Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy
Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechani...
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| container_title | The journal of clinical endocrinology and metabolism |
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| creator | Nguyen, My-Le Sachdev, Vandana Burklow, Thomas R Li, Wen Startzell, Megan Auh, Sungyoung Brown, Rebecca J |
| description | Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia. Objective: Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy. Methods: Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N = 27), and 3 to 5 years (N = 23) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance. Results: In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg/dL at baseline, 1 year, 3-5 years, P |
| doi_str_mv | 10.1210/clinem/dgab499 |
| format | Article |
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Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia. Objective: Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy. Methods: Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N = 27), and 3 to 5 years (N = 23) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance. Results: In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg/dL at baseline, 1 year, 3-5 years, P<.0001), A1c (9.5 [+ or -]3.0, 6.5 [+ or -]1.6, 6.5 [+ or -]1.9%, P<.001), and HOMA-IR (34.1 [15.2-43.5], 8.7 [2.4-16.0], 8.9 [2.1-16.4], P<.001). Only HOMA-IR improved in PLD(P<.01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8 [+ or -]1.7, 9.1 [+ or -]1.3, 8.3 [+ or -]1.7 mm, P<.01), and LV mass (140.7 [+ or -]45.9, 128.7 [+ or -]37.9, 110.9 [+ or -]29.1 g, P<.01), and increased septal e' velocity (8.6 [+ or -] 1.7,10.0 [+ or -] 2.1,10.7 [+ or -] 2.4 cm/s, P<.01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e' velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD. Conclusion: Metreleptin attenuated cardiac hypertrophy and improved septal e' velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined. Key Words: Leptin, lipodystrophy, cardiomyopathy, left ventricular hypertrophy]]></description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgab499</identifier><identifier>PMID: 34223895</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adipose tissues ; Cardiac patients ; Care and treatment ; Heart ; Heart enlargement ; Hyperglycemia ; Insulin resistance ; Lipodystrophy ; Online Only ; Triglycerides</subject><ispartof>The journal of clinical endocrinology and metabolism, 2021-11, Vol.106 (11), p.e4327-e4339</ispartof><rights>COPYRIGHT 2021 Oxford University Press</rights><rights>Published by Oxford University Press on behalf of the Endocrine Society 2021. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-b2392731badd8c9bce54bd771255bd21e84020b92bd2af9c17a7b4e5f76972663</citedby><cites>FETCH-LOGICAL-c434t-b2392731badd8c9bce54bd771255bd21e84020b92bd2af9c17a7b4e5f76972663</cites><orcidid>0000-0002-2589-7382</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids></links><search><creatorcontrib>Nguyen, My-Le</creatorcontrib><creatorcontrib>Sachdev, Vandana</creatorcontrib><creatorcontrib>Burklow, Thomas R</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>Startzell, Megan</creatorcontrib><creatorcontrib>Auh, Sungyoung</creatorcontrib><creatorcontrib>Brown, Rebecca J</creatorcontrib><title>Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy</title><title>The journal of clinical endocrinology and metabolism</title><description><![CDATA[Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia. Objective: Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy. Methods: Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N = 27), and 3 to 5 years (N = 23) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance. Results: In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg/dL at baseline, 1 year, 3-5 years, P<.0001), A1c (9.5 [+ or -]3.0, 6.5 [+ or -]1.6, 6.5 [+ or -]1.9%, P<.001), and HOMA-IR (34.1 [15.2-43.5], 8.7 [2.4-16.0], 8.9 [2.1-16.4], P<.001). Only HOMA-IR improved in PLD(P<.01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8 [+ or -]1.7, 9.1 [+ or -]1.3, 8.3 [+ or -]1.7 mm, P<.01), and LV mass (140.7 [+ or -]45.9, 128.7 [+ or -]37.9, 110.9 [+ or -]29.1 g, P<.01), and increased septal e' velocity (8.6 [+ or -] 1.7,10.0 [+ or -] 2.1,10.7 [+ or -] 2.4 cm/s, P<.01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e' velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD. Conclusion: Metreleptin attenuated cardiac hypertrophy