{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:36:12Z","timestamp":1773794172446,"version":"3.50.1"},"reference-count":83,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81560147"],"award-info":[{"award-number":["81560147"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    It remains unclear whether cholesterol\u2010lowering therapy can reduce the incidence of microvascular complications in patients with diabetes. We aim to explore the potential causal relationship between three common types of cholesterol\u2010lowering drugs and diabetic microvascular complications through drug\u2010target Mendelian randomization (MR) study, laying the groundwork for the development of new medications.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    In this study, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR (3\u2010hydroxy\u20103\u2010methylglutaryl\u2010CoA reductase) inhibitors, PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibitors, and NPC1L1 (Niemann\u2013Pick C1\u2010Like 1) inhibitors from published genome\u2010wide association study statistics. Subsequently, drug\u2010target MR analyses were performed to investigate the effects of these inhibitors on low\u2010density lipoprotein cholesterol (LDL\u2010C) level\u2013mediated microvascular complications in diabetes mellitus. Coronary atherosclerosis as a positive control. Primary outcomes included diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy from the FinnGen Consortium.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The MR analysis revealed significant associations between HMGCR inhibition and increased risks of diabetic nephropathy (OR\u2009[95\n                    <jats:italic>%<\/jats:italic>\n                    confidence\u2009interval\u2009(CI)] = 1.88 [1.50, 2.36],\n                    <jats:italic>p<\/jats:italic>\n                    = 5.55 \u00d7 10\n                    <jats:sup>\u20138<\/jats:sup>\n                    ), retinopathy (OR\u2009[95\n                    <jats:italic>%<\/jats:italic>\n                    CI] = 1.86 [1.54, 2.24],\n                    <jats:italic>p<\/jats:italic>\n                    = 6.28 \u00d7 10\n                    <jats:sup>\u201311<\/jats:sup>\n                    ), and neuropathy (OR\u2009[95\n                    <jats:italic>%<\/jats:italic>\n                    CI] = 2.63 [1.84, 3.75],\n                    <jats:italic>p<\/jats:italic>\n                    = 1.14 \u00d7 10\n                    <jats:sup>\u20137<\/jats:sup>\n                    ) using the inverse variance weighted method. PCSK9 inhibitors have been associated with an increased risk of diabetic nephropathy (OR\u2009[95\n                    <jats:italic>%<\/jats:italic>\n                    CI] = 1.30 [1.07, 1.58],\n                    <jats:italic>p<\/jats:italic>\n                    = 0.009) and diabetic neuropathy (OR\u2009[95\n                    <jats:italic>%<\/jats:italic>\n                    CI] = 1.40 [1.15, 1.72],\n                    <jats:italic>p<\/jats:italic>\n                    = 0.001); NPC1L1 inhibitors significantly reduce the incidence of diabetic retinopathy (OR\u2009[95\n                    <jats:italic>%<\/jats:italic>\n                    CI] = 0.48 [0.28, 0.85],\n                    <jats:italic>p<\/jats:italic>\n                    = 0.01). The coronary heart disease as positive control.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The findings show that HMGCR inhibitors and PCSK9 inhibitors may significantly increase the risk of diabetic microvascular complications. However, NPC1L1 inhibitors may provide protection against diabetic retinopathy.\n                  <\/jats:p>","DOI":"10.1155\/jdr\/3661739","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T02:06:40Z","timestamp":1741745200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Association Between Cholesterol\u2010Lowering Drugs and Diabetic Microvascular Complications: A Drug\u2010Target Mendelian Randomization Study"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3588-4946","authenticated-orcid":false,"given":"Bo","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-2347","authenticated-orcid":false,"given":"Bo","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8060-5314","authenticated-orcid":false,"given":"Qu","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2757-8835","authenticated-orcid":false,"given":"Sicheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4501-0968","authenticated-orcid":false,"given":"Shun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2065-5886","authenticated-orcid":false,"given":"Mengxue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.02.023"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-05964-x"},{"key":"e_1_2_15_3_2","first-page":"936","article-title":"Retinopathy, neuropathy and nephropathy in non-insulin-dependent diabetic patients","volume":"90","author":"Tai T. 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