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Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU* [m.sup.-2] * [min.sup.-1]) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[[sup.18F]]fluoro-D-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 [+ or -] 0.4 vs. 2.3 [+ or -] 0.5 [micro]mol * kg [tissue.sup.-1] * [min.sup.-1], P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal ([r.sup.2] = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area (r = -0.75, P = 0.008), and whole body glucose disposal (r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process. positron emission tomography; adipose tissue; insulin resistance; human immunodeficiency virus-lipodystrophy

Background: Substantial loss of muscle mass occurs among men with AIDS wasting.Objective: To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting.Design: Randomized, controlled trial.Setting: University hospital.Patients: 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%).Intervention: In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks.Measurements: Cross-sectional muscle area and other indices of muscle mass.Results: Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052).Conclusions: In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting. [ABSTRACT FROM AUTHOR]

Context: Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor.Objective: To investigate the effects of low-dose physiological GH administration on body composition, glucose, and cardiovascular parameters in patients with human immunodeficiency virus (HIV) having abdominal fat accumulation and relative GH deficiency.Design, Setting, and Patients: A randomized, double-blind, placebo-controlled trial of 56 patients with HIV, abdominal fat accumulation, and reduced GH secretion (peak GH <7.5 ng/mL) conducted at a US academic medical center between November 2003 and October 2007.Intervention: Patients were randomly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 (IGF-1) range for 18 months. Starting dose was 2 microg/kg/d and increased to maximum dose of 6 microg/kg/d (average dose, 0.33 mg/d).Main Outcome Measures: Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry. Secondary outcomes included glucose, IGF-1, blood pressure (BP), and lipids. Treatment effect was the difference in the change between GH and placebo groups, using all available data.Results: Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses. Visceral adipose tissue area (treatment effect [last-value-carried-forward analysis {n = 56}, -19 cm(2); 95% confidence interval {CI}, -37 to -0.3 cm(2)], -19 cm(2); 95% CI, -38 to -0.5 cm(2); P = .049); trunk fat (-0.8 kg; 95% CI, -1.5 to -0.04 kg; P = .04); diastolic BP (-7 mm Hg; 95% CI, -11 to -2 mm Hg; P = .006); and triglycerides (-7 mg/dL, P = .002) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group (treatment effect, 22 mg/dL; 95% CI, 6-37 mg/dL; P = .009). The IGF-1 levels increased (treatment effect, 129 ng/mL; 95% CI, 95-164 ng/mL; P < .001). Adverse events were not increased for GH vs placebo (23%; 95% CI, 9%-44% vs 28%; 95% CI, 13%-47%; P = .70).Conclusions: In HIV-associated abdominal fat accumulation and relative GH deficiency, low-dose GH received for 18 months resulted in significantly reduced visceral fat and truncal obesity, triglycerides, and diastolic BP, but 2-hour glucose levels on glucose tolerance testing were increased.Trial Registration: clinicaltrials.gov Identifier: NCT00100698. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antiretroviral therapy (ART)-associated lipoatrophy involves mitochondrial dysfunction. Iron metabolism impacts mitochondrial function and oxidative stress. Mitochondrial haplogroups and hemochromatosis gene (HFE) polymorphisms have been associated with ART-induced neuropathy. We assessed relationships between these variants and lipoatrophy. METHODS: The AIDS Clinical Trials Group 384 study randomized ART-naive individuals to receive didanosine-stavudine or zidovudine-lamivudine, combined with efavirenz and/or nelfinavir. Substudy A5005s evaluated fat distribution by dual-energy X-ray absorptiometry (DEXA). We characterized HFE polymorphisms 845G>A and 187C>G and European mitochondrial haplogroups in A5005s participants who consented to genetic analyses. RESULTS: Among 96 participants (58% were white, and 10% were female) with baseline and 48 or 64 week DEXA data, the median limb fat change was -8.8% (interquartile range, -28.7% to +15.6%). HFE 187C/G heterozygotes (n = 23) had less limb fat loss than 187C/C homozygotes (n = 71) (+6.1% vs. -12.5%; P = .02) and were less likely to develop lipoatrophy after adjustment for age, sex, race, and ART randomization (odds ratio, 0.31; 95% confidence interval, 0.10-0.95; P = .04). Among non-Hispanic white participants, median limb fat change was +26.1% among 5 participants with mitochondrial haplogroup J, compared with -9.7% among 49 participants with other mitochondrial haplogroups (P = .07). CONCLUSIONS: HFE 187C>G and, possibly, mitochondrial haplogroup J gave relative protection against lipoatrophy during ART in A5005s. These associations should be replicated in other studies. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Objectives Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. Methods Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. Results Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. Conclusions We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Context: Reduced growth hormone (GH) concentrations are observed in men with human immunodeficiency virus (HIV) lipodystrophy.Objective: To investigate the effects of growth hormone-releasing hormone (GHRH), a GH secretagogue, in treatment of HIV lipodystrophy.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted at a research center in the United States between October 2002 and June 2003 and enrolling 31 HIV-infected men aged 18 to 60 years with evidence of lipodystrophy.Interventions: Participants were assigned to receive GHRH (1 mg subcutaneously twice daily) or placebo for 12 weeks.Main Outcome Measures: The primary outcome was change in concentrations of insulin-like growth factor 1 (IGF-1) to detect overall change in GH levels in response to GHRH. Secondary end points included body composition by dual-energy x-ray absorptiometry and computed tomography, lipodystrophy ratings, and levels of glucose, insulin, and lipids.Results: Mean (SD) IGF-1 concentrations increased significantly in the GHRH group vs the placebo group (104 [110] ng/mL vs 6 [44] ng/mL, P =.004). Lean body mass significantly increased in the GHRH group vs the placebo group (0.9 [1.3] kg vs -0.3 [1.7] kg, P =.04), trunk fat significantly decreased (-0.4 [0.7] kg vs 0.2 [0.6] kg, P =.03), and the ratio of trunk to lower extremity fat improved significantly (-0.22 [0.32] vs 0.14 [0.29], P =.005). Abdominal visceral fat was reduced (-19.2 [36.6] cm2 vs 2.3 [24.3] cm2, P =.07) and the ratio of abdominal visceral fat to abdominal subcutaneous fat improved significantly more in the GHRH group (-0.19 [0.28] vs 0.07 [0.27], P =.02). Both physician and patient rating of lipodystrophy in the arms, legs, and abdomen also improved significantly. Levels of glucose, insulin, and lipids did not change significantly.Conclusions: GHRH was well tolerated and effectively increased levels of IGF-1 in HIV-infected men with lipodystrophy. Total and regional body composition improved in response to GHRH, with increased lean mass and reduced truncal and visceral fat. Use of GHRH may potentially be a beneficial treatment strategy for this population. [ABSTRACT FROM AUTHOR]

