Associations between type 2 diabetes-related genetic scores and metabolic traits, in obese and normal-weight youths

Morandi, Anita, Bonnefond, Amelie, Lobbens, Stephane, Yengo, Loic, del Giudice, Emanuele Miraglia, Grandone, Anna, Levy-Marchal, Claire, Weill, Jacques, Maffeis, Claudio and Froguel, Philippe (2016) Associations between type 2 diabetes-related genetic scores and metabolic traits, in obese and normal-weight youths. Journal of Clinical Endocrinology and Metabolism, 101 11: 4244-4250. doi:10.1210/jc.2016-2432

Author Morandi, Anita
Bonnefond, Amelie
Lobbens, Stephane
Yengo, Loic
del Giudice, Emanuele Miraglia
Grandone, Anna
Levy-Marchal, Claire
Weill, Jacques
Maffeis, Claudio
Froguel, Philippe
Title Associations between type 2 diabetes-related genetic scores and metabolic traits, in obese and normal-weight youths
Journal name Journal of Clinical Endocrinology and Metabolism   Check publisher's open access policy
ISSN 1945-7197
Publication date 2016-11-01
Year available 2016
Sub-type Article (original research)
DOI 10.1210/jc.2016-2432
Open Access Status Not yet assessed
Volume 101
Issue 11
Start page 4244
End page 4250
Total pages 7
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Formatted abstract
Context: 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.

Objective: 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.

Design: This was a cross-sectional association study.

Patients: A total of 1076 obese children/adolescents (age = 11.4 ± 2.8 years) and 1265 normalweight young volunteers (age = 21.1 ± 4.4 years) of European ancestry were recruited from pediatric obesity clinics and general population, respectively.

Intervention: Standard OGTT was the intervention in this study.

Main Outcome Measures: 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.

Results: 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.

Conclusion: 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.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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