Abstract Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased ...somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone-sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH-releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk. Further research is needed regarding the long-term efficacy and safety of this treatment modality.
Reply to Maurice and Lemoine Fourman, Lindsay T; Stanley, Takara L; Grinspoon, Steven K
Clinical infectious diseases,
03/2021, Letnik:
72, Številka:
5
Journal Article
Abstract
Context
Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are ...largely unknown.
Objective
To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure.
Methods
We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls. Weight, length, and body mass index (BMI) were abstracted from health records at 0, 2, 6, and 12 months and standardized using World Health Organization growth charts. Analyses were adjusted for maternal age, ethnicity, parity, insurance, and BMI as well as infant sex, birthdate, and breastfeeding.
Results
Infants with in utero COVID-19 exposure vs controls exhibited differential trajectories of weight and BMI, but not length, z-score over the first year of life (study group × time interaction, P < .0001 for weight and BMI). Infants born to mothers with prenatal COVID-19 had lower BMI z-score at birth (effect size: −0.35, 95% CI −0.66 to −0.03) and greater gain in BMI z-score from birth to 12 months (effect size: 0.53, 95% CI 0.06 to 0.99). Birth weight z-score mediated a significant proportion of the relationship between COVID-19 exposure and postnatal growth (estimate ± SE, 32 ± 14%, P = .02).
Conclusion
Infants with in utero COVID-19 exposure exhibited lower birth weight and accelerated weight gain in the first year of life, which may be harbingers of downstream cardiometabolic pathology. Further studies are needed to delineate cardiometabolic sequelae among this emerging global population.
Adrenoleukodystrophy (ALD) is a peroxisomal disorder associated with neurologic decompensation and adrenal insufficiency. Newborn screening for ALD has recently been implemented in five states with ...plans to expand to all 50 states in the United States. Adrenal insufficiency ultimately develops in most males with ALD, but the earliest age of onset is not well established.
These clinical recommendations are intended to address screening for adrenal insufficiency in boys identified to have ALD by newborn screen.
Seven members of the Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee, with clinical experience treating children with ALD and adrenal insufficiency, and a pediatric endocrinologist and laboratory director were selected to be on the working committee.
The authors comprised the working group and performed systematic reviews of the published literature regarding adrenal insufficiency and ALD. The recommendations were reviewed and approved by the larger Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee and then by the Pediatric Endocrine Society Board of Directors.
There is limited literature evidence regarding monitoring of evolving adrenal insufficiency in male infants and children with ALD. The recommendations suggest initiating assessment of adrenal function at diagnosis with ALD and regular monitoring to identify boys with adrenal insufficiency in a timely manner and prevent life-threatening adrenal crisis. These recommendations are intended to serve as an initial guide, with the understanding that additional experience will inform future guidelines.
Obesity is a chronic disease that disproportionately affects individuals from nonmajority racial/ethnic groups in the United States. Research shows that individuals from minority racial/ethnic ...backgrounds consider it important to have access to providers from diverse backgrounds. Health care providers and scientists from minority racial/ethnic groups are more likely than non-Hispanic whites to treat or conduct research on patients from underrepresented groups.
To characterize the racial/ethnic diversity of nutrition- and obesity-focused professional organizations in the United States.
This study assessed race/ethnicity data from several obesity-focused national organizations including The Obesity Society, the Academy of Nutrition and Dietetics (AND), the American Society for Nutrition, and the American Board of Obesity Medicine (ABOM). Each organization was queried via emailed survey to provide data on racial/ethnic representation among their membership in the past 5 y and among elected presidents from 2010 to 2020.
Two of the 3 professional societies queried did not systematically track race/ethnicity data at the time of query. Limited tracking data available from AND show underrepresentation of black (2.6%), Asian (3.9%), Latinx (3.1%), Native Hawaiian or Pacific Islander: (1.3%), or indigenous (American Indian or Alaskan Native: 0.3%) individuals compared with the US population. Underrepresentation of racial/ethnic minorities was also reported for ABOM diplomates (black: 6.0%, Latinx: 5.0%, Native American: 0.2%). Only AND reported having racial/ethnic diversity (20%) among the organization’s presidents within the previous decade (2010–2020).
