{"doi":"10.1002/acn3.51367","title":"Plasma lipid metabolites associate with diabetic polyneuropathy in a cohort with type 2 diabetes","abstract":"OBJECTIVE: The global rise in type 2 diabetes is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy is the most frequent type 2 diabetes complication and is associated with poor outcomes. The metabolic syndrome has emerged as a major risk factor for diabetic polyneuropathy; however, the metabolites associated with the metabolic syndrome that correlate with diabetic polyneuropathy are unknown. METHODS: We conducted a global metabolomics analysis on plasma samples from a subcohort of participants from the Danish arm of Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION-Denmark) with and without diabetic polyneuropathy versus lean control participants. RESULTS: Compared to lean controls, type 2 diabetes participants had significantly higher HbA1c (p = 0.0028), BMI (p = 0.0004), and waist circumference (p = 0.0001), but lower total cholesterol (p = 0.0001). Out of 991 total metabolites, we identified 15 plasma metabolites that differed in type 2 diabetes participants by diabetic polyneuropathy status, including metabolites belonging to energy, lipid, and xenobiotic pathways, among others. Additionally, these metabolites correlated with alterations in plasma lipid metabolites in type 2 diabetes participants based on neuropathy status. Further evaluating all plasma lipid metabolites identified a shift in abundance, chain length, and saturation of free fatty acids in type 2 diabetes participants. Importantly, the presence of diabetic polyneuropathy impacted the abundance of plasma complex lipids, including acylcarnitines and sphingolipids. INTERPRETATION: Our explorative study suggests that diabetic polyneuropathy in type 2 diabetes is associated with novel alterations in plasma metabolites related to lipid metabolism.","journal":"Annals of Clinical and Translational Neurology","year":2021,"id":155075,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282916,"name":"Kai Guo","orcid":"0000-0002-4651-781X","position":1,"is_corresponding":false},{"id":588154,"name":"Fadhl Alakwaa","orcid":"0000-0001-5349-7960","position":2,"is_corresponding":false},{"id":621027,"name":"Signe T. Andersen","orcid":"0000-0001-5183-3502","position":3,"is_corresponding":false},{"id":277439,"name":"Evan L. Reynolds","orcid":"0000-0002-0138-8436","position":4,"is_corresponding":false},{"id":11248,"name":"Marit E. Jørgensen","orcid":"0000-0001-8356-5565","position":5,"is_corresponding":false},{"id":656791,"name":"Daniel R. Witte","orcid":"0000-0002-0769-2922","position":6,"is_corresponding":false},{"id":621029,"name":"Hatice Tankişi","orcid":"0000-0001-8495-9769","position":7,"is_corresponding":false},{"id":621038,"name":"Morten Charles","orcid":"0000-0003-0327-9564","position":8,"is_corresponding":false},{"id":263298,"name":"Masha G. Savelieff","orcid":"0000-0001-5575-2494","position":9,"is_corresponding":false},{"id":255267,"name":"Brian C. Callaghan","orcid":"0000-0002-8885-6748","position":10,"is_corresponding":false},{"id":621024,"name":"Troels S. Jensen","orcid":"0000-0002-3487-6380","position":11,"is_corresponding":false},{"id":255269,"name":"Eva L. Feldman","orcid":"0000-0002-9162-2694","position":12,"is_corresponding":false},{"id":304441,"name":"Amy E. Rumora","orcid":"0000-0002-0788-3251","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:43:59.154159Z","pmid":"33955722","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":[]}