{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:00:35Z","timestamp":1775804435580,"version":"3.50.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Elucidating the role of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) in pancreatic \u03b2-cell dysfunction is essential for understanding the pathophysiology of type 2 diabetes mellitus (T2DM) and improving clinical risk assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate associations between protein expression level of HIF-1\u03b1 in peripheral blood and key glycemic parameters\u2014fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin (FINS), and the homeostatic model assessment of insulin resistance (HOMA-IR)\u2014in patients with T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>PubMed, Embase, Cochrane Library, Web of Science (WOS), Wanfang, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) were searched from inception to July 28, 2025, for Chinese and English publications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study selection<\/jats:title>\n                    <jats:p>Observational studies examining the relationship between HIF-1\u03b1 levels and glycemic outcomes in T2DM populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data extraction and synthesis<\/jats:title>\n                    <jats:p>Two reviewers independently extracted data and assessed study quality using AHRQ criteria. Random-effects meta-analysis was used to calculate mean differences (MD) with 95% confidence intervals (CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcomes and measures<\/jats:title>\n                    <jats:p>Differences in FPG, HbA1c, FINS, and HOMA-IR between high and low HIF-1\u03b1 groups with T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-six studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f5,979) were included. Elevated peripheral HIF-1\u03b1 was significantly associated with increased FPG (MD\u202f=\u202f1.13, 95% CI [0.59, 1.67]), HbA1c (MD\u202f=\u202f0.93, 95% CI [0.63, 1.24]), FINS (MD\u202f=\u202f1.13, 95% CI [0.24, 2.02]), and HOMA-IR (MD\u202f=\u202f1.40, 95% CI [0.62, 2.18]). Subgroup analysis indicated that geographic location significantly modified the FPG association (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0105). Sensitivity analyses confirmed the robustness of these findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Elevated peripheral HIF-1\u03b1 levels correlate with impaired \u03b2-cell function and increased insulin resistance. The discordance between elevated systemic levels and known tissue-specific reductions suggests that peripheral HIF-1\u03b1 may reflect a compensatory response to hypoxia rather than a primary driver of T2DM pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251118501<\/jats:ext-link>\n                      , CRD420251118501.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1763090","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:05:03Z","timestamp":1775801103000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of peripheral blood HIF-1\u03b1 in pancreatic \u03b2-cell dysfunction and insulin resistance among patients with type 2 diabetes: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yi","family":"Su","sequence":"first","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Peng","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Luo","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingzhi","family":"Liang","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianglong","family":"Li","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulin","family":"Leng","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"TCM Prevention and Treatment of Metabolic and Chronic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxu","family":"Fu","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"TCM Prevention and Treatment of Metabolic and Chronic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunguang","family":"Xie","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"TCM Prevention and Treatment of Metabolic and Chronic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/s0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the global burden of disease study 2021","volume":"402","year":"2023","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 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