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Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies. We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort. We included 2010 participants of the Hispanic Community Health Stud...
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| Published in: | The American journal of clinical nutrition 2020-07, Vol.112 (1), p.57-65 |
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| container_title | The American journal of clinical nutrition |
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| creator | Chen, Guo-Chong Chai, Jin Choul Yu, Bing Michelotti, Gregory A Grove, Megan L Fretts, Amanda M Daviglus, Martha L Garcia-Bedoya, Olga L Thyagarajan, Bharat Schneiderman, Neil Cai, Jianwen Kaplan, Robert C Boerwinkle, Eric Qi, Qibin |
| description | Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies.
We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort.
We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18–74 y who were free of diabetes and other major chronic diseases at baseline (2008–2011). Metabolomic profiling of fasting serum was performed using a global, untargeted approach. A total of 43 sphingolipids were quantified and, considering subclasses and chemical structures of individual species, 6 sphingolipid scores were constructed. Diabetes status was assessed using standard procedures including blood tests. Multivariable survey Poisson regressions were applied to estimate RR and 95% CI of incident diabetes associated with individual sphingolipids or sphingolipid scores.
There were 224 incident cases of diabetes identified during, on average, 6 y of follow-up. After adjustment for socioeconomic and lifestyle factors, a ceramide score (RR Q4 versus Q1 = 2.40; 95% CI: 1.24, 4.65; P-trend = 0.003) and a score of sphingomyelins with fully saturated sphingoid-fatty acid pairs (RR Q4 versus Q1 = 3.15; 95% CI: 1.75, 5.67; P-trend |
| doi_str_mv | 10.1093/ajcn/nqaa114 |
| format | article |
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We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort.
We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18–74 y who were free of diabetes and other major chronic diseases at baseline (2008–2011). Metabolomic profiling of fasting serum was performed using a global, untargeted approach. A total of 43 sphingolipids were quantified and, considering subclasses and chemical structures of individual species, 6 sphingolipid scores were constructed. Diabetes status was assessed using standard procedures including blood tests. Multivariable survey Poisson regressions were applied to estimate RR and 95% CI of incident diabetes associated with individual sphingolipids or sphingolipid scores.
There were 224 incident cases of diabetes identified during, on average, 6 y of follow-up. After adjustment for socioeconomic and lifestyle factors, a ceramide score (RR Q4 versus Q1 = 2.40; 95% CI: 1.24, 4.65; P-trend = 0.003) and a score of sphingomyelins with fully saturated sphingoid-fatty acid pairs (RR Q4 versus Q1 = 3.15; 95% CI: 1.75, 5.67; P-trend <0.001) both were positively associated with risk of diabetes, whereas scores of glycosylceramides, lactosylceramides, or other unsaturated sphingomyelins (even if having an SFA base) were not associated with risk of diabetes. After additional adjustment for numerous traditional risk factors (especially triglycerides), both associations were attenuated and only the saturated-sphingomyelin score remained associated with risk of diabetes (RR Q4 versus Q1 = 1.98; 95% CI: 1.09, 3.59; P-trend = 0.031).
