{"doi":"10.3389/fmed.2026.1768610","title":"Clinical effects of Yiqi-Yangyin-Huoxue granules in the management of type 2 diabetes mellitus and early vascular aging: a randomized, double-blind, placebo-controlled trial protocol","abstract":"<jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>Type 2 diabetes mellitus (T2DM) has become a major global public health challenge, affecting more than 500 million adults worldwide. Early vascular aging (EVA) is one of the key pathological changes for diabetic vascular complications. However, targeted and effective therapeutic strategies remain limited. Based on our previous research and clinical experience, we developed a granulated natural herbal formulation, Yiqi-Yangyin-Huoxue (YQYYHX). This trial aims to evaluate the clinical efficacy and safety of YQYYHX in patients with T2DM and EVA, and to preliminarily explore its potential mechanisms.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>This is a single-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. It will enroll 120 participants with T2DM and EVA, who will be randomized in a 1:1 allocation ratio to two groups. In addition to standard therapy, the treatment group will receive the YQYYHX granules, while the control group will receive a matched placebo. Based on mass spectrometry analysis, daidzin, salvianolic acid L, and oleamide were identified as the compounds with the largest peak area in YQYYHX. After a 12-week intervention, brachial-ankle pulse wave velocity (baPWV) is planned to be assessed as the primary outcome. Secondary outcomes are expected to include the ankle-brachial index, blood glucose levels, lipid profiles, inflammatory cytokines, 6-min walk test and questionnaires. Safety will be evaluated using liver transaminases, serum creatinine, and related indicators. Serum and fecal samples will be collected before and after treatment. The serum will be used for metabolomic and proteomic sequencing analysis, and feces will be used for metagenomic sequencing. Electronic case report forms are generated within the clinical record system, ensuring that all follow-up information is traceable. Subsequently, the data will be entered into a specific electronic data capture, and the data administrator will verify it.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>The recruitment began on March 27, 2025 and is expected to end on December 31, 2026. As of March 10, 2026, 72 participants have been enrolled.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>This rigorously designed trial is expected to generate reliable evidence. As a complementary and alternative therapeutic option, YQYYHX has the potential to benefit patients with T2DM and EVA.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration</jats:title>\n                    <jats:p>\n                      This trial has been registered with the International Traditional Medicine Clinical Trial Registry Platform (\n                      <jats:ext-link>http://itmctr.ccebtcm.org.cn/</jats:ext-link>\n                      , ITMCTR2024000388).\n                    </jats:p>\n                  </jats:sec>","journal":"Frontiers in Medicine","year":2026,"id":604727,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":115277,"name":"Yifei Qi","orcid":"0000-0003-2853-7910","position":1,"is_corresponding":false},{"id":1551664,"name":"Jingyi Zhan","orcid":null,"position":2,"is_corresponding":false},{"id":1551665,"name":"Linjing Su","orcid":null,"position":3,"is_corresponding":false},{"id":1551666,"name":"Yucong Gao","orcid":null,"position":4,"is_corresponding":false},{"id":1551667,"name":"Qingbing Zhou","orcid":null,"position":5,"is_corresponding":false},{"id":832049,"name":"Ying Zhang","orcid":"0000-0003-2194-7116","position":6,"is_corresponding":false},{"id":1551663,"name":"Jinyi Fu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Clinical effects of Yiqi-Yangyin-Huoxue granules in the management of type 2 diabetes mellitus and early vascular aging: a randomized, double-blind, placebo-controlled trial protocol","abstract":"<jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>Type 2 diabetes mellitus (T2DM) has become a major global public health challenge, affecting more than 500 million adults worldwide. Early vascular aging (EVA) is one of the key pathological changes for diabetic vascular complications. However, targeted and effective therapeutic strategies remain limited. Based on our previous research and clinical experience, we developed a granulated natural herbal formulation, Yiqi-Yangyin-Huoxue (YQYYHX). This trial aims to evaluate the clinical efficacy and safety of YQYYHX in patients with T2DM and EVA, and to preliminarily explore its potential mechanisms.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>This is a single-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. It will enroll 120 participants with T2DM and EVA, who will be randomized in a 1:1 allocation ratio to two groups. In addition to standard therapy, the treatment group will receive the YQYYHX granules, while the control group will receive a matched placebo. Based on mass spectrometry analysis, daidzin, salvianolic acid L, and oleamide were identified as the compounds with the largest peak area in YQYYHX. After a 12-week intervention, brachial-ankle pulse wave velocity (baPWV) is planned to be assessed as the primary outcome. Secondary outcomes are expected to include the ankle-brachial index, blood glucose levels, lipid profiles, inflammatory cytokines, 6-min walk test and questionnaires. Safety will be evaluated using liver transaminases, serum creatinine, and related indicators. Serum and fecal samples will be collected before and after treatment. The serum will be used for metabolomic and proteomic sequencing analysis, and feces will be used for metagenomic sequencing. Electronic case report forms are generated within the clinical record system, ensuring that all follow-up information is traceable. Subsequently, the data will be entered into a specific electronic data capture, and the data administrator will verify it.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>The recruitment began on March 27, 2025 and is expected to end on December 31, 2026. As of March 10, 2026, 72 participants have been enrolled.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>This rigorously designed trial is expected to generate reliable evidence. As a complementary and alternative therapeutic option, YQYYHX has the potential to benefit patients with T2DM and EVA.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration</jats:title>\n                    <jats:p>\n                      This trial has been registered with the International Traditional Medicine Clinical Trial Registry Platform (\n                      <jats:ext-link>http://itmctr.ccebtcm.org.cn/</jats:ext-link>\n                      , ITMCTR2024000388).\n                    </jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42318385","pmcid":"PMC13273645","openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1768610/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fmed.2026.1768610/full","host_type":"publisher"},{"url":"https://doaj.org/article/c8a04ac39a024e098b4a9dc97e6d7baa","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13273645/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC13273645","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC13273645?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":[],"keywords":["Type 2 diabetes","Traditional medicine","Clinical Protocol","Bapwv","Early Vascular Aging","Yiqi-yangyin-huoxue Granule"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T00:48:18.461214Z","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":[]}