{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:29:09Z","timestamp":1780547349090,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK069015\u201036"],"award-info":[{"award-number":["DK069015\u201036"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK069028"],"award-info":[{"award-number":["DK069028"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>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\u2010standard measure of insulin sensitivity and incident type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Healthy adults without diabetes enrolled in a longitudinal study had baseline measures of acidosis (bicarbonate, AG, CAG), insulin sensitivity by hyperinsulinaemic\u2010euglycaemic clamp, and body composition. In cross\u2010sectional analysis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009296, 188 male), the relationship between acid markers and insulin sensitivity (M\u2010low) was evaluated. Progression to type 2 diabetes was evaluated by Cox regression models (per 1\u2010SD change) in those with appropriate follow\u2010up visits (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009233).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increased AG and CAG were associated with lower M\u2010low, adjusting for age, sex, body fat (%) and estimated glomerular filtration rate (AG: partial\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.22, CAG: partial\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.24, both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) but not with bicarbonate. During a median follow\u2010up time of 8.0\u2009years, 50 participants developed type 2 diabetes. CAG was associated with increased risk of type 2 diabetes (HR: 1.32, 95% CI 1.01\u20131.74,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.044) in a model adjusted for age, sex, body fat (%) and baseline plasma glucose, but not after further adjusting for M\u2010low (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.17). Bicarbonate and AG were not associated with risk of diabetes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70037","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T05:54:54Z","timestamp":1755582894000},"page":"6440-6448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Acidosis is associated with lower insulin sensitivity and incident type 2 diabetes in indigenous Americans: A prospective cohort study"],"prefix":"10.1111","volume":"27","author":[{"given":"Andr\u00e9s M.","family":"Trevi\u00f1o\u2010Alvarez","sequence":"first","affiliation":[{"name":"Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Phoenix Arizona USA"},{"name":"Department of Neurology Universidad Autonoma de Nuevo Leon  Monterrey M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3322-2163","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Cabeza de Baca","sequence":"additional","affiliation":[{"name":"Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J.","family":"Stinson","sequence":"additional","affiliation":[{"name":"Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marci E.","family":"Gluck","sequence":"additional","affiliation":[{"name":"Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-9161","authenticated-orcid":false,"given":"Paolo","family":"Piaggi","sequence":"additional","affiliation":[{"name":"Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Phoenix Arizona USA"},{"name":"Department of Information Engineering University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Krakoff","sequence":"additional","affiliation":[{"name":"Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases National 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