Background: Patients with HIV infection who are treated with antiretroviral agents often lose subcutaneous fat and have metabolic abnormalities, including insulin resistance and reduced adiponectin levels, which may be related to disrupted subcutaneous adipogenesis and altered peroxisome proliferator-activated receptor-gamma signaling.Objective: To investigate the effects of rosiglitazone (4 mg/d), a peroxisome proliferator-activated receptor-gamma agonist, in HIV-infected men and women with hyperinsulinemia and lipoatrophy.Design: A randomized, double-blind, placebo-controlled, 3-month study.Setting: University hospital.Patients: 28 HIV-infected men and women with hyperinsulinemia and lipoatrophy.Measurements: Insulin sensitivity measured by euglycemic hyperinsulinemic clamp testing; subcutaneous leg fat area measured by computed tomography; adiponectin, free fatty acid, and lipid levels; and safety variables.Results: Rosiglitazone, when compared with placebo, improved insulin sensitivity (mean [+/-SD] change, 1.5 +/- 2.1 mg of glucose/kg of lean body mass per minute vs. -0.4 +/- 1.6 mg/kg per minute; P = 0.02), increased adiponectin levels (mean [+/-SD], 2.2 +/- 2.2 micro g/mL vs. 0.1 +/- 1.1 microg/mL; P = 0.006), and reduced free fatty acid levels (mean [+/-SD], -0.09 +/- 0.1 mmol/L vs. 0.01 +/- 0.1 mmol/L; P = 0.02). Mean percentage (+/-SD) of body fat (1.38% +/- 3.03% vs. -0.83% +/- 2.76%; P = 0.03) and subcutaneous leg fat area (2.3 +/- 8.4 cm2 vs. -0.9 +/- 1.9 cm2; P = 0.02) increased significantly with rosiglitazone compared with placebo. Mean total cholesterol levels (+/-SD) also increased with rosiglitazone compared with placebo (0.6 +/- 1.0 mmol/L [25 +/- 37 mg/dL] vs. -0.4 +/- 0.6 mmol/L [-15 +/- 25 mg/dL]; P = 0.007).Limitations: The study was relatively small and of short duration.Conclusions: The authors demonstrated positive effects of rosiglitazone on lipoatrophy; insulin sensitivity; and metabolic indices, including adiponectin levels, in HIV-infected patients with lipoatrophy and insulin resistance. Peroxisome proliferator-activated receptor-gamma agonists may correct the metabolic abnormalities associated with disrupted adipogenesis in this population. Further studies must determine the clinical utility of such agents in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background: Anorexia nervosa is highly prevalent among young women.Objective: To determine prevalence and predictive factors for regional bone loss.Design: Prospective cohort analysis.Setting: University hospital.Patients: 130 women with anorexia nervosa.Measurements: Dual-energy x-ray absorptiometry.Results: The prevalence of osteopenia (-1.0 SD >/= T-score > -2.5 SD) and osteoporosis (T-score Conclusions: Bone mineral density is reduced at several skeletal sites in most women with anorexia nervosa. Weight, but not estrogen use, is a significant predictor of BMD in this population at all skeletal sites. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lean body mass is an important predictor of survival and functional status in patients with AIDS wasting. The bias between different techniques for assessing body composition in AIDS wasting is not known. DESIGN: We compared total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold-thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting (weight < 90% of ideal body weight, or weight loss > 10% of original, or both). None of the subjects exhibited clinical lipodystrophy. Comparisons were made by using different BIA equations. RESULTS: Lean body mass determined by DXA was highly correlated with TBK in men (r = 0.79, P: < 0.0001) and women (r = 0.84, P: < 0.0001). FFM(BIA) and FFM(DXA) were significantly different (P: < 0.01 in men and P: < 0.0001 in women). The difference between FFM(DXA) and FFM(BIA) was significantly greater with greater weight and body fat, particularly in HIV-infected women (r = -0.39, P: = 0.001 for weight; r = -0.60, P: < 0.0001 for fat). The comparability of FFM and fat mass determined by DXA and BIA was dependent on the specific BIA equation used. Among men, no single BIA equation was more highly predictive of fat mass and FFM in comparison with DXA. CONCLUSIONS: The differences between DXA, BIA, and SKF in the determination of fat mass and FFM are significant in patients with AIDS wasting. BIA overestimates FFM compared with DXA in those with greater body fat. Standard BIA equations may not accurately estimate FFM and fat mass in men and women with AIDS wasting. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Context: A syndrome of lipodystrophy, characterized by fat redistribution and insulin resistance, has been estimated to affect the majority of human immunodeficiency virus (HIV)-infected individuals who are treated with combination antiretroviral therapy. There are no proven therapies for the metabolic disturbances associated with HIV lipodystrophy syndrome.Objective: To determine the safety and efficacy of metformin therapy in HIV-infected patients with fat redistribution and abnormal glucose homeostasis.Design and Setting: Randomized, double-blind, placebo-controlled pilot study conducted in a university hospital between December 1998 and January 2000.Patients: Twenty-six HIV-infected, nondiabetic patients with fat redistribution and abnormal oral glucose tolerance test (OGTT) results, hyperinsulinemia, or both.Interventions: Patients were randomly assigned to receive metformin, 500 mg twice daily (n = 14), or identical placebo (n = 12), for 3 months.Main Outcome Measures: Insulin area under the curve (AUC), calculated 120 minutes following a 75-g OGTT at baseline vs at 3-month follow-up and compared between treatment groups.Results: Patients treated with metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT (-2930 [912] vs -414 [432] microIU/mL [-20349 6334 vs -2875 3000 pmol/L]; P =.01), weight (-1.3 [0.6] vs 1.1 [0.4] kg; P =.005), and diastolic blood pressure (-5 [4] vs 5 [2] mm Hg; P =.009) vs controls, respectively. Metformin therapy was associated with a decrease in visceral abdominal fat (VAT; -1115 [819] vs 1191 [699] mm(2); P =.08) and a proportional reduction in subcutaneous abdominal fat (SAT); the VAT-SAT ratio was unchanged in metformin-treated vs placebo-treated patients. No increase in lactate or liver transaminase levels was observed with metformin treatment. Mild diarrhea was the most common adverse effect of metformin. No patient discontinued therapy because of adverse effects.Conclusions: This study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy. JAMA. 2000;284:472-477 [ABSTRACT FROM AUTHOR]

