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Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies
The metabolically active retina obtains essential lipids by endogenous biosynthesis and from the systemic circulation. Clinical studies provide limited and sometimes conflicting evidence as to the relationships between circulating lipid levels and the development and progression of diabetic retinopa...
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| Published in: | Diabetologia 2022-04, Vol.65 (4), p.587-603 |
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| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c474t-cd8f3a5912f65d5cda82128de2014a4f5eb275c6ff347ced2378788ea6f7fa783 |
| container_end_page | 603 |
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| container_title | Diabetologia |
| container_volume | 65 |
| creator | Jenkins, Alicia J. Grant, Maria B. Busik, Julia V. |
| description | The metabolically active retina obtains essential lipids by endogenous biosynthesis and from the systemic circulation. Clinical studies provide limited and sometimes conflicting evidence as to the relationships between circulating lipid levels and the development and progression of diabetic retinopathy in people with diabetes. Cardiovascular-system-focused clinical trials that also evaluated some retinal outcomes demonstrate the potential protective power of lipid-lowering therapies in diabetic retinopathy and some trials with ocular primary endpoints are in progress. Although triacylglycerol-lowering therapies with fibrates afforded some protection against diabetic retinopathy, the effect was independent of changes in traditional blood lipid classes. While systemic LDL-cholesterol lowering with statins did not afford protection against diabetic retinopathy in most clinical trials, and none of the trials focused on retinopathy as the main outcome, data from very large database studies suggest the possible effectiveness of statins. Potential challenges in these studies are discussed, including lipid-independent effects of fibrates and statins, modified lipoproteins and retinal-specific effects of lipid-lowering drugs. Dysregulation of retinal-specific cholesterol metabolism leading to retinal cholesterol accumulation and potential formation of cholesterol crystals are also addressed.
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| doi_str_mv | 10.1007/s00125-022-05655-z |
| format | article |
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Graphical abstract</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-022-05655-z</identifier><identifier>PMID: 35149880</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Cholesterol ; Clinical trials ; Crystals ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus - drug therapy ; Diabetic retinopathy ; Diabetic Retinopathy - drug therapy ; Fibric Acids - therapeutic use ; Human Physiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Internal Medicine ; Lipid metabolism ; Lipids ; Lipids - chemistry ; Lipoproteins ; Low density lipoprotein ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolic disorders ; Retina ; Retina - physiopathology ; Retinopathy ; Review ; Statins</subject><ispartof>Diabetologia, 2022-04, Vol.65 (4), p.587-603</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-cd8f3a5912f65d5cda82128de2014a4f5eb275c6ff347ced2378788ea6f7fa783</citedby><cites>FETCH-LOGICAL-c474t-cd8f3a5912f65d5cda82128de2014a4f5eb275c6ff347ced2378788ea6f7fa783</cites><orcidid>0000-0003-3453-7124</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35149880$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jenkins, Alicia J.</creatorcontrib><creatorcontrib>Grant, Maria B.</creatorcontrib><creatorcontrib>Busik, Julia V.</creatorcontrib><title>Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>The metabolically active retina obtains essential lipids by endogenous biosynthesis and from the systemic circulation. Clinical studies provide limited and sometimes conflicting evidence as to the relationships between circulating lipid levels and the development and progression of diabetic retinopathy in people with diabetes. Cardiovascular-system-focused clinical trials that also evaluated some retinal outcomes demonstrate the potential protective power of lipid-lowering therapies in diabetic retinopathy and some trials with ocular primary endpoints are in progress. Although triacylglycerol-lowering therapies with fibrates afforded some protection against diabetic retinopathy, the effect was independent of changes in traditional blood lipid classes. While systemic LDL-cholesterol lowering with statins did not afford protection against diabetic retinopathy in most clinical trials, and none of the trials focused on retinopathy as the main outcome, data from very large database studies suggest the possible effectiveness of statins. Potential challenges in these studies are discussed, including lipid-independent effects of fibrates and statins, modified lipoproteins and retinal-specific effects of lipid-lowering drugs. Dysregulation of retinal-specific cholesterol metabolism leading to retinal cholesterol accumulation and potential formation of cholesterol crystals are also addressed.
