Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study
Aims/hypothesis We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design. Methods We performed MR analysis using data from European genome-wide association studies of childhood adiposity, l...
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| Veröffentlicht in: | Diabetologia 2023-06, Vol.66 (6), p.1052-1056 |
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| container_title | Diabetologia |
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| creator | Wei, Yuxia Richardson, Tom G. Zhan, Yiqiang Carlsson, Sofia |
| description | Aims/hypothesis
We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design.
Methods
We performed MR analysis using data from European genome-wide association studies of childhood adiposity, latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD).
Results
Higher levels of childhood adiposity had positive genetically predicted effects on LADA (OR 1.62, 95% CI 1.05, 2.52), SIDD (OR 2.11, 95% CI 1.18, 3.80), SIRD (OR 2.76, 95% CI 1.60, 4.75) and MOD (OR 7.30, 95% CI 4.17, 12.78), but not MARD (OR 1.06, 95% CI 0.70, 1.60).
Conclusions/interpretation
Childhood adiposity is a risk factor not only for adult-onset diabetes primarily characterised by obesity or insulin resistance, but also for subtypes primarily characterised by insulin deficiency or autoimmunity. These findings emphasise the importance of preventing childhood obesity.
Graphical abstract |
| doi_str_mv | 10.1007/s00125-023-05883-x |
| format | Article |
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We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design.
Methods
We performed MR analysis using data from European genome-wide association studies of childhood adiposity, latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD).
Results
Higher levels of childhood adiposity had positive genetically predicted effects on LADA (OR 1.62, 95% CI 1.05, 2.52), SIDD (OR 2.11, 95% CI 1.18, 3.80), SIRD (OR 2.76, 95% CI 1.60, 4.75) and MOD (OR 7.30, 95% CI 4.17, 12.78), but not MARD (OR 1.06, 95% CI 0.70, 1.60).
Conclusions/interpretation
Childhood adiposity is a risk factor not only for adult-onset diabetes primarily characterised by obesity or insulin resistance, but also for subtypes primarily characterised by insulin deficiency or autoimmunity. These findings emphasise the importance of preventing childhood obesity.
Graphical abstract</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-023-05883-x</identifier><identifier>PMID: 36843089</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adipose tissue ; Adiposity - genetics ; Adult ; Age ; Autoimmune diseases ; Autoimmunity ; Child ; Childhood ; Children ; Correlation of Data ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Human Physiology ; Humans ; Insulin - genetics ; Insulin resistance ; Insulin Resistance - genetics ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Obesity ; Pediatric Obesity ; Risk factors ; Short Communication</subject><ispartof>Diabetologia, 2023-06, Vol.66 (6), p.1052-1056</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-6fa742f71f11eae0cf52bffa1c922991b63452f979862cd661b3bafbe87e01593</citedby><cites>FETCH-LOGICAL-c513t-6fa742f71f11eae0cf52bffa1c922991b63452f979862cd661b3bafbe87e01593</cites><orcidid>0000-0002-7918-2040 ; 0000-0002-3390-0844 ; 0000-0001-5815-9725 ; 0000-0002-9497-2331</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-023-05883-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-023-05883-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36843089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:152047026$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Yuxia</creatorcontrib><creatorcontrib>Richardson, Tom G.</creatorcontrib><creatorcontrib>Zhan, Yiqiang</creatorcontrib><creatorcontrib>Carlsson, Sofia</creatorcontrib><title>Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design.
Methods
We performed MR analysis using data from European genome-wide association studies of childhood adiposity, latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD).
Results
Higher levels of childhood adiposity had positive genetically predicted effects on LADA (OR 1.62, 95% CI 1.05, 2.52), SIDD (OR 2.11, 95% CI 1.18, 3.80), SIRD (OR 2.76, 95% CI 1.60, 4.75) and MOD (OR 7.30, 95% CI 4.17, 12.78), but not MARD (OR 1.06, 95% CI 0.70, 1.60).
Conclusions/interpretation
Childhood adiposity is a risk factor not only for adult-onset diabetes primarily characterised by obesity or insulin resistance, but also for subtypes primarily characterised by insulin deficiency or autoimmunity. These findings emphasise the importance of preventing childhood obesity.
