{"doi":"10.1210/clinem/dgab760","title":"Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy","abstract":"CONTEXT: Leptin replacement with metreleptin improves glycemia and hypertriglyceridemia in severely hypoleptinemic patients with generalized lipodystrophy (GLD), but its effects are variable in partially leptin-deficient patients with partial lipodystrophy (PLD). OBJECTIVE: Compare 3 leptin assays (Study I); identify diagnostic performance of leptin assays to detect responders to metreleptin for each assay (Study II). DESIGN: Study I: cross-sectional analysis of average bias between leptin assays. Study II: retrospective analysis of diagnostic accuracy of potential leptin cut points to detect clinical responders to metreleptin. SETTING: National Institutes of Health; University of Michigan. PARTICIPANTS AND INTERVENTIONS: Study I: Metreleptin-naïve patients with lipodystrophy (GLD, n = 33, PLD, n = 67) and healthy volunteers (n = 239). Study II: GLD (n = 66) and PLD (n = 84) patients treated with metreleptin for 12 months. OUTCOME MEASURES: Leptin concentrations by Millipore radioimmunoassay (RIA), Millipore enzyme-linked immunosorbent assay (MELISA), and R&D Systems enzyme-linked immunosorbent assay (RDELISA). Response to metreleptin therapy was defined as either reduction ≥1.0% in A1c or ≥30% in serum triglycerides. RESULTS: RDELISA measured 3.0 ± 9.5 ng/mL higher than RIA; MELISA measured 11.0 ± 17.8 and 14.0 ±19.2 less than RIA and RDELISA, respectively. Leptin by RIA, MELISA, and RDELISA modestly predicted metreleptin response in GLD + PLD [receiver operating characteristic (ROC) area under the curve (AUC) 0.74, 0.69, and 0.71, respectively; P < 0.01 for all] with lower predictive power in PLD (ROC AUC 0.63, 0.61 and 0.65, respectively; P > 0.05 for all). The only reproducible cut point identified on sensitivity analyses was RIA leptin 7.2 ng/mL (sensitivity 56%; specificity 78%). CONCLUSIONS: Three common leptin assays are not interchangeable, and a reliable cut point to select responders to metreleptin was not identified.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":180691,"datarank":0.79604981470327,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.3624940510188453,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.3624940510188453,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":13,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00001987","NCT00025883","NCT01778556","NCT00428987","NCT00677313","NCT01679197"]},"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":730128,"name":"Noemi Malandrino","orcid":"0000-0001-5587-1127","position":1,"is_corresponding":false},{"id":234133,"name":"Mary Walter","orcid":null,"position":2,"is_corresponding":false},{"id":699268,"name":"Adam Neidert","orcid":"0009-0000-6444-0417","position":3,"is_corresponding":false},{"id":446037,"name":"Ranganath Muniyappa","orcid":"0000-0003-4198-1055","position":4,"is_corresponding":false},{"id":699270,"name":"Elif A Oral","orcid":"0000-0002-9171-1144","position":5,"is_corresponding":false},{"id":446038,"name":"Rebecca J. Brown","orcid":"0000-0002-2589-7382","position":6,"is_corresponding":false},{"id":699260,"name":"Rasimcan Meral","orcid":"0000-0003-4026-5049","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:47:57.268805Z","pmid":"34677608","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":[]}