Background: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported.Objective: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques.Design: Retrospective case series.Setting: Tertiary care center.Patients: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996.Intervention: Transsphenoidal adenomectomy and as-needed adjunctive therapy.Measurement: Record review with follow-up interview.Results: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2).Conclusion: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder. [ABSTRACT FROM AUTHOR]

Background: Development of successful anabolic strategies to reverse the loss of lean body mass is of critical importance to increase survival in men with the AIDS wasting syndrome. Hypogonadism, an acquired endocrine deficiency state characterized by loss of testosterone, occurs in more than half of all men with advanced HIV disease. It is unknown whether testosterone deficiency contributes to the profound catabolic state and loss of lean body mass associated with the AIDS wasting syndrome.Objective: To investigate the effects of physiologic testosterone administration on body composition, exercise functional capacity, and quality of life in androgen-deficient men with the AIDS wasting syndrome.Design: Randomized, double-blind, placebo-controlled study.Setting: University medical center.Patients: 51 HIV-positive men (age 42 +/- 8 years) with wasting (body weight < 90% of ideal body weight or weight loss > 10% of baseline weight) and a free testosterone level less than 42 pmol/L (normal range for men 18 to 49 years of age, 42 to 121 pmol/L [12.0 to 35.0 pg/mL]).Intervention: Patients were randomly assigned to receive testosterone enanthate, 300 mg, or placebo intramuscularly every 3 weeks for 6 months.Measurements: Change in fat-free mass was the primary end point. Secondary clinical end points were weight, lean body mass, muscle mass, exercise functional capacity, and change in perceived quality of life. Virologic variables were assessed by CD4 count and viral load.Results: Compared with patients who received placebo, testosterone-treated patients gained fat-free mass (-0.6 kg and 2.0 kg; P = 0.036), lean body mass (0.0 kg and 1.9 kg; P = 0.041), and muscle mass (-0.8 kg and 2.4 kg; P = 0.005). The changes in weight, fat mass, total-body water content, and exercise functional capacity did not significantly differ between the groups. Patients who received testosterone reported benefit from the treatment (P = 0.036), feeling better (P = 0.033), improved quality of life (P = 0.040), and improved appearance (P = 0.021). Testosterone was well tolerated in all patients.Conclusions: Physiologic testosterone administration increases lean body mass and improves quality of life among androgen-deficient men with the AIDS wasting syndrome. [ABSTRACT FROM AUTHOR]

Reports global developments related to AIDS disease as of March 2000. Incidence of hyperinsulinemia in HIV; Effects of hypogonadism and testosterone administration of depression indices on HIV; Assessment of zinc protoporphyrin levels in advanced AIDS.

Research shows that a diverse faculty improves academic, clinical, and research outcomes in higher education. Despite that, persons in minority groups, usually categorized by race or ethnicity, are underrepresented in academia (URiA). The Nutrition Obesity Research Centers (NORCs), supported by the National Institute of Diabetes and Digestive and Kidney Diseases, hosted workshops on five separate days in September and October 2020. NORCs convened these workshops to identify barriers and facilitators for diversity, equity, and inclusion (DEI) and provide specific recommendations to improve DEI within obesity and nutrition for individuals from URiA groups. Recognized experts on DEI presented each day, after which the NORCs conducted breakout sessions with key stakeholders who engage in nutrition and obesity research. The breakout session groups included early-career investigators, professional societies, and academic leadership. The consensus from the breakout sessions was that glaring inequities affect URiA in nutrition and obesity, particularly related to recruitment, retention, and advancement. Recommendations from the breakout sessions to improve DEI across academia focused on six themes: (1) recruitment, (2) retention, (3) advancement, (4) intersectionality of multiple challenges (e.g., being Black and a woman), (5) funding agencies, and (6) implementation of strategies to address problems related to DEI., (© 2023 The Obesity Society and The American Society for Nutrition.)