Findings suggest that 1) standardized tracking of race and ethnicity data is needed to fully assess diversity, equity, and inclusion, and 2) work is needed to increase the diversity of membership and leadership at the presidential level within obesity- and nutrition-focused professional organizations. A diverse cadre of obesity- and nutrition-focused health care professionals is needed to further improve nutrition-related health outcomes, including obesity, cardiovascular disease, diabetes, and undernutrition, in this country.
IMPORTANCE: Among patients infected with human immunodeficiency virus (HIV), visceral adiposity is associated with metabolic dysregulation and ectopic fat accumulation. Tesamorelin, a growth ...hormone–releasing hormone analog, specifically targets visceral fat reduction but its effects on liver fat are unknown. OBJECTIVE: To investigate the effect of tesamorelin on visceral and liver fat. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized, placebo-controlled trial conducted among 50 antiretroviral-treated HIV-infected men and women with abdominal fat accumulation at Massachusetts General Hospital in Boston. The first patient was enrolled on January 10, 2011; for the final patient, the 6-month study visit was completed on September 6, 2013. INTERVENTIONS: Participants were randomized to receive tesamorelin, 2 mg (n=28), or placebo (n=22), subcutaneously daily for 6 months. MAIN OUTCOMES AND MEASURES: Primary end points were changes in visceral adipose tissue and liver fat. Secondary end points included glucose levels and other metabolic end points. RESULTS: Forty-eight patients received treatment with study drug. Tesamorelin significantly reduced visceral adipose tissue (mean change, –34 cm2 95% CI, –53 to –15 cm2 with tesamorelin vs 8 cm2 95% CI, –14 to 30 cm2 with placebo; treatment effect, –42 cm2 95% CI, –71 to –14 cm2; P = .005) and liver fat (median change in lipid to water percentage, –2.0% interquartile range {IQR}, –6.4% to 0.1% with tesamorelin vs 0.9% IQR, –0.6% to 3.7% with placebo; P = .003) over 6 months, for a net treatment effect of –2.9% in lipid to water percentage. Fasting glucose increased in the tesamorelin group at 2 weeks (mean change, 9 mg/dL 95% CI, 5-13 mg/dL vs 2 mg/dL 95% CI, –3 to 8 mg/dL in the placebo group; treatment effect, 7 mg/dL 95% CI, 1-14 mg/dL; P = .03), but changes at 6 months in fasting glucose (mean change, 4 mg/dL 95% CI, –2 to 10 mg/dL with tesamorelin vs 2 mg/dL 95% CI, –4 to 7 mg/dL with placebo; treatment effect, 2 mg/dL 95% CI, –6 to 10 mg/dL; P = .72 overall across time points) and 2-hour glucose (mean change, –1 mg/dL 95% CI, –18 to 15 mg/dL vs –8 mg/dL 95% CI, –24 to 8 mg/dL, respectively; treatment effect, 7 mg/dL 95% CI, –16 to 29 mg/dL; P = .53 overall across time points) were not significant. CONCLUSIONS AND RELEVANCE: In this preliminary study of HIV-infected patients with abdominal fat accumulation, tesamorelin administered for 6 months was associated with reductions in visceral fat and additionally with modest reductions in liver fat. Further studies are needed to determine the clinical importance and long-term consequences of these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01263717
Background. Obesity and lipohypertrophy are common in treated human immunodeficiency virus (HIV) infection and contribute to morbidity and mortality among HIV-infected adults on antiretroviral ...therapy (ART). Methods. We present a consensus opinion on the diagnosis, clinical consequences, and treatment of excess adiposity in adults with treated HIV infection. Results. Obesity and lipohypertrophy commonly occur among HIV-infected adults on ART and may have overlapping pathophysiologies and/or synergistic metabolic consequences. Traditional, HIV-specific, and ART-specific risk factors all contribute. The metabolic and inflammatory consequences of excess adiposity are critical drivers of non-AIDS events in this population. Although promising treatment strategies exist, further research is needed to better understand the pathophysiology and optimal treatment of obesity and lipohypertrophy in the modern ART era. Conclusions. Both generalized obesity and lipohypertrophy are prevalent among HIV-infected persons on ART. Aggressive diagnosis and management are key to the prevention and treatment of end-organ disease in this population and critical to the present and future health of HIV-infected persons.
