{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:30:23Z","timestamp":1791822623360,"version":"4.3.4"},"reference-count":137,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T00:00:00Z","timestamp":1470182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diabetes patients have more than double the risk of ischemic stroke compared with non\u2010diabetic individuals, and its neuroimaging characteristics have important clinical implications. To understand the pathophysiology of ischemic stroke in diabetes, it is important to focus not only on the stroke subtype, but also on the size and location of the occlusive vessels. Specifically, ischemic stroke in diabetes patients might be attributed to both large and small vessels, and intracranial internal carotid artery disease and small infarcts of the posterior circulation often occur. An additional feature is that asymptomatic lacunar infarctions are often seen in the basal ganglia and brain stem on brain magnetic resonance imaging. In particular, cerebral small vessel disease (SVD), including lacunar infarctions, white matter lesions and cerebral microbleeds, has been shown to be associated not only with stroke incidence, but also with the development and progression of dementia and diabetic microangiopathy. However, the pathogenesis of cerebral SVD is not fully understood. In addition, data on the association between neuroimaging findings of the cerebral SVD and diabetes are limited. Recently, the clinical importance of the link between cerebral SVD and retinal microvascular abnormalities has been a topic of considerable interest. Several clinical studies have shown that retinal microvascular abnormalities are closely related to cerebral SVD, suggesting that retinal microvascular abnormalities might be pathophysiologically linked to ischemic cerebral SVD. We review the literature relating to the pathophysiology and neuroimaging of cerebrovascular disease in diabetes, and discuss the problems based on the concept of cerebral large and small vessel disease.<\/jats:p>","DOI":"10.1111\/jdi.12545","type":"journal-article","created":{"date-parts":[[2016,5,30]],"date-time":"2016-05-30T09:56:43Z","timestamp":1464602203000},"page":"134-148","source":"Crossref","is-referenced-by-count":92,"title":["Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities"],"prefix":"10.1111","volume":"8","author":[{"given":"Toshitaka","family":"Umemura","sequence":"first","affiliation":[{"name":"Department of Neurology Chubu Rosai Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrine Internal Medicine Chubu Rosai Hospital Nagoya Japan"},{"name":"Department of Preventive Medical Center Chubu Rosai Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigishi","family":"Hotta","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrine Internal Medicine Chubu Rosai Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1979.03290450033020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1987.03390070069025"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410220307"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.490"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60484-9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70340-0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-197304000-00001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8227(94)90250-X"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/hs1101.098520"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70104-6"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2010.08.042"},{"key":"e_1_2_10_13_1","first-page":"89","article-title":"New concepts and insights on pathogenesis and treatment of diabetic complications: polyol pathway and its inhibition","volume":"60","author":"Hotta N","year":"1997","journal-title":"Nagoya J Med Sci"},{"key":"e_1_2_10_14_1","first-page":"123A","article-title":"Aldose reductase inhibitor can improve diabetic retinopathy in experimental and clinical studies","volume":"37","author":"Hotta N","year":"1988","journal-title":"Diabetes"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1455"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq127"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.24.1.35"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000123252.55688.05"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.641381"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.22.2.155"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000069936"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.6.1153"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051007"},{"key":"e_1_2_10_24_1","first-page":"867","volume-title":"Joslin's Diabetes Mellitus","author":"Feener EP","year":"2005"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.11.012"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.08.006"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12250"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945008783431781"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.42.11.1594"},{"key":"e_1_2_10_30_1","first-page":"541","article-title":"An aldose reductase inhibitor, TAT, reduces ADP\u2010induced platelet hyperaggregation in streptozotocin\u2010induced diabetic rats with neuropathy","volume":"126","author":"Hara T","year":"1995","journal-title":"J Lab Clin Med"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1111"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051310"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051646"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24819"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2006.01946.x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600452"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.158295"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22349"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00137.2010"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.226902"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59291"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0032"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc05-2370"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040-1124.2010.00037.x"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2012.03684.x"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000063318.66140.A3"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.6.809"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.27.1.37"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901073400103"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000226399.13528.0a"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.106.480830"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0327"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.03.018"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.003508"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.584672"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.496513"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.15.8.774"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(98)00106-5"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