Graphical abstract</description><subject>Adipose tissue</subject><subject>Adiposity - genetics</subject><subject>Adult</subject><subject>Age</subject><subject>Autoimmune diseases</subject><subject>Autoimmunity</subject><subject>Child</subject><subject>Childhood</subject><subject>Children</subject><subject>Correlation of Data</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Insulin - genetics</subject><subject>Insulin resistance</subject><subject>Insulin Resistance - genetics</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Obesity</subject><subject>Pediatric Obesity</subject><subject>Risk factors</subject><subject>Short Communication</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><recordid>eNp9kktv1DAUhSMEokPhD7BAkdiwMVw_kthsUDXiJRWxAYmd5STXMy4Ze7CdtrPmj-PpDIWyYGXL5zvH9tWpqqcUXlKA7lUCoKwhwDiBRkpOru9VCyo4IyCYvF8t9jqhsv12Uj1K6QIAeCPah9UJb6XgINWi-rlcu2lchzDWZnTbkFze1caPtQ-XONVp7vNui6kOtujzlEnwCXM9OtNjxvS6NvUn9CNOzvg6FmPYuGSyC_4mZYU-bJBcuRH3e8xuqIcQI04HJuV53D2uHlgzJXxyXE-rr-_efll-IOef339cnp2ToaE8k9aaTjDbUUspGoTBNqy31tBBMaYU7VsuGmZVp2TLhrFtac97Y3uUHQJtFD-tyCE3XeF27vU2uo2JOx2M08ej72WHWohOKF74Nwe-KBscB_Q5mumO7a7i3VqvwqWmQFsOHZSEF8eEGH7MmLIu0xlwmozHMCfNOglCUkWbgj7_B70Ic_RlHppJUKqlFESh2IEaYkgpor19DQW9L4U-lEKXUuibUujrYnr29z9uLb9bUAB-HEyR_Arjn7v_E_sLQGXG_A</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>Wei, Yuxia</creator><creator>Richardson, Tom G.</creator><creator>Zhan, Yiqiang</creator><creator>Carlsson, Sofia</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-7918-2040</orcidid><orcidid>https://orcid.org/0000-0002-3390-0844</orcidid><orcidid>https://orcid.org/0000-0001-5815-9725</orcidid><orcidid>https://orcid.org/0000-0002-9497-2331</orcidid></search><sort><creationdate>20230601</creationdate><title>Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study</title><author>Wei, Yuxia ; Richardson, Tom G. ; Zhan, Yiqiang ; Carlsson, Sofia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-6fa742f71f11eae0cf52bffa1c922991b63452f979862cd661b3bafbe87e01593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adipose tissue</topic><topic>Adiposity - genetics</topic><topic>Adult</topic><topic>Age</topic><topic>Autoimmune diseases</topic><topic>Autoimmunity</topic><topic>Child</topic><topic>Childhood</topic><topic>Children</topic><topic>Correlation of Data</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Insulin - genetics</topic><topic>Insulin resistance</topic><topic>Insulin Resistance - genetics</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Obesity</topic><topic>Pediatric Obesity</topic><topic>Risk factors</topic><topic>Short Communication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, Yuxia</creatorcontrib><creatorcontrib>Richardson, Tom G.</creatorcontrib><creatorcontrib>Zhan, Yiqiang</creatorcontrib><creatorcontrib>Carlsson, Sofia</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wei, Yuxia</au><au>Richardson, Tom G.</au><au>Zhan, Yiqiang</au><au>Carlsson, Sofia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2023-06-01</date><risdate>2023</risdate><volume>66</volume><issue>6</issue><spage>1052</spage><epage>1056</epage><pages>1052-1056</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design.
Methods
We performed MR analysis using data from European genome-wide association studies of childhood adiposity, latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD).
Results
Higher levels of childhood adiposity had positive genetically predicted effects on LADA (OR 1.62, 95% CI 1.05, 2.52), SIDD (OR 2.11, 95% CI 1.18, 3.80), SIRD (OR 2.76, 95% CI 1.60, 4.75) and MOD (OR 7.30, 95% CI 4.17, 12.78), but not MARD (OR 1.06, 95% CI 0.70, 1.60).
Conclusions/interpretation
Childhood adiposity is a risk factor not only for adult-onset diabetes primarily characterised by obesity or insulin resistance, but also for subtypes primarily characterised by insulin deficiency or autoimmunity. These findings emphasise the importance of preventing childhood obesity.
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| subjects | Adipose tissue Adiposity - genetics Adult Age Autoimmune diseases Autoimmunity Child Childhood Children Correlation of Data Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - genetics Genome-wide association studies Genome-Wide Association Study Genomes Human Physiology Humans Insulin - genetics Insulin resistance Insulin Resistance - genetics Internal Medicine Medicine Medicine & Public Health Metabolic Diseases Obesity Pediatric Obesity Risk factors Short Communication |
| title | Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study |
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