Our findings suggest that a cluster of saturated sphingomyelins may be associated with elevated risk of diabetes beyond traditional risk factors, which needs to be verified in other population studies. This study was registered at clinicaltrials.gov as NCT02060344.</description><identifier>ISSN: 0002-9165</identifier><identifier>EISSN: 1938-3207</identifier><identifier>DOI: 10.1093/ajcn/nqaa114</identifier><identifier>PMID: 32469399</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Ceramide ; Chronic illnesses ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus - blood ; Diabetes Mellitus - epidemiology ; Diabetes Mellitus - ethnology ; Fatty acids ; Female ; Health risk assessment ; Health risks ; Hispanic Americans ; Hispanic or Latino - statistics & numerical data ; Humans ; lipids ; Male ; Metabolomics ; Middle Aged ; Original Research Communications ; Population studies ; Prospective Studies ; Risk analysis ; Risk Factors ; Sphingolipids ; Sphingolipids - blood ; Sphingomyelin ; Triglycerides ; United States - epidemiology ; United States - ethnology ; Young Adult</subject><ispartof>The American journal of clinical nutrition, 2020-07, Vol.112 (1), p.57-65</ispartof><rights>2020 American Society for Nutrition.</rights><rights>Copyright © The Author(s) on behalf of the American Society for Nutrition 2020. 2020</rights><rights>Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.</rights><rights>Copyright American Society for Clinical Nutrition, Inc. Jul 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-dc5165f4cce7d00ca075ff3435d40c8acaee430113aff1c7c64be54aa89710193</citedby><cites>FETCH-LOGICAL-c491t-dc5165f4cce7d00ca075ff3435d40c8acaee430113aff1c7c64be54aa89710193</cites><orcidid>0000-0002-6791-8727 ; 0000-0001-6968-6985</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002916522007699$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3535,27903,27904,45759</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32469399$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Guo-Chong</creatorcontrib><creatorcontrib>Chai, Jin Choul</creatorcontrib><creatorcontrib>Yu, Bing</creatorcontrib><creatorcontrib>Michelotti, Gregory A</creatorcontrib><creatorcontrib>Grove, Megan L</creatorcontrib><creatorcontrib>Fretts, Amanda M</creatorcontrib><creatorcontrib>Daviglus, Martha L</creatorcontrib><creatorcontrib>Garcia-Bedoya, Olga L</creatorcontrib><creatorcontrib>Thyagarajan, Bharat</creatorcontrib><creatorcontrib>Schneiderman, Neil</creatorcontrib><creatorcontrib>Cai, Jianwen</creatorcontrib><creatorcontrib>Kaplan, Robert C</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Qi, Qibin</creatorcontrib><title>Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)</title><title>The American journal of clinical nutrition</title><addtitle>Am J Clin Nutr</addtitle><description>Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies.
We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort.
We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18–74 y who were free of diabetes and other major chronic diseases at baseline (2008–2011). Metabolomic profiling of fasting serum was performed using a global, untargeted approach. A total of 43 sphingolipids were quantified and, considering subclasses and chemical structures of individual species, 6 sphingolipid scores were constructed. Diabetes status was assessed using standard procedures including blood tests. Multivariable survey Poisson regressions were applied to estimate RR and 95% CI of incident diabetes associated with individual sphingolipids or sphingolipid scores.
There were 224 incident cases of diabetes identified during, on average, 6 y of follow-up. After adjustment for socioeconomic and lifestyle factors, a ceramide score (RR Q4 versus Q1 = 2.40; 95% CI: 1.24, 4.65; P-trend = 0.003) and a score of sphingomyelins with fully saturated sphingoid-fatty acid pairs (RR Q4 versus Q1 = 3.15; 95% CI: 1.75, 5.67; P-trend <0.001) both were positively associated with risk of diabetes, whereas scores of glycosylceramides, lactosylceramides, or other unsaturated sphingomyelins (even if having an SFA base) were not associated with risk of diabetes. After additional adjustment for numerous traditional risk factors (especially triglycerides), both associations were attenuated and only the saturated-sphingomyelin score remained associated with risk of diabetes (RR Q4 versus Q1 = 1.98; 95% CI: 1.09, 3.59; P-trend = 0.031).