and improved septal e' velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined. Key Words: Leptin, lipodystrophy, cardiomyopathy, left ventricular hypertrophy]]></description><subject>Adipose tissues</subject><subject>Cardiac patients</subject><subject>Care and treatment</subject><subject>Heart</subject><subject>Heart enlargement</subject><subject>Hyperglycemia</subject><subject>Insulin resistance</subject><subject>Lipodystrophy</subject><subject>Online Only</subject><subject>Triglycerides</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNptkc2LFDEQxYMo7rh69dzgxUvv5nPSuQjDoLvCgHtQ9BbyUT0T6U7aJCOMf71ZZhCEJYciVb96vOIh9JbgG0IJvnVTiDDf-r2xXKlnaEUUF70kSj5HK4wp6ZWkP67Qq1J-Ykw4F-wlumKcUjYosUIPO1hqiN2mVohHU6F0W5N9MK67Py2Qa07L4dQ14sHUALGW7nuoh-4OImQzhT_gu11Ykj-VM_oavRjNVODNpV6jb58-ft3e97svd5-3m13vOOO1t5QpKhmxxvvBKetAcOulJFQI6ymBgWOKraLtY0bliDTSchCjXLeD1mt2jT6cdZejncG7Zq350UsOs8knnUzQ_09iOOh9-q0HwbCkrAm8vwjk9OsIpeo5FAfTZCKkY9FU8GGNZYMb-u6M7s0EOsQxNUX3iOuNxJRJQQlp1M0TVHse5uBShDG0_lMLLqdSMoz_3BOsH9PV53T1JV32FxgkmaE</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Nguyen, My-Le</creator><creator>Sachdev, Vandana</creator><creator>Burklow, Thomas R</creator><creator>Li, Wen</creator><creator>Startzell, Megan</creator><creator>Auh, Sungyoung</creator><creator>Brown, Rebecca J</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2589-7382</orcidid></search><sort><creationdate>20211101</creationdate><title>Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy</title><author>Nguyen, My-Le ; Sachdev, Vandana ; Burklow, Thomas R ; Li, Wen ; Startzell, Megan ; Auh, Sungyoung ; Brown, Rebecca J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-b2392731badd8c9bce54bd771255bd21e84020b92bd2af9c17a7b4e5f76972663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adipose tissues</topic><topic>Cardiac patients</topic><topic>Care and treatment</topic><topic>Heart</topic><topic>Heart enlargement</topic><topic>Hyperglycemia</topic><topic>Insulin resistance</topic><topic>Lipodystrophy</topic><topic>Online Only</topic><topic>Triglycerides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nguyen, My-Le</creatorcontrib><creatorcontrib>Sachdev, Vandana</creatorcontrib><creatorcontrib>Burklow, Thomas R</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>Startzell, Megan</creatorcontrib><creatorcontrib>Auh, Sungyoung</creatorcontrib><creatorcontrib>Brown, Rebecca J</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nguyen, My-Le</au><au>Sachdev, Vandana</au><au>Burklow, Thomas R</au><au>Li, Wen</au><au>Startzell, Megan</au><au>Auh, Sungyoung</au><au>Brown, Rebecca J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><date>2021-11-01</date><risdate>2021</risdate><volume>106</volume><issue>11</issue><spage>e4327</spage><epage>e4339</epage><pages>e4327-e4339</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract><![CDATA[Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia. Objective: Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy. Methods: Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N = 27), and 3 to 5 years (N = 23) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance. Results: In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg/dL at baseline, 1 year, 3-5 years, P<.0001), A1c (9.5 [+ or -]3.0, 6.5 [+ or -]1.6, 6.5 [+ or -]1.9%, P<.001), and HOMA-IR (34.1 [15.2-43.5], 8.7 [2.4-16.0], 8.9 [2.1-16.4], P<.001). Only HOMA-IR improved in PLD(P<.01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8 [+ or -]1.7, 9.1 [+ or -]1.3, 8.3 [+ or -]1.7 mm, P<.01), and LV mass (140.7 [+ or -]45.9, 128.7 [+ or -]37.9, 110.9 [+ or -]29.1 g, P<.01), and increased septal e' velocity (8.6 [+ or -] 1.7,10.0 [+ or -] 2.1,10.7 [+ or -] 2.4 cm/s, P<.01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e' velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD. Conclusion: Metreleptin attenuated cardiac hypertrophy and improved septal e' velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined. Key Words: Leptin, lipodystrophy, cardiomyopathy, left ventricular hypertrophy]]></abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>34223895</pmid><doi>10.1210/clinem/dgab499</doi><orcidid>https://orcid.org/0000-0002-2589-7382</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adipose tissues Cardiac patients Care and treatment Heart Heart enlargement Hyperglycemia Insulin resistance Lipodystrophy Online Only Triglycerides |
| title | Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy |
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