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Overview of Cohort. Of the 24 HIV-infected patients with lipodystrophy, 10 had lipoatrophy (Atrophy), 4 had lipohypertrophy (Hyper), and 10 had Mixed type lipodystrophy (Mix). Patients with Hyper and Mix type lipodystrophy were grouped (Hyper/Mix). One control was excluded from data analyses due to recent hip surgery. Two patients with Atrophy, 1 Mix, and five patients without lipodystrophy (Non-Lipo) did not have DXA made, and were therefore not included in analyses of DXA scans. Two patients in the Non-Lipo did not have CT made, and were therefore not included in analyses of CT scans. Abbreviations: CT: Computed tomography; DXA: Dual energy X-ray absorptiometry
Source publication
HIV-infected patients could exhibit accelerated ageing, since age-associated complications like sarcopenia; increased inflammation; lipodystrophy with loss of subcutaneous adipose tissue and/or gain of visceral adipose tissue (VAT); and cardiovascular disease occur at an earlier age. Inflammation is involved in age-associated complications. However...
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Citations
... In recent years, there has been a growing interest in studying the relationship between sarcopenia, immunity, and inflammation. As individuals age, they often experience a chronic low-grade pro-inflammatory state characterized by and increase in pro-inflammatory cytokines and a decrease in immune cell function (Wilson, necrosis factor-α (TNF-α) compared to healthy young men and women, and interleukin-6 (IL-6) is significantly associated with sarcopenia (Greiwe, Cheng, Rubin, Yarasheski, & Semenkovich, 2001;Langkilde et al., 2015). The elevated expression of these cytokines can contribute to muscle atrophy (Crossland, Constantin-Teodosiu, Gardiner, Constantin, & Greenhaff, 2008;Yakabe et al., 2018). ...
Sarcopenia is a condition characterized by the age-related loss of skeletal muscle mass and function. The pathogenesis of the disease is influenced by chronic low-grade inflammation. However, the specific changes in the immune landscape changes of sarcopenic muscle are not yet fully understood. To gain insights into the immune cell composition and interactions, we combined single-nuclei RNA sequencing data, bulk RNA sequencing datasets, and comprehensive bioinformatic analyses on skeletal muscle samples from young, aged, and sarcopenic individuals. Histological staining was then performed on skeletal muscles to validate the distribution of immune cells in clinical samples. Overall, we analyzed the transcriptomes of 101,862 single nuclei, revealing a total of 10 major cell types and 6 subclusters of immune cell types within the human skeletal muscle tissues. Among the immune cells, macrophages constituted the largest immune fraction. A specific marker gene LYVE1 for skeletal muscle macrophages was further identified. Cellular subclasses included four distinct groups of resident macrophages, which play a different role in physiological or non-physiological conditions. Using bulk RNA sequencing data, we identified strong enrichment for a macrophage-rich inflammation in sarcopenia. Our findings demonstrate age-related changes in the composition and cross-talk of immune cells, which contribute to chronic inflammation. Furthermore, macrophages emerge as a potential therapeutic target, thus advancing our understanding of the pathogenesis of sarcopenia.
... 14 In PWH, inflammatory markers remain elevated compared with controls without HIV, even with effective antiretroviral therapy (ART), and have an important role in the course of HIV infection. 15 Aging-associated sex hormone changes also increase body fat accumulation and strongly predict muscle strength and physical function loss. However, the interplay among adiposity, inflammation, and physical function is understudied in PWH. ...
... 33 In our study, increased abdominal adiposity was associated with higher levels of hsCRP, which appears central in both adiposity-and sarcopenia-associated inflammation. 15 Although hsCRP was not augmented in participants with low handgrip or low SPPB among our participants, Erlandson et al 34 have previously demonstrated that frailty was associated with 69% higher hsCRP concentrations (P , 0.01) among men with HIV (n = 296), independent of comorbid conditions. ...
Background
This study examined the relationships among adiposity, handgrip, physical function, inflammation (i.e., senescence-associated secretory phenotype [SASP] chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV (PWH).
