{"doi":"10.2337/dc21-0737","title":"Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes","abstract":"<jats:sec><jats:title>OBJECTIVES</jats:title><jats:p>Patients with type 1 diabetes (T1D) exhibit modest lipid abnormalities as measured by traditional metrics. This study aimed to identify lipidomic predictors of rapid decline of kidney function in T1D.</jats:p></jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS</jats:title><jats:p>In a case-control study, 817 patients with T1D from three large cohorts were randomly split into training and validation subsets. Case was defined as &amp;gt;3 mL/min/1.73 m2 per year decline in estimated glomerular filtration rate (eGFR), while control was defined as &amp;lt;1 mL/min/1.73 m2 per year decline over a minimum 4-year follow-up. Lipids were quantified in baseline serum samples using a targeted mass spectrometry lipidomic platform.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>At individual lipids, free fatty acid (FFA)20:2 was directly and phosphatidylcholine (PC)16:0/22:6 was inversely and independently associated with rapid eGFR decline. When examined by lipid class, rapid eGFR decline was characterized by higher abundance of unsaturated FFAs, phosphatidylethanolamine (PE)-Ps, and PCs with an unsaturated acyl chain at the sn1 carbon, and by lower abundance of saturated FFAs, longer triacylglycerols, and PCs, PEs, PE-Ps, and PE-Os with an unsaturated acyl chain at the sn1 carbon at eGFR ≥90 mL/min/1.73 m2. A multilipid panel consisting of unsaturated FFAs and saturated PE-Ps predicted rapid eGFR decline better than individual lipids (C-statistic, 0.71) and improved the C-statistic of the clinical model from 0.816 to 0.841 (P = 0.039). Observations were confirmed in the validation subset.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>Distinct from previously reported predictors of GFR decline in type 2 diabetes, these findings suggest differential incorporation of FFAs at the sn1 carbon of the phospholipids’ glycerol backbone as an independent predictor of rapid GFR decline in T1D.</jats:p></jats:sec>","journal":"Diabetes Care","year":2021,"id":649693,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"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":327427,"name":"Thekkelnaycke M. Rajendiran","orcid":null,"position":1,"is_corresponding":false},{"id":780523,"name":"Chenchen He","orcid":"0000-0002-0500-1526","position":2,"is_corresponding":false},{"id":433357,"name":"Jaeman Byun","orcid":null,"position":3,"is_corresponding":false},{"id":292965,"name":"Daniel Montemayor","orcid":"0000-0001-8702-5646","position":4,"is_corresponding":false},{"id":292963,"name":"Manjula Darshi","orcid":"0000-0002-1373-7488","position":5,"is_corresponding":false},{"id":1693759,"name":"Jana Tumova","orcid":null,"position":6,"is_corresponding":false},{"id":1062825,"name":"Jiwan Kim","orcid":"0009-0006-2086-1387","position":7,"is_corresponding":false},{"id":481576,"name":"Christine P. Limonte","orcid":"0000-0002-9162-7428","position":8,"is_corresponding":false},{"id":382894,"name":"Rachel G. Miller","orcid":"0000-0003-1845-8477","position":9,"is_corresponding":false},{"id":439760,"name":"Tina Costacou","orcid":"0000-0001-9303-3810","position":10,"is_corresponding":false},{"id":309261,"name":"Trevor J. Orchard","orcid":"0000-0001-9552-3215","position":11,"is_corresponding":false},{"id":116243,"name":"Tarunveer S. Ahluwalia","orcid":"0000-0002-7464-3354","position":12,"is_corresponding":false},{"id":42050,"name":"Peter Rossing","orcid":"0000-0002-1531-4294","position":13,"is_corresponding":false},{"id":1380279,"name":"Janet K. Snell-Bergeon","orcid":null,"position":14,"is_corresponding":false},{"id":231201,"name":"Ian H. de Boer","orcid":"0000-0003-1571-7592","position":15,"is_corresponding":false},{"id":225266,"name":"Loki Natarajan","orcid":"0000-0001-5719-828X","position":16,"is_corresponding":false},{"id":514917,"name":"George Michailidis","orcid":"0000-0002-3676-1739","position":17,"is_corresponding":false},{"id":292969,"name":"Kumar Sharma","orcid":"0000-0002-7550-8525","position":18,"is_corresponding":false},{"id":263300,"name":"Subramaniam Pennathur","orcid":"0000-0003-3628-6883","position":19,"is_corresponding":false},{"id":480602,"name":"Farsad Afshinnia","orcid":"0000-0003-3051-3141","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes","abstract":"<jats:sec><jats:title>OBJECTIVES</jats:title><jats:p>Patients with type 1 diabetes (T1D) exhibit modest lipid abnormalities as measured by traditional metrics. This study aimed to identify lipidomic predictors of rapid decline of kidney function in T1D.