Research shows that a diverse faculty improves academic, clinical, and research outcomes in higher education. Despite that, persons in minority groups, usually categorized by race or ethnicity, are underrepresented in academia (URiA). The Nutrition Obesity Research Centers (NORCs), supported by the NIDDK, hosted workshops on five separate days in September and October 2020. NORCs convened these workshops to identify barriers and facilitators for diversity, equity, and inclusion (DEI) and provide specific recommendations to improve DEI within obesity and nutrition for individuals from URiA groups. Recognized experts on DEI presented each day, after which the NORCs conducted breakout sessions with key stakeholders who engage in nutrition and obesity research. The breakout session groups included early-career investigators, professional societies, and academic leadership. The consensus from the breakout sessions was that glaring inequities affect URiA in nutrition and obesity, particularly related to recruitment, retention, and advancement. Recommendations from the breakout sessions to improve DEI across the academe focused on six themes: (1) recruitment, (2) retention, (3) advancement, (4) intersectionality of multiple challenges (e.g., being Black and a woman), (5) funding agencies, and (6) implementation of strategies to address problems related to DEI., (Copyright © 2023 The Obesity Society, The American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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., (© 2021 The Obesity Society and The American Society for Nutrition.)

People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n = 600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n = 8111) from blood DNA-derived exome sequences. We observed that HIV is associated with a twofold increase in CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p = 0.005). We also observed that ASXL1 is the most commonly mutated CHIP-associated gene in PLWH. Our results suggest that CHIP may contribute to the excess cardiovascular risk observed in PLWH., (© 2022. The Author(s).)

Food systems are at the center of a brewing storm consisting of a rapidly changing climate, rising hunger and malnutrition, and significant social inequities. At the same time, there are vast opportunities to ensure that food systems produce healthy and safe food in equitable ways that promote environmental sustainability, especially if the world can come together at the UN Food Systems Summit in late 2021 and make strong and binding commitments toward food system transformation. The NIH-funded Nutrition Obesity Research Center at Harvard and the Harvard Medical School Division of Nutrition held their 22nd annual Harvard Nutrition Obesity Symposium entitled "Global Food Systems and Sustainable Nutrition in the 21st Century" in June 2021. This article presents a synthesis of this symposium and highlights the importance of food systems to addressing the burden of malnutrition and noncommunicable diseases, climate change, and the related economic and social inequities. Transformation of food systems is possible, and the nutrition and health communities have a significant role to play in this transformative process., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: In addition to traditional cardiovascular (CV) risk factors, antiretroviral therapy, lifestyle, and human immunodeficiency virus (HIV)-related factors may contribute to future CV events in persons with HIV (PWH)., Methods: Among participants in the global REPRIEVE randomized trial, we characterized demographics and HIV characteristics relative to ACC/AHA pooled cohort equations (PCE) for atherosclerotic CV disease predicted risk and CV health evaluated by Life's Simple 7 (LS7; includes smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and glucose)., Results: Among 7382 REPRIEVE participants (31% women, 45% Black), the median PCE risk score was 4.5% (lower and upper quartiles Q1, Q3: 2.2, 7.2); 29% had a PCE score <2.5%, and 9% scored above 10%. PCE score was related closely to known CV risk factors and modestly (<1% difference in risk score) to immune function and HIV parameters. The median LS7 score was 9 (Q1, Q3: 7, 10) of a possible 14. Only 24 participants (0.3%) had 7/7 ideal components, and 36% had ≤2 ideal components; 90% had <5 ideal components. The distribution of LS7 did not vary by age or natal sex, although ideal health was more common in low sociodemographic index countries and among Asians. Poor dietary and physical activity patterns on LS7 were seen across all PCE scores, including the lowest risk categories., Conclusions: Poor CV health by LS7 was common among REPRIEVE participants, regardless of PCE. This suggests a critical and independent role for lifestyle interventions