Methods
This cross-sectional exploratory study included 150 PWH aged ≥40 years (67.3% of participants were males). Our measures included: 1) body mass index (BMI) and waist circumference as measures of adiposity; 2) handgrip as a measure of muscle strength; 3) Short Physical Performance Battery as a measure of physical function; 4) interleukin-6, tumor necrosis factor alpha receptor II (TNFRII), high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 10 (CXCL10), and C-X3-C motif chemokine ligand 1 aka fractalkine as SASP chemokines; and 5) free testosterone, estradiol, sex hormone binding globulin, and dehydroepiandrosterone (DHEA) as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function.
Results
74% ( n =111) of participants were classified as overweight or obese and 53.3% ( n =80) presented with abdominal obesity. After controlling for age and sex, BMI was positively associated with estradiol (β=0.043, p <0.01), and waist circumference was positively associated with hsCRP (β=2.151, p <0.01). After controlling for sex, age was positively associated with CXCL10 (β=0.024, p =0.03) and TNFRII (β=2.205, p =0.01). After controlling for age and sex, SPPB was negatively associated with DHEA (β=-0.004, p =0.01); no statistically significant associations were observed for handgrip.
Conclusion
Adiposity levels and aging were associated with inflammation ( i.e. , CXCL10, TNFRII, and hsCRP) among PWH aged 40 years and older.
... One of the physiological reasons for the functional deterioration of the skeletal muscle system in the sarcopenic TBF obesity phenotype is the pro-inflammatory action of excess body fat. The presence of a large amount of fat (i.e., total body, trunk, or visceral) promotes greater production of inflammatory cytokines of the immune system (interleukin-6, tumor necrosis factor-alpha, c-reactive protein) (24)(25)(26) that act as muscle growth inhibitors promoting the loss of muscle mass and function (27). The TBF obesity phenotype did not show a significant association with frailty; on the contrary, it had a protective tendency (Table 5). ...
Objective
To identify the obesity diagnosis with the highest association with physical frailty associated with sarcopenia EWGSOP II (sarcopenic obesity).
Subjects and methods
We performed a cross-sectional analysis of 371 community-dwelling older adults. Appendicular skeletal lean mass and total body fat (TBF) were assessed using dual-energy x-ray absorptiometry, and physical frailty was defined using Fried's criteria. The phenotypes were identified according to the presence of sarcopenia by EWGSOP II and obesity, which was diagnosed using two concepts: BMI obesity (BMI ≥ 30 kg/m²) and TBF obesity (percentage of TBF ≥ 35% for women and ≥ 25% for men). Finally, the association of each group with physical frailty was evaluated.
Results
The mean age was 78.15 ± 7.22 years. Sarcopenia EWGSOP II was diagnosed in 19.8% (n = 73), body mass index obesity was identified in 21.8% (n = 81), TBF obesity was identified in 67.7% (n = 251), and physical frailty was identified in 38.5% (n = 142). In a regression analysis for frailty, sarcopenic TBF obesity presented an odds ratio of 6.88 (95% confidence interval 2.60-18.24; p < 0.001).
Conclusion
In older Brazilian adults, sarcopenic obesity diagnosed by TBF obesity has a robust association with frailty and is independent of body mass index.
Keywords
Sarcopenia; frailty; obesity; elderly
... Mas ainda não há consenso sobre o significado desse efeito, Kosmiski et al (2008) sugere que os níveis de leptina não dependem da forma de lipodistrofia, mas sim da adiposidade total. Sob outra perspectiva, Langkilede et al (2015), discute a possibilidade do subgrupo de SLHIV com liphipertrofia (forma mista e lipohipertrófica) possuir, na verdade, um estado de resistência à leptina e, por isso, seus níveis relativamente maiores. ...
... Além disso, já é conhecida a interferência da leptina na resistência à insulina (BRUDER-NASCIMENTO, 2019) e estudos mostram que a resistência desses dois hormônios ocorre de maneira conjunta (LANGKILEDE et al. 2015;SRDIC et al, 2017). No entanto, não foi encontrada essa relação em nosso estudo. ...