</jats:p></jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS</jats:title><jats:p>In a case-control study, 817 patients with T1D from three large cohorts were randomly split into training and validation subsets. Case was defined as &amp;gt;3 mL/min/1.73 m2 per year decline in estimated glomerular filtration rate (eGFR), while control was defined as &amp;lt;1 mL/min/1.73 m2 per year decline over a minimum 4-year follow-up. Lipids were quantified in baseline serum samples using a targeted mass spectrometry lipidomic platform.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>At individual lipids, free fatty acid (FFA)20:2 was directly and phosphatidylcholine (PC)16:0/22:6 was inversely and independently associated with rapid eGFR decline. When examined by lipid class, rapid eGFR decline was characterized by higher abundance of unsaturated FFAs, phosphatidylethanolamine (PE)-Ps, and PCs with an unsaturated acyl chain at the sn1 carbon, and by lower abundance of saturated FFAs, longer triacylglycerols, and PCs, PEs, PE-Ps, and PE-Os with an unsaturated acyl chain at the sn1 carbon at eGFR ≥90 mL/min/1.73 m2. A multilipid panel consisting of unsaturated FFAs and saturated PE-Ps predicted rapid eGFR decline better than individual lipids (C-statistic, 0.71) and improved the C-statistic of the clinical model from 0.816 to 0.841 (P = 0.039). Observations were confirmed in the validation subset.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>Distinct from previously reported predictors of GFR decline in type 2 diabetes, these findings suggest differential incorporation of FFAs at the sn1 carbon of the phospholipids’ glycerol backbone as an independent predictor of rapid GFR decline in T1D.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34244329","pmcid":"PMC8740931","openalex_id":"https://openalex.org/W3181710594","authors":[],"funders":[{"funder_name":"Steno Diabetes Center Copenhagen (SDCC)","grant_id":"SDCC 3.A Complications","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK036836","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK020572","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK034818","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL113029","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF18OC0052457","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK017047","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK081943","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"K08 DK106523","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK089503","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R03 DK121941","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK110541","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK116731","title":null}],"total_grants":13,"fwci":4.8533,"citation_percentile":0.9621021,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":13},{"year":2023,"count":10},{"year":2024,"count":8},{"year":2025,"count":3},{"year":2026,"count":4}],"oa_status":"bronze","license":"https://www.diabetesjournals.org/content/license","oa_locations":[{"url":"https://diabetesjournals.org/care/article-pdf/44/9/2098/633273/dc210737.pdf","host_type":"journal"},{"url":"https://diabetesjournals.org/care/article-pdf/44/9/2098/633273/dc210737.pdf","host_type":"publisher"},{"url":"https://doi.org/10.2337/dc21-0737","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34244329","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8740931","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/7dd46711-f81f-4042-a7f8-ae598e15f26c","host_type":"repository"}],"fields_of_study":["Liver Disease Diagnosis and Treatment","Chronic Kidney Disease and Diabetes","Diabetes Management and Research","Case-Control Studies","Diabetes Mellitus, Type 1","Diabetes Mellitus, Type 2","Disease Progression","Fatty Acids, Nonesterified","Glomerular Filtration Rate","Humans","Kidney","Phospholipids","Renal Insufficiency, Chronic","Risk Factors"],"mesh_terms":["Diabetes Mellitus, Type 1","Diabetes Mellitus, Type 2","Fatty Acids, Nonesterified","Glomerular Filtration Rate","Humans","Kidney","Phospholipids","Risk Factors","Case-Control Studies","Disease Progression","Renal Insufficiency, Chronic"],"keywords":["Medicine","Phospholipid","Diabetes mellitus","Renal function","Internal medicine","Type 2 diabetes","Fatty acid","Endocrinology","Biochemistry","Biology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T04:10:09.677191Z","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":[]}