Genetic Susceptibility Determines β-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76)
dc.contributor.author | Carayol, J | |
dc.contributor.author | Hosking, Joanne | |
dc.contributor.author | Pinkney, Jonathan | |
dc.contributor.author | Marquis, J | |
dc.contributor.author | Charpagne, A | |
dc.contributor.author | Metairon, S | |
dc.contributor.author | Jeffery, Alison | |
dc.contributor.author | Hager, J | |
dc.contributor.author | Martin, F-P | |
dc.date.accessioned | 2020-01-23T14:22:39Z | |
dc.date.issued | 2020-03-01 | |
dc.identifier.issn | 0149-5992 | |
dc.identifier.issn | 1935-5548 | |
dc.identifier.other | 0 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/15340 | |
dc.description | No embargo required | |
dc.description.abstract |
<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Previous studies suggested that childhood prediabetes may develop prior to obesity and be associated with relative insulin deficiency. We proposed that the insulin-deficient phenotype is genetically determined and tested this hypothesis by longitudinal modeling of insulin and glucose traits with diabetes risk genotypes in the EarlyBird cohort.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>EarlyBird is a nonintervention prospective cohort study that recruited 307 healthy U.K. children at 5 years of age and followed them throughout childhood. We genotyped 121 single nucleotide polymorphisms (SNPs) previously associated with diabetes risk, identified in the adult population. Association of SNPs with fasting insulin and glucose and HOMA indices of insulin resistance and β-cell function, available from 5 to 16 years of age, were tested. Association analysis with hormones was performed on selected SNPs.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Several candidate loci influenced the course of glycemic and insulin traits, including rs780094 (GCKR), rs4457053 (ZBED3), rs11257655 (CDC123), rs12779790 (CDC123 and CAMK1D), rs1111875 (HHEX), rs7178572 (HMG20A), rs9787485 (NRG3), and rs1535500 (KCNK16). Some of these SNPs interacted with age, the growth hormone–IGF-1 axis, and adrenal and sex steroid activity.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>The findings that genetic markers influence both elevated and average courses of glycemic traits and β-cell function in children during puberty independently of BMI are a significant step toward early identification of children at risk for diabetes. These findings build on our previous observations that pancreatic β-cell defects predate insulin resistance in the onset of prediabetes. Understanding the mechanisms of interactions among genetic factors, puberty, and weight gain would allow the development of new and earlier disease-management strategies in children.</jats:p> </jats:sec> | |
dc.format.extent | 653-660 | |
dc.format.medium | Print-Electronic | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | American Diabetes Association | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Adolescent | |
dc.subject | Blood Glucose | |
dc.subject | Child | |
dc.subject | Child Development | |
dc.subject | Child, Preschool | |
dc.subject | Cohort Studies | |
dc.subject | Diabetes Mellitus, Type 2 | |
dc.subject | Fasting | |
dc.subject | Female | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Genotype | |
dc.subject | Glucose Tolerance Test | |
dc.subject | Humans | |
dc.subject | Insulin | |
dc.subject | Insulin Resistance | |
dc.subject | Insulin-Secreting Cells | |
dc.subject | Male | |
dc.subject | Pediatric Obesity | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Prediabetic State | |
dc.subject | Prospective Studies | |
dc.subject | United Kingdom | |
dc.title | Genetic Susceptibility Determines β-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76) | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000517984600027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 3 | |
plymouth.volume | 43 | |
plymouth.publication-status | Published | |
plymouth.journal | Diabetes Care | |
dc.identifier.doi | 10.2337/dc19-0806 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA03 Allied Health Professions, Dentistry, Nursing and Pharmacy | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/FoH - Community and Primary Care | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Health and Community | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBBB | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CCT&PS | |
plymouth.organisational-group | /Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR) | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2019-11-27 | |
dc.rights.embargodate | 2020-1-25 | |
dc.identifier.eissn | 1935-5548 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.2337/dc19-0806 | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
rioxxterms.type | Journal Article/Review |