{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T07:57:14Z","timestamp":1785571034249,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sodium\u2013glucose cotransporter 2 inhibitors reduce cardiovascular and renal events beyond glucose lowering, but their hematocrit\u2010raising effects raise concerns about increased blood viscosity and microvascular impairment. We investigated whether dapagliflozin adversely affects microvascular hemorheology in patients with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In this multicenter, open\u2010label, randomized controlled trial, 82 adults with type 2 diabetes received dapagliflozin (5\u2009mg\/day) or conventional therapy for 16\u2009weeks. The primary endpoint was the change in whole blood passage time (WBPT), measured using a microchannel flow analyzer that simulates precapillary arterioles (7\u2009\u00d7\u20097\u2009\u03bcm), with a prespecified noninferiority margin of 6.0\u2009s (15%). Secondary outcomes included apparent microvascular viscosity, adhesive leukocyte count, and oxidative stress markers. Serum erythropoietin (EPO) was evaluated in an ancillary analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WBPT changed minimally in the dapagliflozin group (+1.4\u2009s; 95% CI, 0.0\u20132.9) and slightly decreased in the control group (\u22120.6\u2009s; 95% CI, \u22121.9 to 0.6), yielding a between\u2010group difference of 2.0\u2009s (95% CI, \u22120.2 to 3.9), with the upper bound below the prespecified noninferiority margin. Microvascular viscosity, hematocrit\u2010standardized viscosity, leukocyte adhesion, and oxidative stress markers remained stable in both groups. Dapagliflozin increased hematocrit and EPO, particularly in participants with lower baseline hematocrit, whereas those with hematocrit &gt;45% showed minimal change.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dapagliflozin did not impair microvascular hemorheology despite modest increases in hematocrit and EPO. These findings support the microvascular safety of dapagliflozin and reinforce its role in cardio\u2013renal risk management in type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70344","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:02:18Z","timestamp":1779447738000},"page":"1322-1334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dapagliflozin does not impair microvascular hemorheology in type 2 diabetes mellitus: A\u00a0multicenter randomized controlled trial (D\u2010\n                    <scp>PATH<\/scp>\n                    study)"],"prefix":"10.1111","volume":"17","author":[{"given":"Yuki","family":"Nakatani","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Banba","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoya","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Nephrology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Turumi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Nephrology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Hoshiai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Nephrology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takushi","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Nephrology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Tomoe","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Nephrology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Tamiya","sequence":"additional","affiliation":[{"name":"Institute for Human Movement and Medical Sciences Niigata University of Health and Welfare  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Otani","sequence":"additional","affiliation":[{"name":"Department of Cardiology Dokkyo Medical University Nikko Medical Center  Nikko Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sugimura","sequence":"additional","affiliation":[{"name":"Department of Cardiology Dokkyo Medical University Nikko Medical Center  Nikko Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Ikemiyagi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nephrology and Neurology University of the Ryukyus  Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ohya","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nephrology and Neurology University of the Ryukyus  Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Yokokawa Clinic  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics University of the Ryukyus Graduate School of Medicine  Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-1999","authenticated-orcid":false,"given":"Yoshimasa","family":"Aso","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Dokkyo Medical University  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Maejima","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Nephrology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Yasu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Nephrology Dokkyo Medical University Nikko Medical Center  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01301-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000083252"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1988.tb01003.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052187"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30327-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206286"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107038"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1515920"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038881"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044235"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad235"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.07.014"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(94)90679-3"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.8532481.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwn243"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-8-48"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0695-y"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-207610"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4670-7"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-020-00545-z"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1931.96.3.562"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(80)90050-3"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.43.5.738"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-17-0809"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-10-0440"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000133677.77465.38"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-09-0758"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-019-01486-y"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120311"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-08-0917"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.153056"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2001.118467"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19586"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-05876-w"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.02.004"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02481-y"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13126"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30162-5"}],"container-title":["Journal of Diabetes Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.70344","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jdi.70344","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.70344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T06:58:17Z","timestamp":1785567497000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdi.70344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/jdi.70344"],"URL":"https:\/\/doi.org\/10.1111\/jdi.70344","archive":["Portico"],"relation":{},"ISSN":["2040-1116","2040-1124"],"issn-type":[{"value":"2040-1116","type":"print"},{"value":"2040-1124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"assertion":[{"value":"2026-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}