Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women
ABSTRACT Objectives: Frailty status is associated with altered glucose-insulin dynamics. Here, we sought to investigate whether alteration in the dynamics of other circulating energy metabolism hormones after oral glucose is associated with frailty status. Design: Substudy of older women in a prospective cohort. Setting: Baltimore, Maryland. Participants: Seventy-three community-dwelling women aged 84-95 years without a diagnosis of diabetes who were enrolled in the Women's Health and Aging Study II. Measurements: We examined stimulus-response dynamics of free fatty acids (FFA), gut- (ghrelin,GLP-1) and adipocyte-derived hormones (leptin, adiponectin, resistin), growth hormone (GH), insulin-like growth factor 1 (IGF-1), and interleukin-6 (IL-6) at 0, 30, 60, 120, and 180-minutes after a 75-g glucose challenge according to frailty status (non-frail, pre-frail, or frail). Results: On average, frail women had higher fasting levels of glucose-raising hormones (FFA, resistin, GH, and IL-6) and lower fasting levels of glucose-lowering hormones (ghrelin, adiponectin, GLP-1 and IGF-1) versus non-frail women but these results were not statistically significant. Frail women also had higher fasting levels of leptin with relative adiposity compared to their counterparts, suggestive of leptin-resistance. Integrated area under the curve (AUC) values for each hormone followed similar trends by frailty status. After age and BMI adjustment, frail versus non-frail women were more likely to be in the lowest tertile of fasting ghrelin levels and 120-min ghrelin levels (both p<0.05) in logistic regression analyses. No large differences were found for other hormones in adjusted models. Conclusions: Our findings suggest dysregulation of the orexigenic hormone ghrelin in the frailty syndrome. Further studies are needed to explore the role of ghrelin dysregulation in the clinical manifestation of frailty.
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ABSTRACT: Frailty is an important geriatric syndrome. Adiponectin is an important adipokine that regulates energy homeostasis. The aim of this study is to investigate the relationship between plasma adiponectin levels and frailty in elders. The demographic data, body weight, metabolic and inflammatory parameters, including plasma glucose, total cholesterol, triglyceride, tumor necrosis factor alpha (TNF-α), c-reactive protein (CRP) and adiponectin levels, were assessed. The frailty score was assessed using the Fried Frailty Index (FFI). The mean (SD) age of the 168 participants [83 (49.4%) men and 85 (50.6%) women] was 76.86 (6.10) years. Judged by the FFI score, 42 (25%) elders were robust, 92 (54.7%) were pre-frail, and 34 (20.3%) were frail. The mean body mass index was 25.19 (3.42) kg/m(2). The log-transformed mean (SD) plasma adiponectin (µg/mL) level was 1.00 (0.26). The log-transformed mean plasma adiponectin (µg/mL) levels were 0.93 (0.23) in the robust elders, 1.00 (0.27) in the pre-frail elders, and 1.10 (0.22) in the frail elders, and the differences between these values were statistically significant (p = 0.012). Further analysis showed that plasma adiponectin levels rose progressively with an increasing number of components of frailty in all participants as a whole (p for trend = 0.024) and males (p for trend = 0.037), but not in females (p for trend = 0.223). Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders. The difference between the sexes suggests that certain sex-specific mechanisms may exist to affect the association between adiponectin levels and frailty.PLoS ONE 02/2013; 8(2):e56250. DOI:10.1371/journal.pone.0056250 · 3.53 Impact Factor
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ABSTRACT: Background:Acyl-ghrelin is thought to have both orexigenic effects and to stimulate growth hormone (GH) release. A possible cause of the anorexia of aging is an age-dependent decrease in circulating acyl-ghrelin levels.Objectives:The purpose of the study was to compare acyl-ghrelin and GH concentrations between healthy old and young adults and to examine the relationship of acyl-ghrelin and GH secretion in both age groups.Methods:Six healthy older adults (ages 62-74, BMI range 20.9 - 29 kg/m(2)) and eight healthy young men (ages 18-28, BMI range 20.6 - 26.2 kg/m(2)) had frequent blood samples drawn for hormone measurements every 10 min for 24 hr. Ghrelin was measured in an in-house two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in a sensitive assay (Immulite 2000) and GH peaks were determined by deconvolution analysis. The acyl-ghrelin/GH association was estimated from correlations between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-min interval preceding each GH burst.Results:24-h mean (± SEM) GH (0.48 ± 0.14 vs. 2.2 ± 0.3 μ g/L, p<0.005) and acyl-ghrelin (14.7 ± 2.3 vs. 27.8 ± 3.9 pg/mL, p<0.05) levels were significantly lower in older adults compared to young. 24-h cortisol concentrations were higher in the old than the young (15.1 ± 1.0 vs. 10.6 ± 0.9 μ g/dL, respectively), p<0.01. The ghrelin/GH association was more than 3-fold lower in the older group compared to the young adults (0.16 ± 0.12 vs. 0.69 ± 0.04), p<0.001.Conclusions:These results provide further evidence of an age-dependent decline in circulating acyl-ghrelin levels, which might play a role both in the decline of GH and in the anorexia of aging. Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are less tightly linked to GH regulation.The Journal of Clinical Endocrinology and Metabolism 02/2014; 99(2):602-608. DOI:10.1210/jc.2013-3158 · 6.31 Impact Factor
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ABSTRACT: Frailty is an increasingly recognized syndrome resulting in age-related decline in function and reserve across multiple physiologic systems. It presents as a hyperinflammable state, characterized by high vulnerability for adverse health outcomes, such as disability, falls, hospitalization, institutionalization, and mortality. The prevalence of Frailty syndrome (FS) is of potentially enormous significance, as it affects 20-30% of adults older than 75. Cellular and molecular basis of frailty has not been elucidated. The objective of this review is to discuss recent advances in: (i) the potential cellular and molecular basis of Frailty syndrome, including development of new models to study it; (ii) the human and animal measures of Frailty syndrome; and (iii) the development of objective cross-species correlates to aid the understanding, diagnosis, treatment and rehabilitation of Frailty syndrome in older adults.Experimental gerontology 06/2014; 54. DOI:10.1016/j.exger.2014.01.024 · 3.53 Impact Factor