Our findings suggest that a cluster of saturated sphingomyelins may be associated with elevated risk of diabetes beyond traditional risk factors, which needs to be verified in other population studies. This study was registered at clinicaltrials.gov as NCT02060344.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Ceramide</subject><subject>Chronic illnesses</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus - blood</subject><subject>Diabetes Mellitus - epidemiology</subject><subject>Diabetes Mellitus - ethnology</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Health risk assessment</subject><subject>Health risks</subject><subject>Hispanic Americans</subject><subject>Hispanic or Latino - statistics & numerical data</subject><subject>Humans</subject><subject>lipids</subject><subject>Male</subject><subject>Metabolomics</subject><subject>Middle Aged</subject><subject>Original Research Communications</subject><subject>Population studies</subject><subject>Prospective Studies</subject><subject>Risk analysis</subject><subject>Risk Factors</subject><subject>Sphingolipids</subject><subject>Sphingolipids - blood</subject><subject>Sphingomyelin</subject><subject>Triglycerides</subject><subject>United States - epidemiology</subject><subject>United States - ethnology</subject><subject>Young Adult</subject><issn>0002-9165</issn><issn>1938-3207</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkc1rFDEYxoModq3ePEvAgxVcN5lkvnoQyqKOsNDD2HPIJu_sZJlJpkmmsn-J_66pu1YFwUsCye953o8HoZeUvKekZiu5V3Zlb6WklD9CC1qzaskyUj5GC0JItqxpkZ-hZyHsCaEZr4qn6IxlvKhZXS_Q9xb8POIw9cbu3GAmowOWVmNjldFgI9ZGbiFCSC9Y4psWT26aBxmNs_ibiT3uza7_TW1nn2SXOPaAGxMmaY3CazeOszXxgBuQQ9K0cdaH1c8Tuw5vkp11AV8066Zdtdebt8_Rk04OAV6c7nN08-nj13Wz3Fx__rK-2iwVr2lcapWn8TquFJSaECVJmXcd4yzXnKhKKgnAGaGUya6jqlQF30LOpazqkpK0q3P04eg7zdsRtEoTezmIyZtR-oNw0oi_f6zpxc7diZJlRV6VyeD1ycC72xlCFHs3e5t6FhmnNSVV4hL17kgp70Lw0D1UoETcxyjuYxSnGBP-6s-uHuBfuSXgzRFw8_Q_q-JIQtrinQEvgjJgFWjjQUWhnfm38AevYb2k</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Chen, Guo-Chong</creator><creator>Chai, Jin Choul</creator><creator>Yu, Bing</creator><creator>Michelotti, Gregory A</creator><creator>Grove, Megan L</creator><creator>Fretts, Amanda M</creator><creator>Daviglus, Martha L</creator><creator>Garcia-Bedoya, Olga L</creator><creator>Thyagarajan, Bharat</creator><creator>Schneiderman, Neil</creator><creator>Cai, Jianwen</creator><creator>Kaplan, Robert C</creator><creator>Boerwinkle, Eric</creator><creator>Qi, Qibin</creator><general>Elsevier Inc</general><general>Oxford University Press</general><general>American Society for Clinical Nutrition, Inc</general><scope>6I.</scope><scope>AAFTH</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>7QP</scope><scope>7T7</scope><scope>7TS</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6791-8727</orcidid><orcidid>https://orcid.org/0000-0001-6968-6985</orcidid></search><sort><creationdate>20200701</creationdate><title>Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)</title><author>Chen, Guo-Chong ; Chai, Jin Choul ; Yu, Bing ; Michelotti, Gregory A ; Grove, Megan L ; Fretts, Amanda M ; Daviglus, Martha L ; Garcia-Bedoya, Olga L ; Thyagarajan, Bharat ; Schneiderman, Neil ; Cai, Jianwen ; Kaplan, Robert C ; Boerwinkle, Eric ; Qi, Qibin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-dc5165f4cce7d00ca075ff3435d40c8acaee430113aff1c7c64be54aa89710193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Ceramide</topic><topic>Chronic illnesses</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus - blood</topic><topic>Diabetes Mellitus - epidemiology</topic><topic>Diabetes Mellitus - ethnology</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Hispanic Americans</topic><topic>Hispanic or Latino - statistics & numerical data</topic><topic>Humans</topic><topic>lipids</topic><topic>Male</topic><topic>Metabolomics</topic><topic>Middle Aged</topic><topic>Original Research Communications</topic><topic>Population studies</topic><topic>Prospective Studies</topic><topic>Risk analysis</topic><topic>Risk Factors</topic><topic>Sphingolipids</topic><topic>Sphingolipids - blood</topic><topic>Sphingomyelin</topic><topic>Triglycerides</topic><topic>United States - epidemiology</topic><topic>United States - ethnology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Guo-Chong</creatorcontrib><creatorcontrib>Chai, Jin