 |
|
|
| |
Inflammatory biomarkers, adipokines and longitudinal changes in gait speed and fatigue in men with or at risk for HIV infection
|
| |
| |
Reported by Jules Levin
20th International Workshop on Comorbidities and Adverse Drug Reactions in HIV
Oct 13-14 2018 NYC
Jing Sun, Todd T. Brown, Joseph B. Margolick, Susheel P. Patil, Alan Schwartz, Kristine Erlandson, Philip Smith, Naresh M. Punjabi,
Jennifer Schrack
In conclusion, we observed that HIV+ men showed increased level of several inflammatory markers compared to the epidemiologically similar HIV- men. The difference of the inflammatory markers has a significant trend by HIV-, HIV+ with ttreatment, and HIV+ without treatment, again suggesting the importance of early ART initiation.
We observed that Serum leptin was significantly associated with increased odds of fatigue, while proinflammatory cytokines (sTNF-receptor 1, and inflammatory index) were significantly associated with slower gait speed. This findings might suggest different mechanisms may be contributing to fatigue and physical function decline with aging among PLWH.
https://en.wikipedia.org/wiki/Leptin ---- Leptin (from Greek λεϖτσς leptos, "thin"), "the hormone of energy expenditure",[a] is a hormone predominantly made by adipose cells that helps to regulate energy balance by inhibiting hunger. Leptin is opposed by the actions of the hormone ghrelin, the "hunger hormone". Both hormones act on receptors in the arcuate nucleus of the hypothalamus.[6] In obesity, a decreased sensitivity to leptin occurs (similar to insulin resistance in type 2 diabetes), resulting in an inability to detect satiety despite high energy stores and high levels of leptin.[7]
Although regulation of fat stores is deemed to be the primary function of leptin, it also plays a role in other physiological processes, as evidenced by its many sites of synthesis other than fat cells, and the many cell types beside hypothalamic cells that have leptin receptors. Many of these additional functions are yet to be defined.[8][9][10][11][12][13]
program abstract
Background: People living with HIV (PLWH) may experience more debilitating symptoms (for example, frailty) and faster physical function decline compared to people without HIV infection (PWOH). Fatigue and gait speed are components of the physical frailty phenotype, which are hypothesized to be associated with chronic inflammation among PLWH. Previous studies suggested that serum adipokine (for example, leptin) levels and inflammatory biomarkers are associated with fatigue and functional decline through adverse changes in energy metabolism and oxidative stress. This study sought to evaluate the associations among adipokine and cytokine biomarkers and two markers of physical function (fatigue and gait speed) among men with and without HIV infection.
Materials and methods: Participants in the Baltimore/ Washington site of the Multicenter AIDS Cohort Study (MACS) were recruited to participate in the study and stratified by HIV serostatus and antiretroviral treatment: HIV-, HIV+ without HAART and HIV+ with HAART. Gait speed was assessed semi-annually in metres per second over a 4-metre course and self reported fatigue in the past 3 days was collected via questionnaire. Inflammatory cytokines (IL1-b, IL6, IL8, TNF-α, sTNF-receptor 1 and sTNF-receptor 2), C-reactive protein (CRP), and serum levels of leptin, leptin soluble receptor and adiponectin were measured using enzyme-linked immunosorbent assay at baseline.
The inflammatory index was calculated as the sum of 1/3 log of IL6 and 2/3 log of sTNF-receptor 1. Logistic regression models were used to assess the association between biomarkers and fatigue at baseline, and mixed linear regression models were used to assess association between the biomarkers at baseline and the rate of gait speed decline over time.
Results: 158 men, 98 PLWH and 60 PWOH, contributed 1,214 person-years over a median of 8.8 years of follow-up. Among PLWH, 64% were on HAART at baseline and 90% achieved viral suppression in followup visits. The median age at baseline was 53 and PWOH were 5 years older than PLWH (P<0.02). Among all participants, 56% were Black, 68% had some college education and 55% were overweight (BMI ≥25). There was an upward trend in level of IL8 (P<0.01), TNF-α (P<0.01) and sTNF-receptor 2 (P<0.01) at baseline by PWOH, PLWH on HAART and PLWH without HAART. After controlling for covariates (age, race, BMI, college education, and HIV and HAART), every unit increase in serum leptin was associated with 92% increased odds (95% CI: 1.10, 3.38) of self-reported fatigue. Higher levels of sTNF-receptor 1 and the inflammatory index were associated with slower gait speed (every unit increase in the measurements associated with 0.07 metre/second/year [95% CI: -0.13, -0.01] decline and 0.065 metre/second/year [95% CI: -0.12, -0.01] decline in gait speed, respectively) after controlling for covariates.
Conclusions: In a sample of HIV-infected men with and without HAART and demographically and behaviorally similar HIV-uninfected men, serum leptin was significantly associated with increased odds of fatigue, while proinflammatory cytokines (sTNF-receptor 1, and inflammatory index) was significantly associated with slower gait speed. These results suggest that different mechanisms may be contributing to fatigue and physical function decline with ageing.
Accelerated functional decline and higher prevalence of frailty among PLWHIV have been observed compared to HIV-uninfected controls. Understanding the pathophysiology of this functional disparities is important to the development of long-term treatment to improve quality of life among people aging with HIV. Frailty has been strongly associated with major adverse clinical outcomes, including hospitalization, institutionalization, disability, and premature death. Marker of inflammation have been linked to frailty and mortality among PLWH.
Although frailty has been described as a phenotype, which typically measured by a validated five criteria, including slow gait, decreased grip strength, exhaustion or fatigue, low physical activity, and weight loss, different mechanisms could contribute to each individual phenotypic criteria.
|
| |
|
|
|
|
|