.005018"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2011.05.017"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(98)00103-X"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.9.1246"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.02.006"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.003164"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000148477.65273.0C"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.583534"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.001467"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002491"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.011889"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70170-9"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.005919"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.10.1932"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1161\/hs0102.101629"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.498535"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-1637"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.04.06.db05-1323"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1159\/000098054"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0688-y"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720208784310213"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1923"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f25f06"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0555"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0143"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000058480.77236.B3"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.172072"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.1.70"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000319691.50117.54"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0493"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0348"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.506337"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.559567"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.04.008"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0250"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2005.10.007"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2010.217380"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2008.07.006"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000307750.41970.d9"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70013-4"},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(05)70284-2"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1235-0"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0922"},{"key":"e_1_2_10_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.03.038"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2935"},{"key":"e_1_2_10_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2011.07.002"},{"key":"e_1_2_10_105_1","first-page":"491","article-title":"Factors associated with brain atrophy estimated with automatic voxel\u2010based morphometry of structural magnetic resonance images in elderly diabetic patients: impact of albuminuria on hippocampal atrophy","volume":"6","author":"Kawamura T","year":"2015","journal-title":"J Diabetes Metab"},{"key":"e_1_2_10_106_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f4d7f8"},{"key":"e_1_2_10_107_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1163"},{"key":"e_1_2_10_108_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000269"},{"key":"e_1_2_10_109_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040-1124.2012.00234.x"},{"key":"e_1_2_10_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2011.06.014"},{"key":"e_1_2_10_111_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.594267"},{"key":"e_1_2_10_112_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0969"},{"key":"e_1_2_10_113_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000257815.20548.df"},{"key":"e_1_2_10_114_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318248e50f"},{"key":"e_1_2_10_115_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.08.022"},{"key":"e_1_2_10_116_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443497"},{"key":"e_1_2_10_117_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.496091"},{"key":"e_1_2_10_118_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a60a71"},{"key":"e_1_2_10_119_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.580837"},{"key":"e_1_2_10_120_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182020349"},{"key":"e_1_2_10_121_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21549"},{"key":"e_1_2_10_122_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.153460"},{"key":"e_1_2_10_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70131-0"},{"key":"e_1_2_10_124_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2141"},{"key":"e_1_2_10_125_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12234"},{"key":"e_1_2_10_126_1","first-page":"169","volume-title":"Diabetic Retinopathy","author":"Bek T","year":"2000"},{"key":"e_1_2_10_127_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1967.00980030135005"},{"key":"e_1_2_10_128_1","first-page":"303","article-title":"The nature of conjunctival microaneurysms: clinical and electron microscopic","volume":"17","author":"Chazan BL","year":"1968","journal-title":"Diabetes"},{"key":"e_1_2_10_129_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6612330"},{"key":"e_1_2_10_130_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.33.1.97"},{"key":"e_1_2_10_131_1","first-page":"2285","article-title":"Diabetic\u2010like retinopathy in rats prevented with an aldose reductase inhibitor","volume":"30","author":"Robison WG","year":"1989","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_10_132_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(89)90057-2"},{"key":"e_1_2_10_133_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1995.tb01972.x"},{"key":"e_1_2_10_134_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.2000.0882"},{"key":"e_1_2_10_135_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.33.6.562"},{"key":"e_1_2_10_136_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.29.6.450"},{"key":"e_1_2_10_137_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00270423"},{"key":"e_1_2_10_138_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000077408.15865.06"}],"container-title":["Journal of Diabetes Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjdi.12545","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjdi.12545","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.12545","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T09:50:18Z","timestamp":1695462618000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdi.12545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,3]]},"references-count":137,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1111\/jdi.12545"],"URL":"https:\/\/doi.org\/10.1111\/jdi.12545","archive":["Portico"],"relation":{},"ISSN":["2040-1116","2040-1124"],"issn-type":[{"value":"2040-1116","type":"print"},{"value":"2040-1124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,3]]}}}