People with HIV Lipodystrophy Syndrome may experience disturbance in leptin levels. This hormone is associated with non-alcoholic liver steatosis and endocrine-metabolic changes. The objective of this study was to evaluate the association between hepatic steatosis, leptin levels and clinical forms of Lipodystrophy. This is a cross-sectional study, conducted with 62 patients with Lipodystrophy using antiretroviral therapy (ART). The variables studied were anthropometry, laboratory tests and clinical data. Regarding the patients diagnosed with hepatic steatosis, 92% (n = 23) had a mixed or hypertrophic form (p = 0.02). Patients with hepatic steatosis had higher levels of leptin, insulin and HOMA IR, compared to those without steatosis. The correlation between leptin, insulin and body fat was not significant in this series (p> 0.05). There was no correlation between the duration of ART use and hepatic steatosis (p = 0.76). The classes most associated with steatosis were nucleoside analog reverse transcriptase inhibitors and protease inhibitors. Zidovudine was present in 20% (n = 5) of the cases with steatosis and 2.7% (n = 1) of the cases without steatosis. Patients with lipohypertrophy had higher levels of leptin and a higher prevalence of hepatic steatosis. Patients with hepatic steatosis had significantly higher leptin levels.
... 12 Inflammation has been implicated in the development of sarcopenia in PWH. 13 Thus, sarcopenia remains a clinical target of interest given its associated risk for accelerated aging in PWH and subsequent morbidity. ...
Background:
We have previously shown that initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation.
Methods:
ART-naïve PWH were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal Computed Tomography (CT) scans from baseline and week 96 were re-analyzed for psoas density and area and correlations explored with inflammation (IL-6, hs-CRP) and immune activation (sCD14, sCD163, %CD38+HLADR+ on CD4+ or CD8+ T-cells).
Results:
222 participants had available inflammation/immune activation markers and paired CT scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r -0.26, p<0.001) and sCD163 (r -0.15, p=0.03) and lower lean psoas area correlated with higher IL-6, hs-CRP, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T-cells (r= -0.30 to 0.13); all p≤0.05). From baseline to week 96, greater % decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r -0.14; p=0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T-cells (r -0.15 to -0.18; all p<0.04).
Conclusions:
Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.
... In contrast, other authors verified that although inflammatory mediators (i.e., soluble CD14, CRP, and IL-6) and immunosenescent phenotype (by CD57 + ) were high in PLWH than HIV-uninfected subjects, none of these biomarkers were associated with physical performance in 21 years old (54-69 years) PLWH under ART 19 . Langkilde et al. (2015) 20 verified that IL-6 and soluble urokinase plasminogen activator receptor were significantly associated with low muscle mass index. Recently, de Almeida et al. ...
... In contrast, other authors verified that although inflammatory mediators (i.e., soluble CD14, CRP, and IL-6) and immunosenescent phenotype (by CD57 + ) were high in PLWH than HIV-uninfected subjects, none of these biomarkers were associated with physical performance in 21 years old (54-69 years) PLWH under ART 19 . Langkilde et al. (2015) 20 verified that IL-6 and soluble urokinase plasminogen activator receptor were significantly associated with low muscle mass index. Recently, de Almeida et al. ...
The epidemiological profile of people living with HIV (PLWH) has expressively changed since the introduction of antiretroviral therapy (ART), from a high mortality rate to a profile similar to those living with chronic diseases. Despite the advances and effectiveness of ART, there are still various challenges to overcome, and we highlight the increased risk of sarcopenia in PLWH. This review study aims to (i) explore the pathophysiological background of sarcopenia in PLWH under the different existing ART and (ii) develop a mini-systematic review searching epidemiological studies investigating sarcopenia prevalence in PLWH. As our main findings: we established the risk of sarcopenia development, under a sequential path involving HIV, ART, immune activation, low-grade systemic inflammation, metabolic disorders, and changes in protein synthesis and breakdown in skeletal muscle tissue; some ART drugs, mainly reverse transcriptase inhibitors and protease inhibitors, contribute to critical metabolic changes, lowering the autophagy, increasing mitochondrial dysfunction and insulin resistance, which favor the development of inflammation and muscle protein breakdown. There is still insufficient data to discuss the effects of the new generation drugs, namely integrase inhibitors and fusion inhibitors, on skeletal muscle. More studies are needed to better clarify these relationships.
