{"doi":"10.2337/db24-0329","title":"Proteomic Signature of BMI and Risk of Type 2 Diabetes","abstract":"<jats:p>The obesity diagnosis by BMI exhibits considerable interindividual heterogeneity in metabolic phenotypes and risk of developing type 2 diabetes (T2D). We investigated the association of the proteomic signature of BMI and T2D and examined whether the proteomic signature of BMI improves the prediction of T2D risk. This study included 41,427 adults in the UK Biobank who were free of T2D at baseline and had complete data on proteomics metrics assessed by the antibody-based Olink assay. The main exposure was a proteomic BMI (pro-BMI) score calculated from 67 preidentified plasma proteins associated with BMI. During a median follow-up of 13.7 years, 2,030 incident events of T2D were documented. We observed that a higher pro-BMI score was significantly associated with a higher risk of T2D independent of actual BMI, waist-to-hip ratio, and polygenic risk score for BMI (hazard ratio comparing the highest with the lowest quartiles was 3.81; 95% CI 3.08–4.71). The pro-BMI score significantly increased the C index when added to a reference model with age, sex, and BMI (C index change, 0.023; 95% CI 0.018–0.027). The proteomic signature of BMI is significantly associated with the risk of T2D independent of BMI, waist-to-hip ratio, and genetic susceptibility to obesity. When added to the actual BMI, the proteomic signature of BMI provides significant but modest improvement in discrimination.</jats:p>\n               <jats:sec>\n                  <jats:title>Article Highlights</jats:title>\n               </jats:sec>","journal":"Diabetes","year":2025,"id":635253,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":53345,"name":"Hao Ma","orcid":"0000-0001-8585-6665","position":1,"is_corresponding":false},{"id":977687,"name":"Minghao Kou","orcid":"0000-0002-3885-4103","position":2,"is_corresponding":false},{"id":256514,"name":"Yoriko Heianza","orcid":"0000-0002-0957-9309","position":3,"is_corresponding":false},{"id":19503,"name":"Vivian Fonseca","orcid":"0000-0002-3381-7151","position":4,"is_corresponding":false},{"id":21926,"name":"Lu Qi","orcid":"0000-0002-8041-7791","position":5,"is_corresponding":false},{"id":913350,"name":"Xuan Wang","orcid":"0000-0002-6588-2951","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Proteomic Signature of BMI and Risk of Type 2 Diabetes","abstract":"<jats:p>The obesity diagnosis by BMI exhibits considerable interindividual heterogeneity in metabolic phenotypes and risk of developing type 2 diabetes (T2D). We investigated the association of the proteomic signature of BMI and T2D and examined whether the proteomic signature of BMI improves the prediction of T2D risk. This study included 41,427 adults in the UK Biobank who were free of T2D at baseline and had complete data on proteomics metrics assessed by the antibody-based Olink assay. The main exposure was a proteomic BMI (pro-BMI) score calculated from 67 preidentified plasma proteins associated with BMI. During a median follow-up of 13.7 years, 2,030 incident events of T2D were documented. We observed that a higher pro-BMI score was significantly associated with a higher risk of T2D independent of actual BMI, waist-to-hip ratio, and polygenic risk score for BMI (hazard ratio comparing the highest with the lowest quartiles was 3.81; 95% CI 3.08–4.71). The pro-BMI score significantly increased the C index when added to a reference model with age, sex, and BMI (C index change, 0.023; 95% CI 0.018–0.027). The proteomic signature of BMI is significantly associated with the risk of T2D independent of BMI, waist-to-hip ratio, and genetic susceptibility to obesity. When added to the actual BMI, the proteomic signature of BMI provides significant but modest improvement in discrimination.</jats:p>\n               <jats:sec>\n                  <jats:title>Article Highlights</jats:title>\n               </jats:sec>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39561322","pmcid":"PMC11755684","openalex_id":"https://openalex.org/W4404517864","authors":[],"funders":[{"funder_name":"National Institute of Diabetes and Digestive and Kidney Diseases","grant_id":"DK115679, DK091718, DK100383, DK078616","title":null},{"funder_name":"National Heart, Lung, and Blood Institute","grant_id":"HL071981, HL034594, HL126024","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"UM1 DK078616","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK078616","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK115679","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK078616","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK072476","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK100383","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL034594","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R21 HL126024","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"P20 GM109036","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL071981","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK091718","title":null},{"funder_name":"FIC NIH HHS","grant_id":"R21 TW010790","title":null}],"total_grants":14,"fwci":1.6971,"citation_percentile":0.85757384,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"hybrid","license":"other-oa","oa_locations":[{"url":"https://diabetesjournals.org/diabetes/article-pdf/doi/10.2337/db24-0329/789781/db240329.pdf","host_type":"journal"},{"url":"https://diabetesjournals.org/diabetes/article-pdf/doi/10.2337/db24-0329/789781/db240329.pdf","host_type":"publisher"},{"url":"https://diabetesjournals.org/diabetes/article-pdf/74/2/234/789781/db240329.pdf","host_type":"publisher"},{"url":"https://doi.org/10.2337/db24-0329","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39561322","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11755684","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11755684/","host_type":"repository"},{"url":"https://diabetesjournals.figshare.com/articles/figure/_b_Proteomic_Signature_of_Body_Mass_Index_and_Risk_of_Type_2_Diabetes_b_/27764244/1/files/50530782.pdf","host_type":"Unpaywall"}],"fields_of_study":["Adipokines, Inflammation, and Metabolic Diseases","Advanced Proteomics Techniques and Applications","Nutritional Studies and Diet"],"mesh_terms":[],"keywords":["Body mass index","Type 2 diabetes","Hazard ratio","Medicine","Internal medicine","Obesity","Quartile","Waist","Diabetes mellitus","Framingham Risk Score","Biobank","Bioinformatics","Endocrinology","Biology","Confidence interval","Disease"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:51:29.449573Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}