in conjunction with conventional treatment to improve CV outcomes in PWH. Clinical Trials Registration: NCT02344290. AIDS Clinical Trials Group study number: A5332., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: 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., Objectives: 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 y and among elected presidents from 2010 to 2020., Results: 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)., 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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density., Design: Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated., Methods: CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader., Results: Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, P = 0.80) and SAT density (-94 HU tesamorelin, -95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P < 0.0001; SAT: +4.0 (8.7) HU tesamorelin, +0.3 (4.8) HU placebo, P < 0.0001]. The tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT [+2.3 HU, 95% confidence interval (4.5-7.3), P = 0.001) or SAT (+3.5 HU, 95% confidence interval (2.3-4.7), P < 0.001] area change., Conclusion: In PWH with central adiposity who experienced VAT quantity reductions on tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that tesamorelin also improves VAT and SAT quality in this group., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Metabolic complications relating to complex effects of viral and immune-mediated mechanisms are now a focus of clinical care among persons living with human immunodeficiency virus (PLHIV), and obesity is emerging as a critical problem. To address knowledge gaps, the US National Institutes of Health sponsored a symposium in May 2018 entitled "Obesity and Fat Metabolism in HIV-infected Individuals." Mechanisms relating to adipose dysfunction and fibrosis, immune function, inflammation, and gastrointestinal integrity were highlighted as contributors to obesity among PLHIV. Fibrotic subcutaneous adipose tissue is metabolically dysfunctional and loses its capacity to expand, leading to fat redistribution, including visceral obesity and ectopic fat accumulation, promoting insulin resistance. Viral proteins, including viral protein R and negative regulatory factor, have effects on adipogenic pathways and cellular metabolism in resident macrophages and T cells. HIV also affects immune cell trafficking into the adipose compartments, with effects on adipogenesis, lipolysis, and ectopic fat accumulation. Key cellular metabolic functions are likely to be affected in PLHIV by gut-derived cytokines and altered microbiota. There are limited strategies to reduce obesity specifically in PLHIV. Enhancing our understanding of critical pathogenic mechanisms will enable the development of novel therapeutics that may normalize adipose tissue function and distribution, reduce inflammation, and improve insulin sensitivity in PLHIV., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Objective: HIV-infected women are burdened by depression and anxiety, which may impact adherence to antiretroviral therapy and overall quality of life. Yet, little is known about the scope of psychological symptoms in the growing number of HIV-infected women reaching menopause, when affective symptoms are more prevalent in the general population. We conducted a longitudinal study to compare affective symptoms between perimenopausal HIV-infected and non-HIV-infected women., Methods: The Center for Epidemiologic Studies Depression Scale (CES-D), and the Generalized Anxiety Disorder scale (GAD-7) were completed at baseline and 12 months among 33 HIV-infected and 33 non-HIV-infected perimenopausal women matched by race, age, menstrual patterns, and BMI. Linear regression models estimated the relationship of baseline GAD-7 and CES-D scores with clinical factors., Results: All women were perimenopausal at baseline, and the vast majority remained perimenopausal throughout follow-up. HIV status was associated with higher baseline CES-D scores (median [interquartile range] 21 [12, 29] vs 10 [5, 14]; P = 0.03) and GAD-7 scores (7 [5, 15] vs 2 [1, 7]; P = 0.01), controlling for smoking, substance use, and antidepressant use. Depressive symptoms and anxiety remained significantly higher in the HIV-infected women at 12 months (P ≤ 0.01). Significant relationships of depressive symptoms (P = 0.048) and anxiety (P = 0.02) with hot flash severity were also observed., Conclusions: Perimenopausal HIV-infected women experienced a disproportionately high level of affective symptom burden over a 12-month observation period. Given the potential for these factors to influence adherence to HIV clinical care and quality of life, careful assessment and referral for treatment of these symptoms is essential.