... In the Patient group, cognitive function was assessed using the 6-item short orientation memory concentration test (OMCT) at all time points (41). Furthermore, cognition was assessed using the Mini-Mental State Examination (MMSE) (42), and the trail making test A (TMT-A) and B (TMT-B) (43) for Patients (at 30-day and 1-year follow-up) and their age-matched Controls (at inclusion and 1-year follow-up). ...
Growth differentiation factor 15 (GDF15) is a stress-induced cytokine. Its plasma levels increase during aging and acute illness. In older Patients and age-matched Controls, we evaluated whether GDF15 levels (i) were associated with recovery after acute illness, and (ii) reflected different trajectories of aging and longitudinal changes in health measures. Fifty-two older Patients (≥65 years) were included upon admission to the Emergency Department (ED). At 30 days after discharge (time of matching), Patients were matched 1:1 on age and sex with Controls who had not been hospitalized within two years of inclusion. Both groups were followed up after 1 year. We assessed plasma levels of GDF15 and inflammatory biomarkers, frailty, nutritional status (mini nutritional assessment short-form), physical and cognitive function, and metabolic biomarkers. In Patients, elevated GDF15 levels at ED admission were associated with poorer resolution of inflammation (soluble urokinase plasminogen activator receptor, suPAR), slowing of gait speed, and declining nutritional status between admission and 30-day follow-up. At time of matching, Patients were frailer and overall less healthy than age-matched Controls. GDF15 levels were significantly associated with participant group, on average Patients had almost 60% higher GDF15 than age-matched Controls, and this difference was partly mediated by reduced physical function. Increases in GDF15 levels between time of matching and 1-year follow-up were associated with increases in levels of interleukin-6 in Patients, and tumor necrosis factor-α and suPAR in age-matched Controls. In older adults, elevated GDF15 levels were associated with signs of accelerated aging and with poorer recovery after acute illness.
... 61 In one study, suPAR was associated with low muscle mass, while IL-6 was associated with low muscle mass and increased fat mass in both patients and healthy controls. 62 Thus, there seem to be distinct inflammatory processes occurring simultaneously with different effects on muscle mass and fat mass, respectively. ...
Introduction
Sarcopenia is generally used to describe the age-related loss of muscle mass and strength believed to play a major role in the pathogenesis of physical frailty and functional impairment that may occur with old age. The knowledge surrounding the prevalence and determinants of sarcopenia in older medical patients is scarce, and it is unknown whether specific biomarkers can predict physical deconditioning during hospitalisation. We hypothesise that a combination of clinical, functional and circulating biomarkers can serve as a risk stratification tool and can (i) identify older acutely ill medical patients at risk of prolonged hospital stays and (ii) predict changes in muscle mass, muscle strength and function during hospitalisation.
Method and analysis
The Copenhagen PROTECT study is a prospective cohort study consisting of acutely ill older medical patients admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. Assessments are performed within 24 hours of admission and include blood samples, body composition, muscle strength, physical function and questionnaires. A subgroup of patients transferred to the Geriatric Department are included in a smaller geriatric cohort and have additional assessments at discharge to evaluate the relative change in circulating biomarker concentrations, body composition, muscle strength and physical function during hospitalisation. Enrolment commenced 4 November 2019, and proceeds until August 2021.
Ethics and dissemination
The study protocol has been approved by the local ethics committee of Copenhagen and Frederiksberg (H-19039214) and the Danish Data Protection Agency (P-2019-239) and all experimental procedures were performed in accordance with the Declaration of Helsinki. Findings from the project, regardless of the outcome, will be published in relevant peer-reviewed scientific journals in online ( www.clinicaltrials.gov ).
Trial registration number
NCT04151108
... Currently, the research with PLWHA has focused on chronic non-communicable diseases (Eyawo et al., 2017) and their adverse effects. PLWHA are still prone to morbidity associated with the use of cART, such as the cachexia syndrome (Scherzer et al., 2011) or sarcopenia (Langkilde et al., 2015) for example. As a consequence of these morbidities, there are marked reductions in skeletal muscle tissue (SMT), muscle strength (MS) and functional capacity, leading to a significant weakness (Erlandson et al., 2013). ...
The aim of the study was to compare the impact of 12-week resistance training with blood flow restriction (GRTBFR) versus, traditional resistance training (GTRT) and non-training on the muscle strength and body composition HIV/AIDS participants. Muscle strength was tested at baseline, and on the 6th, 21st and 36th training sessions, using maximal repetition test. Pre- and post-intervention body composition changes were measured by dual energy X-ray absorptiometry. Resistance-training was undertaken three times a week comprising bilateral elbow extension and flexion exercises, unilateral flexion and bilateral knee extension. Changes in strength and body composition (pre- and post-intervention) between groups were evaluated by mixed models of repeated measures, and by paired and unpaired comparisons, considering the Effect Size. All groups were similar at baseline for muscle strength and body composition. Post intervention, the training groups showed similar, statistically significant increases in muscle strength (GRTBFR=25.7 to 57.4%; GTRT=24.5 to 52.3%) and skeletal muscle tissue (GRTBFR=8.4%; GTRT=8.3%). There was also significant change in body fat (p=0.023 to 0.043), with significant effect sizes for strength and skeletal muscle tissue (0.41 to 2.27), respectively. These results suggest that both resistance training interventions promoted muscle hypertrophy, body fat reduction and positive impact on muscle strength in people living with HIV/AIDS. Resistance training with blood flow restriction proved to be an effective alternative to include patients with marked physical weakness, unable to engage in regular strength training program.
Trial registration: ClinicalTrials.gov identifier: NCT02783417..
... 23 Herein, we report that levels of plasma suPAR, the circulating form of uPAR, a measure of systemic inflammation and immune activation, 7 are also higher in women, even after adjusting for demographics, risk factors, medication use, and systemic inflammation measured as circulating hsCRP levels. Previous studies have shown that visceral adiposity is associated with higher suPAR levels, 33,34 and we observed that the association of female sex with suPAR was slightly attenuated but remained significant after adjusting for visceral adiposity measures. ...
Background
Women have higher circulating levels of soluble urokinase‐type plasminogen activator receptor (suPAR), and elevated suPAR is associated with cardiovascular risk. The independent association of sex with suPAR and the impact of sex on its association with cardiovascular risk are unknown.
Methods and Results
Plasma suPAR was measured using ELISA in 2 cohorts of 666 asymptomatic individuals (49 years, 65% women) and 4184 patients with coronary artery disease (63 years, 37% women). Independent association of sex with suPAR was studied using linear regression models adjusted for demographics, risk factors, and visceral adiposity in asymptomatic participants. Impact of sex on association of suPAR with all‐cause mortality was studied in patients with coronary artery disease using multivariable‐adjusted Cox models. Sex‐specific suPAR cutoffs for predicting all‐cause mortality were calculated. Asymptomatic women had 10% higher suPAR compared with men after adjusting for confounders, and visceral adiposity partly accounted for this association. Over a median follow‐up of 5.2 years, 795 deaths were recorded in patients with coronary artery disease. Log 2 ‐transformed suPAR was independently associated with mortality (hazard ratio per 1‐SD 1.72, 95% CI 1.60–1.85) and an interaction with sex was noted ( P =0.005). Association of suPAR with mortality was slightly weaker in women (hazard ratio 1.61, 95% CI 1.41–1.83) compared with men (hazard ratio 1.83, 95% CI 1.67–2.00). However, using sex‐specific suPAR cut‐offs (4392 pg/mL for women and 3187 pg/mL for men), a similar mortality incidence was observed for both sexes (38.5% and 35.5%, respectively, P =0.3).
Conclusions
Women have 10% higher plasma suPAR levels compared with men. Elevated sex‐specific plasma suPAR levels are equally predictive of risk of adverse events in both sexes.