Choul</creatorcontrib><creatorcontrib>Yu, Bing</creatorcontrib><creatorcontrib>Michelotti, Gregory A</creatorcontrib><creatorcontrib>Grove, Megan L</creatorcontrib><creatorcontrib>Fretts, Amanda M</creatorcontrib><creatorcontrib>Daviglus, Martha L</creatorcontrib><creatorcontrib>Garcia-Bedoya, Olga L</creatorcontrib><creatorcontrib>Thyagarajan, Bharat</creatorcontrib><creatorcontrib>Schneiderman, Neil</creatorcontrib><creatorcontrib>Cai, Jianwen</creatorcontrib><creatorcontrib>Kaplan, Robert C</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Qi, Qibin</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of clinical nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Guo-Chong</au><au>Chai, Jin Choul</au><au>Yu, Bing</au><au>Michelotti, Gregory A</au><au>Grove, Megan L</au><au>Fretts, Amanda M</au><au>Daviglus, Martha L</au><au>Garcia-Bedoya, Olga L</au><au>Thyagarajan, Bharat</au><au>Schneiderman, Neil</au><au>Cai, Jianwen</au><au>Kaplan, Robert C</au><au>Boerwinkle, Eric</au><au>Qi, Qibin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)</atitle><jtitle>The American journal of clinical nutrition</jtitle><addtitle>Am J Clin Nutr</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>112</volume><issue>1</issue><spage>57</spage><epage>65</epage><pages>57-65</pages><issn>0002-9165</issn><eissn>1938-3207</eissn><abstract>Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies.
We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort.
We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18–74 y who were free of diabetes and other major chronic diseases at baseline (2008–2011). Metabolomic profiling of fasting serum was performed using a global, untargeted approach. A total of 43 sphingolipids were quantified and, considering subclasses and chemical structures of individual species, 6 sphingolipid scores were constructed. Diabetes status was assessed using standard procedures including blood tests. Multivariable survey Poisson regressions were applied to estimate RR and 95% CI of incident diabetes associated with individual sphingolipids or sphingolipid scores.
There were 224 incident cases of diabetes identified during, on average, 6 y of follow-up. After adjustment for socioeconomic and lifestyle factors, a ceramide score (RR Q4 versus Q1 = 2.40; 95% CI: 1.24, 4.65; P-trend = 0.003) and a score of sphingomyelins with fully saturated sphingoid-fatty acid pairs (RR Q4 versus Q1 = 3.15; 95% CI: 1.75, 5.67; P-trend <0.001) both were positively associated with risk of diabetes, whereas scores of glycosylceramides, lactosylceramides, or other unsaturated sphingomyelins (even if having an SFA base) were not associated with risk of diabetes. After additional adjustment for numerous traditional risk factors (especially triglycerides), both associations were attenuated and only the saturated-sphingomyelin score remained associated with risk of diabetes (RR Q4 versus Q1 = 1.98; 95% CI: 1.09, 3.59; P-trend = 0.031).
Our findings suggest that a cluster of saturated sphingomyelins may be associated with elevated risk of diabetes beyond traditional risk factors, which needs to be verified in other population studies. This study was registered at clinicaltrials.gov as NCT02060344.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32469399</pmid><doi>10.1093/ajcn/nqaa114</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6791-8727</orcidid><orcidid>https://orcid.org/0000-0001-6968-6985</orcidid><oa>free_for_read</oa></addata></record> |
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| source | ScienceDirect® |
| subjects | Adolescent Adult Aged Ceramide Chronic illnesses Diabetes Diabetes mellitus Diabetes Mellitus - blood Diabetes Mellitus - epidemiology Diabetes Mellitus - ethnology Fatty acids Female Health risk assessment Health risks Hispanic Americans Hispanic or Latino - statistics & numerical data Humans lipids Male Metabolomics Middle Aged Original Research Communications Population studies Prospective Studies Risk analysis Risk Factors Sphingolipids Sphingolipids - blood Sphingomyelin Triglycerides United States - epidemiology United States - ethnology Young Adult |
| title | Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) |
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