Cardiovascular disease (CVD) rates are 50% to 100% higher in human immunodeficiency virus (HIV) patients. Traditional risks account for only 25% of this excess risk. Excess CVD risk in HIV may relate in part to increases in ectopic adipose depots. CVD in HIV-infection is characterized by atypical highly vulnerable plaque lesions, which are inflamed, in tight relationship to immune, and monocyte activation pathways. Using 18 fluorine-2-deoxy-D-glucose positron-emission tomography imaging techniques, we have shown increased arterial inflammation which persists even after effective antiretroviral therapy. More recent studies, using a novel macrophage specific imaging agent in humans, have shown highly increased inflammatory patterns in large vessels in HIV. In addition, statins may be uniquely valuable among HIV patients, not only lowering low-density lipoprotein, but also reducing monocyte chemo-attraction, and immune activation pathways. These data have led the National Institutes of Health to fund the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), the first large multicenter primary CVD prevention trial in HIV, aimed at assessing inflammatory mechanisms of CVD in HIV., Competing Interests: Potential Conflicts of Interest: Dr. Grinspoon has received consulting fees from Theratechnologies, Gilead, Merck, BMS, NovoNordisk, AstaZeneca, and Navidea; and research funds from Gilead, BMS, Navidea, Theratechnologies, Immunex, and KOWA; and royalties from -UpToDate, unrelated to this manuscript. This work was supported by DK040561 and the Nutrition Obesity Research Center at Harvard.

