Steven Grinspoon

Add links
From Wikipedia, the free encyclopedia
Steven Grinspoon

Steven Grinspoon is an American physician who is a Professor of Medicine at Harvard Medical School, Chief of the Massachusetts General Hospital (MGH) Metabolism Unit, and Director of the Nutrition Obesity Research Center at Harvard. In addition, he is the MGH Endowed Chair in Neuroendocrinology and Metabolism. His work investigates the neuroendocrine regulation of body composition, and physiologic consequences of fat distribution on cardiovascular disease and inflammation.[1] He has investigated the effects of reduced growth hormone on metabolic dysregulation in obesity and was the first to propose the use of a Growth Hormone-releasing Hormone (GHRH) analogue to increase endogenous GH secretion on lipodystrophy and generalized obesity, which led to the FDA approval of Tesamorelin for excess visceral fat accumulation in HIV-infected patients.[2] This work has now been extended to show effects on non-alcoholic fatty liver disease (NAFLD).[3] More recently, his research focuses on the inflammatory mechanisms by which ectopic fat and other metabolic perturbations contribute to HIV-Cardiovascular disease (CVD), and in this regard, he led the AHA State of the Science Conference on CVD in HIV. Additionally, he is leading the multicenter REPRIEVE study, the first study of a primary prevention strategy for CVD in people living with HIV.[4] He has also investigated increased Renin-Angiotensin-Aldosterone System (RAAS) activation and immune activation in relationship to visceral fat accumulation, and the mechanisms of subcutaneous adipose dysfunction involving DICER. Grinspoon has served on the Harvard faculty since 1995 and has been selected by the American Society for Clinical Investigation and the Association of American Physicians for his scientific contributions.[5][6][7] He received the American Federation of Medical Research Investigator of the Year Award in 2005 and the Edward H. Ahrens Jr. Award for Patient Oriented Research in 2014 as well as the Endocrine Society Laureate Award for Translational Research in 2016.[8][9][10] He has published over 330 articles and mentored over 40 trainees in his career. He was elected as a Member of the American Clinical and Climatological Association for his achievements in 2017.[11] His work demonstrating the effects of Tesamorelin to reduce hepatic fat and fibrosis progression in NAFLD, published in Lancet HIV, was a finalist for the Clinical Research Forum’s top 10 Clinical Research Achievement Awards in 2020.[12][13] In 2015, he became the Principal Investigator of the NIH-funded Nutrition Obesity Research Center at Harvard.[14]

Publications[edit]

Grinspoon has published 309 original research articles, and over 50 review papers in his field. He has authored key Chapters in the Williams Textbook of Endocrinology and The Oxford textbook of Endocrinology on the endocrine manifestation of HIV/AIDS.[15][16] He has served on the Weight Loss and Wasting Working Group Expert Panel on National HIV/AIDS to develop Nutrition Guidelines for the Department of Health and Human Services and developed guidelines for the Nutritional Assessment of HIV-infected Patients in work commissioned by the NIH and WHO.[17] He has contributed to guidelines on the prevention and management of cardiovascular disease in HIV, Chairing the AHA State of the Science Conference on CVD Risk in HIV in 2008, published in Circulation and the NIH sponsored symposium on the Review and Recognition of Obesity in HIV in 2017, published in Clinical Infectious Diseases[18]. He has also participated in the writing group of guidelines for the International AIDS Society-USA Management of Metabolic Complications Associated with Antiretroviral Therapy for HIV-1 infection.[19] He has served on the Advisory Boards of JCEM, JAIDS AIDS, and Nature Reviews Endocrinology, and the Journal of Clinical Investigation.[citation needed]

Education[edit]

Grinspoon graduated from Cornell University in 1983, attended the University of Rochester School of Medicine, graduating in 1988, and was awarded AOA Alumni Award from the medical school in 2006.[citation needed] He did his medical residency and Chief Residency at Columbia Presbyterian from 1988 to 1992 and his Endocrinology Fellowship at Massachusetts General Hospital from 1992 to 1995.[6]

Research and awards[edit]

Grinspoon’s primary research focus has been to investigate the effects of augmenting endogenous GH pulsatility on visceral fat in lipodystrophic patients with abdominal fat accumulation and nonalcoholic fatty liver disease. This work was initiated by an observation of reduced GH secretion in HIV patients with lipodystrophy. Subsequent studies examined the mechanisms and demonstrated reduced area under the curve per peak, but maintenance of the GH pulse generator in such patients. Reasoning that augmentation of GH pulsatility might reduce visceral fat, because of its potent effects to oxidize adipose tissue, Grinspoon led a series of studies culminating in a NEJM paper demonstrating that Tesamorelin, a GHRH1-44 secretagogue, reduced visceral fat by 20% and reduced triglyceride, while improving adiponectin.[9] This work led to FDA approval of Tesamorelin as the only such approved drug for HIV lipodystrophy and first in class molecule. Subsequent studies, published in JAMA and Lancet HIV, demonstrated that Tesamorelin reduced hepatic steatosis as well, the first drug to demonstrate a significant effect among patients with HIV lipodystrophy.[20][21][22] Subsequent work demonstrated significant effects to stimulate hepatic oxidative pathways and reduce inflammatory pathways in gene set enrichment studies.[11] Grinspoon was granted a US Patent entitled “GHRH or Analogues thereof for the Use in Treatment of Hepatic Disease” for this work.[12] Tesamorelin was also investigated in generalized obesity and showed significant effects to reduce cIMT, inflammatory markers, lipids and visceral adiposity.[13]

A second and related focus of Grinspoon’s work has been to investigate the mechanisms and strategies for CVD in HIV.  In this regard, he led an AHA sponsored State of the Science Symposium on CVD in HIV. The conclusions from this conference called for a better understanding and treatment strategies of CVD in HIV. This work began with epidemiologic studies demonstrating increased myocardial infarction rates in HIV patients in the JCEM.[14] This data was followed by a series of mechanistic studies demonstrating increased prevalence of plaque, particularly noncalcified, lipid rich, plaque. Grinspoon used FDG PET to demonstrate for the first time significant arterial inflammation in asymptomatic low traditional risk HIV patients, compared to Framingham risk matched control subjects, as well as non HIV patients with known CVD, published in JAMA.[15] Of note, increased arterial inflammation was most significantly associated with increased markers of immune activation. He also recently proposed the first use of tilmanocept as a CD206 specific imaging agent for arterial inflammation, with success in HIV published in JID.[16] This work was followed by studies in HIV patients in which he phenotyped the morphological characteristics of coronary plaque in HIV patients, demonstrating an increased prevalence of high risk plaque with low attenuation and positive remodeling, more vulnerable to rupture.[17] His studies suggested that treatment with a statin might uniquely target both traditional risk factors including low-density lipoprotein (LDL) but also increased immune activation indices driving atypical noncalcified high risk plaque in this population. This work culminated in a recent paper in Lancet HIV, in which he showed for the first time that a statin can significantly reduce high risk plaque volume as well as improve the high-risk morphological features in coronary lesions in HIV.[18] In recognition of this work, he has led the REPRIEVE trial, a global primary prevention study performed in 12 countries, since 2013 and gave the plenary lecture at CROI 2015 on this topic.[19][23] The REPRIEVE trial was recently closed early by its Data Safety Monitoring Board for a robust efficacy signal, demonstrating that a statin strategy reduced major adverse cardiovascular event (primary heart attacks, strokes, and cardiovascular death) by 35% over 5 years, compared to placebo. This trial was recently published in the New England Journal of Medicine and the data presented by Grinspoon at the International AIDS Society 2023 meeting in Brisbane and featured in news articles and podcasts.[24][25][26][27][28]

Grinspoon has worked to understand the mechanism, and treatment strategies for metabolic dysregulation in HIV, and was among the first to assess metformin and rosiglitazone to reverse insulin resistance and increase adipogenesis in this population. He also recognized reduced DICER as a factor that may contribute to dysfunctional adipose tissue in HIV.[9][20][21]

Awards[edit]

