Tuesday, October 5, 2010

Research of Takara Stanley, MD

Takara Stanley, MD, Pediatric Endocrine and Neuroendocrine Units, Instructor in Pediatrics, Harvard Medical School.

My general research interest is the interrelationship between body fat distribution, pituitary hormone dynamics, and metabolic abnormalities such as insulin resistance and dyslipidemia.  Working in the MGH Program in Nutritional Metabolism under the mentorship of Dr. Steven Grinspoon, I am doing clinical research focused on HIV-infected adults, who often experience increased visceral fat and decreased extremity fat after initiation of antiretroviral therapy.  These body composition changes may be accompanied by metabolic and endocrine abnormalities, including decreased growth hormone (GH) secretion, impaired glucose tolerance, dyslipidemia, and increased subclinical atherosclerosis.  The consequences of these changes are significant, as HIV-infected individuals have roughly a 2-fold risk of myocardial infarction compared to the non-infected population and increasingly are faced with metabolic comorbidities such as Type 2 diabetes and hypercholesterolemia.  Previous work in my group has demonstrated that decreased GH secretion is strongly associated with visceral fat accumulation and dyslipidemia, and treatment aimed at increasing GH may be beneficial to reduce visceral fat and improve lipids.  I am currently investigating the effects of a GH releasing hormone (GHRH) analogue on endogenous GH secretion and insulin sensitivity in this population.  In the upcoming months we hope to begin investigating the effects of GHRH on ectopic fat accumulation in liver and muscle as well as the effects on markers of subclinical inflammation and endothelial function.  Recently I have been fortunate to receive an NIH Mentored Patient-Oriented Research Career Development (K23) award to continue this work.

I am also interested in the effects of obesity on hormonal and metabolic parameters.  Using clinical data, I have worked with colleagues in the Pediatric Endocrine Unit to demonstrate that children presenting with short stature who have relatively higher BMI are likely to be over-diagnosed with GH deficiency as assessed by standard GH stimulation tests (see Figure).  In addition, I have worked with others in my research group to examine the interrelationship between subclinical inflammation of obesity and glucose homeostasis.  We recently completed a study of the effects of TNF-alpha antagonism with etanercept on glucose parameters in adults with obesity and features of metabolic syndrome.  In the future, I hope to extend this work to the pediatric population, investigating hormonal and cardiometabolic consequences of obesity as well as potential treatments.












Stanley TL, Joy T, Hadigan CM, Liebau JG, Makimura H, Chen CY, Thomas BJ, Weise SB, Robbins GK, Grinspoon SK.  Effects of Switching from Lopinavir/ritonavir to Atazanavir/ritonavir on Muscle Glucose Uptake and Visceral Fat in HIV Infected Patients.  AIDS. 2009; 23:1349–1357.

Stanley TL, Levitsky LL, Grinspoon SK, Misra MM.  Effects of Body Mass Index on Peak Growth Hormone Response to Provocative Testing in Children with Short Stature.  J Clin Endocrinol Metab.  2009.  94: 4875-4881.

Zanni MV*, Stanley TL*, Makimura H, Chen C, Grinspoon SK.  Effects of TNF-alpha Antagonism on E-selectin in Obese Subjects with Metabolic Dysregulation.  Clin Endocrinol.  2010.  73(1):48-54.

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