Steven Grinspoon

Steven Grinspoon is an American physician and a Professor of Medicine at Harvard Medical School, Chief of the Massachusetts General Hospital’s (MGH) Metabolism Unit, and Director of the Nutrition and 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 the physiological consequences of fat distribution on cardiovascular disease and inflammation. In 2015, he became the Principal Investigator of the NIH-funded Nutrition Obesity Research Center at Harvard.

Education and early life

Grinspoon is the son of Eileen Grinspoon and real estate developer Harold Grinspoon. Grinspoon graduated from Cornell University in 1983. He attended the University of Rochester School of Medicine, graduating in 1988. He completed his medical residency and served as Chief Resident at Columbia Presbyterian from 1988 to 1992. Grinspoon completed his Endocrinology Fellowship at Massachusetts General Hospital from 1992 to 1995.

Research and awards

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, Grinspoon led a series of studies culminating in a NEJM paper demonstrating that Tesamorelin reduced visceral fat by 20% and reduced triglyceride while improving adiponectin. This work led to FDA approval of Tesamorelin as the only such approved drug for HIV lipodystrophy and the 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. Subsequent work demonstrated significant effects to stimulate hepatic oxidative pathways and reduce inflammatory pathways in gene set enrichment studies. Grinspoon was granted a US Patent entitled “GHRH or Analogues Thereof for the Use in Treatment of Hepatic Disease” for this work. Tesamorelin was also studied in individuals with generalized obesity, where it was observed to reduce cIMT, inflammatory markers, lipids, and visceral adiposity.

A significant area of focus in Grinspoon’s research has been investigating the mechanisms and strategies for addressing cardiovascular disease (CVD) in HIV. He led an American Heart Association (AHA)-sponsored State of the Science Symposium on CVD in HIV, which concluded with a call for improved understanding and treatment strategies for CVD in HIV. His work began with epidemiologic studies that demonstrated increased myocardial infarction rates among HIV patients, as published in the JCEM.

This data led to further mechanistic studies, which identified a higher prevalence of plaque, particularly noncalcified, lipid-rich plaque. Grinspoon utilized FDG PET imaging to demonstrate, for the first time, significant arterial inflammation in asymptomatic, low-traditional risk HIV patients. This study, published in JAMA, compared HIV patients with Framingham risk-matched controls and non-HIV patients with known CVD. Notably, increased arterial inflammation was strongly associated with elevated markers of immune activation.

Recently, Grinspoon proposed and successfully applied Tilmanocept as a CD206-specific imaging agent for arterial inflammation in HIV, with findings published in JID. Additionally, he conducted studies that characterized coronary plaque morphology in HIV patients, revealing an increased prevalence of high-risk plaques with low attenuation and positive remodeling—features that make them more prone to rupture.

His findings suggested that statin therapy could not only address traditional risk factors like low-density lipoprotein (LDL) but also mitigate immune activation-driven noncalcified high-risk plaque in HIV patients. A 2023 study published in the Lancet HIV demonstrated that statin treatment reduced high-risk plaque volume and improved coronary lesion morphology in individuals with HIV.

Recognizing the significance of these findings, Grinspoon has been leading the REPRIEVE trial, a global primary prevention study conducted across 12 countries since 2013. He delivered the plenary lecture on this topic at CROI 2015. The REPRIEVE trial was recently halted early by its Data Safety Monitoring Board due to a robust efficacy signal, showing that statin therapy reduced major adverse cardiovascular events—including heart attacks, strokes, and cardiovascular deaths—by 35% over five years compared to placebo. These findings were recently published in the New England Journal of Medicine and presented by Grinspoon at the International AIDS Society 2023 meeting in Brisbane. The study has been featured in various news outlets and scientific discussions.

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.

Awards

Grinspoon was elected to the American Society for Clinical Investigation in 2003.

In 2016, he received the Gerald D. Aurbach Laureate Award for Outstanding Translational Research from the Endocrine Society.

Personal life

Grinspoon married Winifred Ann Sandler in 1988.

Selected works

• Grinspoon, Steven K. (April 2003). "Weight loss and wasting in patients infected with human immunodeficiency virus.” Clinical Infectious Diseases 36 (69-78).
• Grinspoon, Steven K. (19 June 2008). “Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS”.Circulation (journal) 18
• Grinspoon, Steven K. ;Lake, Jordan, Stanley, Takara; Apovian, Caroline; Brown, Todd. (15 May 2017). “Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection”. Clinical Infectious Diseases 64 (1422–1429).

• Grinspoon, Steven K; Brown, Todd T. (2020) Williams Textbook of Endocrinology:”Endocrinology of HIV/AIDS”. Elsevier.

• Grinspoon, Steven K; Stlanley, Takara L. (January 2022) Oxford Textbook of Endocrinology and Diabetes: “Abnormalities in HIV Infection”. Oxford University Press.

• Grinspoon, Steven K; Zanni, Markella V.; Fitchenbaum, Carl J. (July 23, 2023) New England Journal of Medicine: “Pitavastatin to Prevent Cardiovascular Disease in HIV Infection”. Massachusetts Medical Society.

References

External links

• MGH Metabolism Unit Website
• REPRIEVE Trial Website
• Nutrition Obesity Research Center at Harvard Website