Grinspoon was elected to the American Society of Clinical Investigation (ASCI) in 2003 and the Honor Society for Humanism in Medicine for the Arnold P. Gold Foundation in 2004. He received the Outstanding Investigator Award from the American Federation for Medical Research in 2005 and was honored with the Pfizer Visiting Professorship at UC Davis in 2004, the Frank H. Tyler Honorary Endowed Lectureship at the University of Utah in 2008, the Dorothy M. Kahkonen Lectureship at the Henry Ford Health System in 2009, the Johnson Maguire Visiting Professorship at the University of Cincinnati in 2015 and the Michael O. Thorner Distinguished Lectureship in Endocrinology from the University of Virginia in 2019. He was named the Alpha Omega Alpha Alumni of the year Awardee at the University of Rochester in 2006 and elected to the Association of American Physicians in 2011. In 2014, he received the Edward H. Ahrens Award for Patient Oriented Clinical Research from the Association of Clinical and Translational Science (ACTS) and the American Medical Federation for Medical Research (AMFAR). In 2016 He received the Gerald Aurbach Laureate Award[22] for Outstanding Translational Research from the Endocrine Society. In 2017 he was elected to the American Clinical and Climatological Association. Grinspoon received an Albert Nelson Lifetime Achievement Award from Who’s Who in America in 2017 and his research on the use of Tesamorelin for fatty liver disease in the Lancet HIV was named as a finalist to the Top 10 Clinical Research Achievement Awards[29] in 2020. In 2023, he was named the 2023 Berson-Yalow Lecturer for the Mt. Sinai Department of Medicine.

Key discoveries[edit]

  • Efficacy of Tesamorelin to reduce visceral adiposity 2007 (NEJM)[30]
  • Efficacy of Tesamorelin to reduce liver fat 2014 (JAMA)[9]
  • Efficacy of Tesamorelin to prevent liver fibrosis progression in 2019 (Lancet HIV)[10]
  • Demonstration of Tesamorelin effects on key hepatic metabolic pathways in 2020 (JCI Insight)[11]
  • Demonstration of increased arterial inflammation in HIV in 2012 (JAMA)[31]
  • Identification of key genes and proteins leading to dysfunctional subcutaneous adipose tissue in HIV Lipodystrophy 2021 (JCI Insight)
  • First use of macrophage specific imaging agent to identify plaque cardiovascular imaging (JID 2021)

Selected Talks[edit]

Title Date Meeting
2023
Timelines for Study Closure, Publications and Data Availability June 13 AIDS Clinical Trials Group (ACTG) Plenary 2023
The REPRIEVE Trial: Developing a Cardiovascular Disease Prevention Strategy for People Living with HIV July 24 International AIDS Society (IAS) 2023 Symposium
Cardiovascular Disease Risk Reduction in HIV Infection: The REPRIEVE Trial August 24 6th Closed Scientific Expert Meeting of the Triglyceride Forum Editorial Board
Update on the REPRIEVE Trial to Prevent Cardiovascular Events in People with HIV September 6 Viral Infections & Inflammation Workshop
The REPRIEVE Trial: Consideration for People with HIV in Sub Saharan Africa October 2 President's Emergency Plan for AIDS Relief (PEPFAR) Scientific Advisory Board Meeting
Cardiovascular Disease Prevention in Patients with HIV: The REPRIEVE Trial October 27 International Antiviral Society-USA Webinar
Reducing Cardiovascular Disease in People with HIV: Rationale and Results of the REPRIEVE Trial October 4 Beth Israel Deaconess Medical Center Endocrine Grand Rounds
Cardiovascular Disease Reduction in People with HIV: Implications of the REPRIEVE Trial   November 8 National Center for AIDS Research (CFAR) Meeting
What has the REPRIEVE Trial Taught Us November 24 7th Edition of the Aging in HIV Workshop
Pitavastatin to Prevent Cardiovascular Disease in HIV Infection November 29 Boston University Cardiology Grand Rounds
Results from the REPRIEVE Trial: Implications for the Clinical Care of Patients with HIV December 3 Ryan White HIV/AIDS Program (RWHAP) Clinical Conference

References[edit]

  1. ^ Achermann, John C.; et al. (2016-01-01). "Contributors". Williams Textbook of Endocrinology: v–xiv. doi:10.1016/B978-0-323-29738-7.00047-2. ISBN 9780323297387.
  2. ^ Wass, John A. H.; Stewart, Paul M. (2011-07-28). Oxford Textbook of Endocrinology and Diabetes. OUP Oxford. ISBN 978-0-19-923529-2.
  3. ^ "Nutrient requirements for people living with HIV/AIDS: Report of a technical consultation" (PDF). World Health Organization. Archived (PDF) from the original on June 24, 2006. Retrieved 7 April 2021.
  4. ^ Lake JE, Stanley TL, Apovian CM, Bhasin S, Brown TT, Capeau J, Currier JS, Dube MP, Falutz J, Grinspoon SK, Guaraldi G, Martinez E, McComsey GA, Sattler FR, Erlandson KM. Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection. Clin Infect Dis. 2017 May 15;64(10):1422-1429. doi:10.1093/cid/cix178 Erratum in: Clin Infect Dis. 2017 Oct 15;65(8):1431-1433. PMID 28329372; PMCID: PMC5411395.
  5. ^ Schambelan M, Benson CA, Carr A, Currier JS, Dubé MP, Gerber JG, Grinspoon SK, Grunfeld C, Kotler DP, Mulligan K, Powderly WG, Saag MS; International AIDS Society-USA. Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International AIDS Society-USA panel. J Acquir Immune Defic Syndr. 2002 Nov 1;31(3):257-75. doi:10.1097/00126334-200211010-00001 PMID 12439201.
  6. ^ a b "Steven Grinspoon, MD - Neuroendocrinology". Massachusetts General Hospital. Retrieved 2021-04-07.
  7. ^ Falutz, Julian; Allas, Soraya; Blot, Koenraad; Potvin, Diane; Kotler, Donald; Somero, Michael; Berger, Daniel; Brown, Stephen; Richmond, Gary; Fessel, Jeffrey; Turner, Ralph (2007-12-06). "Metabolic Effects of a Growth Hormone–Releasing Factor in Patients with HIV". New England Journal of Medicine. 357 (23): 2359–2370. doi:10.1056/NEJMoa072375. ISSN 0028-4793. PMID 18057338.
  8. ^ Lo J, You SM, Canavan B, Liebau J, Beltrani G, Koutkia P, Hemphill L, Lee H, Grinspoon S. Low-dose physiological growth hormone in patients with HIV and abdominal fat accumulation: a randomized controlled trial. JAMA. 2008 Aug 6;300(5):509-19. doi:10.1001/jama.300.5.509 PMID 18677023; PMCID: PMC2532757.
  9. ^ a b c d Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014 Jul 23-30;312(4):380-9. doi:10.1001/jama.2014.8334 PMID 25038357; PMCID: PMC4363137.
  10. ^ a b Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019 Dec;6(12):e821-e830. doi:10.1016/S2352-3018(19)30338-8 Epub 2019 Oct 11. PMID 31611038; PMCID: PMC6981288.
  11. ^ a b c Fourman LT, Billingsley JM, Agyapong G, Ho Sui SJ, Feldpausch MN, Purdy J, Zheng I, Pan CS, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Stanley TL, Chung RT, Grinspoon SK. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020 Aug 20;5(16):e140134. doi:10.1172/jci.insight.140134 PMID 32701508; PMCID: PMC7455119.
  12. ^ a b US 10946073, Grinspoon, Steven K., "GHRH or analogues thereof for use in treatment of hepatic disease", published 2021-03-16, assigned to Massachusetts General Hospital 
  13. ^ a b Makimura H, Feldpausch MN, Rope AM, Hemphill LC, Torriani M, Lee H, Grinspoon SK. Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial. J Clin Endocrinol Metab. 2012 Dec;97(12):4769-79. doi:10.1210/jc.2012-2794 Epub 2012 Sep 26. PMID 23015655; PMCID: PMC3513535.
  14. ^ a b Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12. doi:10.1210/jc.2006-2190 Epub 2007 Apr 24. PMID 17456578; PMCID: PMC2763385.
