{"doi":"10.1111/dom.70037","title":"Acidosis is associated with lower insulin sensitivity and incident type 2 diabetes in indigenous Americans: A prospective cohort study","abstract":"AIM: Whether markers of acid accumulation [decreased plasma bicarbonate, increased anion gap (AG) and corrected anion gap (CAG)] are associated with insulin sensitivity and alter diabetes risk is unclear. We aimed to examine the association of these markers with the gold-standard measure of insulin sensitivity and incident type 2 diabetes. MATERIALS AND METHODS: Healthy adults without diabetes enrolled in a longitudinal study had baseline measures of acidosis (bicarbonate, AG, CAG), insulin sensitivity by hyperinsulinaemic-euglycaemic clamp, and body composition. In cross-sectional analysis (n = 296, 188 male), the relationship between acid markers and insulin sensitivity (M-low) was evaluated. Progression to type 2 diabetes was evaluated by Cox regression models (per 1-SD change) in those with appropriate follow-up visits (n = 233). RESULTS: Increased AG and CAG were associated with lower M-low, adjusting for age, sex, body fat (%) and estimated glomerular filtration rate (AG: partial r = -0.22, CAG: partial r = -0.24, both p < 0.0001) but not with bicarbonate. During a median follow-up time of 8.0 years, 50 participants developed type 2 diabetes. CAG was associated with increased risk of type 2 diabetes (HR: 1.32, 95% CI 1.01-1.74, p = 0.044) in a model adjusted for age, sex, body fat (%) and baseline plasma glucose, but not after further adjusting for M-low (p = 0.17). Bicarbonate and AG were not associated with risk of diabetes. CONCLUSION: Acidosis was associated with lower insulin sensitivity and increased risk of type 2 diabetes that was attenuated by measures of lower insulin sensitivity. Acidosis as reflected by CAG may be a target for intervention.","journal":"Diabetes Obesity and Metabolism","year":2025,"id":553884,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8111,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":928809,"name":"Tomás Cabeza de Baca","orcid":"0000-0003-3322-2163","position":1,"is_corresponding":false},{"id":445466,"name":"Emma J. Stinson","orcid":"0000-0003-4875-7048","position":2,"is_corresponding":false},{"id":445467,"name":"Marci E. Gluck","orcid":"0000-0002-6284-9953","position":3,"is_corresponding":false},{"id":260537,"name":"Paolo Piaggi","orcid":"0000-0003-2774-9161","position":4,"is_corresponding":false},{"id":260540,"name":"Jonathan Krakoff","orcid":"0000-0001-6074-5600","position":5,"is_corresponding":false},{"id":366152,"name":"Douglas C. Chang","orcid":"0000-0003-4591-9056","position":6,"is_corresponding":false},{"id":1152841,"name":"Andrés M. Treviño‐Alvarez","orcid":"0000-0001-9405-3338","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"40826913","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":[]}