Obesity / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment / Q000145:classification; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin