{"doi":"10.21203/rs.2.21466/v1","title":"Associations of leptin with incident type 2 diabetes and interactions among African Americans: the Jackson Heart Study","abstract":"Abstract Background: Growing evidence suggests that leptin is critical for glycemic control. We assessed the association of leptin and adiponectin with incident type 2 diabetes (T2D), their interactions with sex and obesity status, and mediation by insulin resistance. Methods: Study participants from the Jackson Heart Study, a prospective cohort of adult African Americans in Jackson, Mississippi, included those free of T2D at the baseline Exam 1. Incident T2D was defined as new cases at Exam 2 or Exam 3. We created separate Cox regression models (hazard ratios per log-transformed ng/mL of leptin) with and without insulin resistance, HOMA-IR. Mediation by insulin resistance was analyzed. Several interactions were assessed, including by sex, HbA1c, and obesity. Results: Among 3,363 participants (mean age 53 years, 63% women), 584 developed incident T2D. Leptin was associated with incident T2D when modeled without HOMA-IR (HR=1.32, 95% CI=1.08-1.61). Among men, this positive association between leptin and T2D was significant (HR=1.33, 95% CI=1.05-1.69), but it was nonsignificant among women (HR=1.24, 95% CI=0.94-1.64); statistical interaction with sex was nonsignificant (p=0.65). The associations in all participants and in men were nullified by HOMA-IR (HR=0.99, 95% CI=0.80-1.22; HR=1.00, 95% CI=0.78-1.28, respectively), indicating mediation through insulin resistance (proportion mediated: 1.04), and were not observed in abdominally obese participants. Conclusions: The leptin and incident T2D association mediated by insulin resistance was observed only among abdominally non-obese African Americans in the Jackson Heart Study, suggestive of a ‘leptin resistance’ phenomenon. Differences by sex appeared: men showed a significant association mediated by insulin resistance.","journal":"Research Square","year":2020,"id":134443,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5331,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":361382,"name":"Paul C. Dinh","orcid":"0000-0003-0235-8519","position":1,"is_corresponding":false},{"id":476270,"name":"Shabir Sarwary","orcid":null,"position":2,"is_corresponding":false},{"id":476271,"name":"Emily Forsyth","orcid":null,"position":3,"is_corresponding":false},{"id":433882,"name":"Maya Luetke","orcid":"0000-0001-6793-245X","position":4,"is_corresponding":false},{"id":475413,"name":"David B. King","orcid":"0000-0001-6906-0982","position":5,"is_corresponding":false},{"id":272405,"name":"Jiankang Liu","orcid":"0000-0003-1207-5037","position":6,"is_corresponding":false},{"id":578953,"name":"Sharon K. Davis","orcid":null,"position":7,"is_corresponding":false},{"id":1046,"name":"Adolfo Correa","orcid":"0000-0002-9501-600X","position":8,"is_corresponding":false},{"id":435655,"name":"Aurelian Bidulescu","orcid":"0000-0001-8211-8309","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:16:24.540681Z","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":[]}