  15. ^ a b Subramanian, Sharath; Tawakol, Ahmed; Burdo, Tricia H.; Abbara, Suhny; Wei, Jeffrey; Vijayakumar, Jayanthi; Corsini, Erin; Abdelbaky, Amr; Zanni, Markella V.; Hoffmann, Udo; Williams, Kenneth C. (2012-07-25). "Arterial Inflammation in Patients With HIV". JAMA. 308 (4): 379–386. doi:10.1001/jama.2012.6698. ISSN 0098-7484. PMC 3724172. PMID 22820791.
  16. ^ a b Zanni MV, Toribio M, Wilks MQ, Lu MT, Burdo TH, Walker J, Autissier P, Foldyna B, Stone L, Martin A, Cope F, Abbruzzese B, Brady T, Hoffmann U, Williams KC, El-Fakhri G, Grinspoon SK. Application of a Novel CD206+ Macrophage-Specific Arterial Imaging Strategy in HIV-Infected Individuals. J Infect Dis. 2017 Apr 15;215(8):1264-1269. doi:10.1093/infdis/jix095 PMID 28204544; PMCID: PMC5853590.
  17. ^ a b Zanni MV, Abbara S, Lo J, Wai B, Hark D, Marmarelis E, Grinspoon SK. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS. 2013 May 15;27(8):1263-72. doi:10.1097/QAD.0b013e32835eca9b PMID 23324657; PMCID: PMC3740057.
  18. ^ a b Lo J, Lu MT, Ihenachor EJ, Wei J, Looby SE, Fitch KV, Oh J, Zimmerman CO, Hwang J, Abbara S, Plutzky J, Robbins G, Tawakol A, Hoffmann U, Grinspoon SK. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2015 Feb;2(2):e52-63. doi:10.1016/S2352-3018(14)00032-0 Epub 2015 Jan 9. PMID 26424461; PMCID: PMC4820828.
  19. ^ a b "Steven K. Grinspoon, MD". REPRIEVE Trial. Retrieved 2021-04-07.
  20. ^ a b Hadigan, Colleen; Yawetz, Sigal; Thomas, Abraham; Havers, Fiona; Sax, Paul E.; Grinspoon, Steven (2004-05-18). "Metabolic Effects of Rosiglitazone in HIV Lipodystrophy". Annals of Internal Medicine. 140 (10): 786–794. doi:10.7326/0003-4819-140-10-200405180-00008. ISSN 0003-4819. PMID 15148065. S2CID 53089714.
  21. ^ a b Torriani M, Srinivasa S, Fitch KV, Thomou T, Wong K, Petrow E, Kahn CR, Cypess AM, Grinspoon SK. Dysfunctional Subcutaneous Fat With Reduced Dicer and Brown Adipose Tissue Gene Expression in HIV-Infected Patients. J Clin Endocrinol Metab. 2016 Mar;101(3):1225-34. doi:10.1210/jc.2015-3993 Epub 2016 Jan 12. PMID 26756119; PMCID: PMC4803164.
  22. ^ a b Newman, Mark (2016-01-22). "Meet the 2016 Laureate Award Winners: Steven Grinspoon, MD". Endocrine News. Retrieved 2022-10-17.
  23. ^ "Cardiovascular Disease in HIV Patients: An Emerging Paradigm and Call to Action". CROI Conference. 24 February 2015. Retrieved 2021-04-07.
  24. ^ "Daily Statin Medication Reduces Risk of Major Cardiovascular Events by More Than One-Third in People Living with HIV". Massachusetts General Hospital. Retrieved 2023-11-22.
  25. ^ "Daily statin reduces heart disease risk among adults living with HIV". National Institutes of Health (NIH). 2023-07-24. Retrieved 2023-11-22.
  26. ^ "Preventing HIV's Collateral Cardiovascular Damage: ITT Episode 15". New England Journal of Medicine. 389 (7): e11. 2023-08-17. doi:10.1056/NEJMp2307347. ISSN 0028-4793.
  27. ^ Ryan, Benjamin (2023-09-10). "For 'Silver Tsunami' With H.I.V., New Hope for Healthy Aging". The New York Times. ISSN 0362-4331. Retrieved 2023-11-22.
  28. ^ "For people with HIV, statins show 35 percent drop in heart attack risk". Washington Post. 2023-09-29. ISSN 0190-8286. Retrieved 2023-11-22.
  29. ^ "2020 TOP 10 FINALISTS".
  30. ^ Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007 Dec 6;357(23):2359-70. doi:10.1056/NEJMoa072375 PMID 18057338.
  31. ^ Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, Williams KC, Lo J, Grinspoon SK. Arterial inflammation in patients with HIV. JAMA. 2012 Jul 25;308(4):379-86. doi:10.1001/jama.2012.6698 PMID 22820791; PMCID: PMC3724172.

External links[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Steven_Grinspoon&oldid=1206174477"