Inflammation is a critical factor in early atherosclerosis and its progression to myocardial infarction. The search for valid surrogate markers of arterial vascular inflammation led to the increasing use of positron emission tomography/computed tomography. Indeed, vascular inflammation is associated with future risk for myocardial infarction and can be modulated with short-term therapies, such as statins, that mitigate cardiovascular risk. However, to better understand vascular inflammation and its mechanisms, a panel was recently convened of world experts in immunology, human translational research, and positron emission tomographic vascular imaging. This contemporary review first strives to understand the diverse roles of immune cells implicated in atherogenesis. Next, the authors describe human chronic inflammatory disease models that can help elucidate the pathophysiology of vascular inflammation. Finally, the authors review positron emission tomography-based imaging techniques to characterize the vessel wall in vivo., (Published by Elsevier Inc.)

Background: Women's under-representation in HIV and cardiovascular disease (CVD) research suggests a need for novel strategies to ensure robust representation of women in HIV-associated CVD research., Objective: To elicit perspectives on CVD research participation among a community-sample of women with or at risk for HIV, and to apply acquired insights toward the development of an evidence-based campaign empowering older women with HIV to participate in a large-scale CVD prevention trial., Methods: In a community-based setting, we surveyed 40 women with or at risk for HIV about factors which might facilitate or impede engagement in CVD research. We applied insights derived from these surveys into the development of the Follow YOUR Heart campaign, educating women about HIV-associated CVD and empowering them to learn more about a multi-site HIV-associated CVD prevention trial: REPRIEVE., Results: Endorsed best methods for learning about a CVD research study included peer-to-peer communication (54%), provider communication (46%) and video-based communication (39%). Top endorsed non-monetary reasons for participating in research related to gaining information (63%) and helping others (47%). Top endorsed reasons for not participating related to lack of knowledge about studies (29%) and lack of request to participate (29%). Based on survey results, the REPRIEVE Follow YOUR Heart campaign was developed. Interwoven campaign components (print materials, video, web presence) offer provider-based information/knowledge, peer-to-peer communication, and empowerment to learn more. Campaign components reflect women's self-identified motivations for research participation - education and altruism., Conclusions: Investigation of factors influencing women's participation in HIV-associated CVD research may be usefully applied to develop evidence-based strategies for enhancing women's enrollment in disease-specific large-scale trials. If proven efficacious, such strategies may enhance conduct of large-scale research studies across disciplines.

Objective: To investigate differences in subclinical coronary atherosclerotic plaque and markers of immune activation among HIV-infected and non-HIV-infected women categorized by degree of ovarian reserve and menopause status., Design: Cross-sectional evaluation., Methods: Seventy-four women (49 HIV-infected, 25 non-HIV-infected) without known cardiovascular disease (CVD) were classified as premenopausal, premenopausal with reduced ovarian reserve, or postmenopausal based on menstrual history and anti-Müllerian hormone (AMH) levels. Participants underwent contrast-enhanced coronary computed tomography angiography and immune phenotyping. Comparisons in coronary atherosclerotic plaque burden and immune markers were made between the HIV-infected and non-HIV-infected women overall and within the HIV-infected and non-HIV-infected women by reproductive classification group., Results: Among the overall group of HIV-infected women, the women with reduced ovarian reserve (undetectable AMH) had a higher prevalence of coronary atherosclerotic plaque (52 versus 6%, P = 0.0007) and noncalcified plaque (48 versus 6%, P = 0.002), as well as higher levels of log sCD163 (P = 0.0004) and log MCP-1 (P = 0.006), compared with the premenopausal women with measurable AMH. Furthermore, reduced ovarian reserve in the HIV-infected group related to noncalcified plaque, controlling for traditional CVD risk factors (P = 0.04) and sCD163 (P = 0.03)., Conclusion: HIV-infected women with reduced ovarian reserve have increased subclinical coronary atherosclerotic plaque compared with premenopausal women in whom AMH is measurable. This relationship holds when controlling for CVD risk factors (including age) and immune activation. Our findings demonstrate that reduced ovarian reserve may contribute to CVD burden in HIV-infected women and support a comprehensive assessment of CVD risk prior to completion of menopause in this population.

Since the publication of the first issue of this journal in November 2005, our understanding of the endocrine system has evolved, with the identification of novel hormones and novel endocrine roles for previously identified molecules. Here, we have asked six of our Advisory Board Members to comment on how these insights have led to the recognition that many organs and tissues that were not widely considered part of the classic endocrine system in the past have important endocrine functions.

Background: Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study., Methods: We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors., Results: Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque., Conclusions: sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)