Objective: Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase ...inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. Design: We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily versus identical placebo among participants on INSTI-based regimens at baseline. Methods: In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms. Results: Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median interquartile range: -25 -93, -2 vs. 14 3, 41 cm 2 , P = 0.001), hepatic fat (-4.2% -12.3%, -2.7% vs. -0.5% -3.9%, 2.7%, P = 0.01), and trunk-to-appendicular fat ratio (-0.1 -0.3, 0.0 vs. 0.0 -0.1, 0.1, P = 0.03). Tesamorelin was well-tolerated with a similar frequency of adverse events including hyperglycemia between groups. Conclusions: The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.
Abstract
Human immunodeficiency virus (HIV) imparts increased heart failure risk to women. Among women with HIV (WHIV), immune pathways relating to heart failure precursors may intimate targets for ...heart failure prevention strategies. Twenty asymptomatic, antiretroviral-treated WHIV and 14 non-HIV-infected women matched on age and body mass index underwent cardiac magnetic resonance imaging and immune phenotyping. WHIV (vs non-HIV-infected women) exhibited increased myocardial fibrosis (extracellular volume fraction, 0.34 ± 0.06 vs 0.29 ± 0.04; P = .002), reduced diastolic function (diastolic strain rate, 1.10 ± 0.23 s-1 vs 1.39 ± 0.27 s-1; P = .003), and heightened systemic monocyte activation. Among WHIV, soluble CD163 levels correlated with myocardial fibrosis (r = 0.53; P = .02), while circulating inflammatory CD14+CD16+ monocyte CCR2 expression related directly to myocardial fibrosis (r = 0.48; P = .04) and inversely to diastolic function (r = –0.49; P = .03).
Clinical Trials Registration. NCT02874703.
Antiretroviral-treated women with HIV (WHIV) exhibit increased myocardial fibrosis and decreased diastolic function compared with non-HIV-infected women. Among WHIV, the degree of CCR2 expression on circulating inflammatory CD14+CD16+ monocytes relates directly to myocardial fibrosis and inversely to diastolic function.
Objective
Obesity is a chronic disease that disproportionately affects individuals from nonmajority racial/ethnic groups in the United States. Research shows that individuals from minority ...racial/ethnic backgrounds consider it important to have access to providers from diverse backgrounds. Health care providers and scientists from minority racial/ethnic groups are more likely than their non‐Hispanic White counterparts to treat or conduct research on patients from underrepresented groups. The objective of this study was to characterize the racial/ethnic diversity of nutrition‐ and obesity‐focused professional organizations in the United States.
Methods
This study assessed race/ethnicity data from several obesity‐focused national organizations including The Obesity Society, the Academy of Nutrition and Dietetics (AND), the American Society for Nutrition, and the American Board of Obesity Medicine (ABOM). Each organization was queried via emailed survey to provide data on racial/ethnic representation among their membership in the past 5 years and among elected presidents from 2010 to 2020.
Results
Two of the three professional societies queried did not systematically track race/ethnicity data at the time of query. Limited tracking data available from AND show underrepresentation of Black (2.6%), Asian (3.9%), Latinx (3.1%), Native Hawaiian or Pacific Islander (1.3%), or indigenous (American Indian or Alaskan Native: 0.3%) individuals compared with the US population. Underrepresentation of racial/ethnic minorities was also reported for ABOM diplomates (Black: 6.0%, Latinx: 5.0%, Native American: 0.2%). Only AND reported having racial/ethnic diversity (20%) among the organization’s presidents within the previous decade (2010–2020).
Conclusions
Findings suggest that (1) standardized tracking of race and ethnicity data is needed to fully assess diversity, equity, and inclusion, and (2) work is needed to increase the diversity of membership and leadership at the presidential level within obesity‐ and nutrition‐focused professional organizations. A diverse cadre of obesity‐ and nutrition‐focused health care professionals is needed to further improve nutrition‐related health outcomes, including obesity, cardiovascular disease, diabetes, and undernutrition, in this country.
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