Graphical abstract</description><subject>Cholesterol</subject><subject>Clinical trials</subject><subject>Crystals</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus - drug therapy</subject><subject>Diabetic retinopathy</subject><subject>Diabetic Retinopathy - drug therapy</subject><subject>Fibric Acids - therapeutic use</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Internal Medicine</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Lipids - chemistry</subject><subject>Lipoproteins</subject><subject>Low density lipoprotein</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolic disorders</subject><subject>Retina</subject><subject>Retina - physiopathology</subject><subject>Retinopathy</subject><subject>Review</subject><subject>Statins</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kU2LFDEQhoMo7rj6BzxIwIsHW_PZSXsQZPELBrwoeAuZpLKTJdNpk56V2X_hPza9s64fBy8JqXrqrUq9CD2m5AUlRL2shFAmO8JYR2QvZXd1B62o4O0pmL6LVku-o7r_eoIe1HpBCOFS9PfRCZdUDFqTFfqxjlP09TneHiYoBUICN8dLwK4c6mxTiiNgD1Ouca7Yjh77aDcwR4dLO8c82Xl7eIWnPMM4R5twbXWwa_kFvmZs6uoELoYWhBBaA5wDTkvjLuXvUOJ4juctFDtFqA_RvWBThUc39yn68u7t57MP3frT-49nb9adE0rMnfM6cCsHykIvvXTeakaZ9sAIFVYECRumpOtD4EI58IwrrbQG2wcVrNL8FL0-6k77zQ68a-MXm8xU4s6Wg8k2mr8zY9ya83xpBq6U5H0TeHYjUPK3PdTZ7GJ1kJIdIe-rYT3TbFBDzxr69B_0Iu9LW8xCccm5Fkw2ih0pV3KtzYvbYSgxi-Pm6Lhpjptrx81VK3ry5zduS35Z3AB-BOq0LBrK797_kf0JA4K8tw</recordid><startdate>20220401</startdate><enddate>20220401</enddate><creator>Jenkins, Alicia J.</creator><creator>Grant, Maria B.</creator><creator>Busik, Julia V.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3453-7124</orcidid></search><sort><creationdate>20220401</creationdate><title>Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies</title><author>Jenkins, Alicia J. ; Grant, Maria B. ; Busik, Julia V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-cd8f3a5912f65d5cda82128de2014a4f5eb275c6ff347ced2378788ea6f7fa783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Cholesterol</topic><topic>Clinical trials</topic><topic>Crystals</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus - drug therapy</topic><topic>Diabetic retinopathy</topic><topic>Diabetic Retinopathy - drug therapy</topic><topic>Fibric Acids - therapeutic use</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Internal Medicine</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Lipids - chemistry</topic><topic>Lipoproteins</topic><topic>Low density lipoprotein</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolic disorders</topic><topic>Retina</topic><topic>Retina - physiopathology</topic><topic>Retinopathy</topic><topic>Review</topic><topic>Statins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jenkins, Alicia J.</creatorcontrib><creatorcontrib>Grant, Maria B.</creatorcontrib><creatorcontrib>Busik, Julia V.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jenkins, Alicia J.</au><au>Grant, Maria B.</au><au>Busik, Julia V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>65</volume><issue>4</issue><spage>587</spage><epage>603</epage><pages>587-603</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>The metabolically active retina obtains essential lipids by endogenous biosynthesis and from the systemic circulation. Clinical studies provide limited and sometimes conflicting evidence as to the relationships between circulating lipid levels and the development and progression of diabetic retinopathy in people with diabetes. Cardiovascular-system-focused clinical trials that also evaluated some retinal outcomes demonstrate the potential protective power of lipid-lowering therapies in diabetic retinopathy and some trials with ocular primary endpoints are in progress. Although triacylglycerol-lowering therapies with fibrates afforded some protection against diabetic retinopathy, the effect was independent of changes in traditional blood lipid classes. While systemic LDL-cholesterol lowering with statins did not afford protection against diabetic retinopathy in most clinical trials, and none of the trials focused on retinopathy as the main outcome, data from very large database studies suggest the possible effectiveness of statins. Potential challenges in these studies are discussed, including lipid-independent effects of fibrates and statins, modified lipoproteins and retinal-specific effects of lipid-lowering drugs. Dysregulation of retinal-specific cholesterol metabolism leading to retinal cholesterol accumulation and potential formation of cholesterol crystals are also addressed.
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| ispartof | Diabetologia, 2022-04, Vol.65 (4), p.587-603 |
| issn | 0012-186X 1432-0428 |
| language | eng |
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| source | Springer Nature |
| subjects | Cholesterol Clinical trials Crystals Diabetes Diabetes mellitus Diabetes Mellitus - drug therapy Diabetic retinopathy Diabetic Retinopathy - drug therapy Fibric Acids - therapeutic use Human Physiology Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Internal Medicine Lipid metabolism Lipids Lipids - chemistry Lipoproteins Low density lipoprotein Medicine Medicine & Public Health Metabolic Diseases Metabolic disorders Retina Retina - physiopathology Retinopathy Review Statins |
| title | Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies |
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