Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
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.
Substudy of older women in a prospective cohort.
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.
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).
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.
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.
- Morley JE. Anorexia of aging: physiologic and pathologic. Am J Clin Nutr. 1997;66:760–773.
- Boyd CM, Xue QL, Simpson CF, et al. Frailty, hospitalization, and progression of disability in a cohort of disabled older women. Am J Med 2005;118: 1225–1231. CrossRef
- Fried LP, Tangen CM, Walston J, et al.; Cardiovascular Health Study. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56: M146–M156. CrossRef
- Fried LP, Xue QL, Cappola AR, et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 2009;64: 1049–1057. CrossRef
- Cappola AR, Xue QL, Fried LP. Multiple hormonal deficiencies in anabolic hormones are found in frail older women. J Gerontol A Biol Sci Med 2009;64: 243–248. CrossRef
- Kalyani RR, Varadhan R, Weiss CO, Fried LP, Cappola AR. Frailty Status and Altered Glucose-Insulin Dynamics. J Gerontol A Biol Sci Med Sci. 2011 Aug 26. [Epub ahead of print]
- Walston J, McBurnie MA, Newman A, et al.; Cardiovascular Health Study. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 2002;162: 2333–2341.
- Blaum CS, Xue QL, Tian J, Semba RD, Fried LP, Walston J. Is hyperglycemia associated with frailty status in older women? J Am Geriatr Soc 2009;57: 840–847. CrossRef
- Barzilay JI, Blaum C, Moore T, et al. Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med 2007;167: 635–641. CrossRef
- Goulet ED, Hassaine A, Dionne IJ, et al. Frailty in the elderly is associated with insulin resistance of glucose metabolism in the postabsorptive state only in the presence of increased abdominal fat. Exp Gerontol 2009;44: 740–744. CrossRef
- Arafat AM, Mohlig M, Weickert MO, Perschel FH, Purschwitz J, Spranger J, Strasburger CJ, Schofl C, Pfeiffer AF. Growth hormone response during oral glucose tolerance test: the impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls, and the role of gender, age, and body mass index. J Clin Endocrinol Metab. 2008;93:1254–1262. CrossRef
- Banerjee RR, Rangwala SM, Shapiro JS, et al. Regulation of fasted blood glucose by resistin. Science 2004;303: 1195–1198. CrossRef
- Boden G. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes. 2003;111: 121–124. CrossRef
- Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Op Lipid 2002;13: 51–59. CrossRef
- Clemmons DR. Role of IGF in maintaining normal glucose homeostasis. Horm Res 2004;62: 77–82. CrossRef
- Senn JJ, Klover PJ, Nowak IA, et al. IL-6 induces cellular insulin resistance in hepatocytes. Diabetes 2002;51: 3391–3399. CrossRef
- Rask E, Olsson T, Soderberg S, Johnson O, Seckl J, Hoist JJ, Ahren B; Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA). Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men. Diabetes Care. 2001;24: 1640–1645. CrossRef
- Serra-Prat M, Palomera E, Clave P, Puig-Domingo M. Effect of age and frailty on ghrelin and cholecystokinin responses to a meal test. Am J Clin Nutr 2009;89: 1410–1417 CrossRef
- Di Francesco V, Fantin F, Residori L, et al. Effect of age on the dynamics of acylated ghrelin in fasting conditions and in response to a meal. J Am Geriatr Soc 2008;56: 1369–1370. CrossRef
- Shiiya T, Nakazato M, Mizuta M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002;87: 240–244. CrossRef
- Van Hall, G, Steensberg A, Fischer C, et al. Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals. J Clin Endocrinol Metab 2008;7: 2851–2858. CrossRef
- DeBoer MD, Zhu XX, Levasseur P, et al. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology 2007;148: 3004–3012. CrossRef
- Goto M, Arima H, Watanabe M, Hayashi M, Banno R, Sato I, Nagasaki H, Oiso Y. Ghrelin increases neuropeptide Y and agouti-related peptide gene expression in the arcuate nucleus in rat hypothalamic organotypic cultures. Endocrinology. 2006;147: 5102–5109. CrossRef
- Payette C, Blackburn P, Lamarche B, et al. Sex differences in postprandial plasma tumor necrosis factor-alpha, interleukin-6, and C-reactive protein concentrations. Metabolism 2009;58: 1593–1601. CrossRef
- Cappola AR, Bandeen-Roche K, Wand GS, et al. Association of IGF-1 levels with muscle strength and mobility in older women. J Clin Endocrinol Metab 2001;86: 4139–4146. CrossRef
- Holness MJ, Hegazy S, Sugden MC. Signaling Satiety and Starvation to p-Cell Insulin Secretion. Curr Diabetes Rev. 2011 Sep 15. [Epub ahead of print]
- Fried LP, Bandeen-Roche K, Chaves PH, et al. Preclinical mobility disability predicts incident mobility disability in older women. J Gerontol A Biol Sci Med Sci 2000;55: M43–M52. CrossRef
- Bandeen-Roche K, Xue QL, Ferrucci L, et al. Phenotype of frailty: characterization in the women’s health and aging studies. J Gerontol A Biol Sci Med Sci 2006;61: 262–266. CrossRef
- Nanjo Y, Adachi H, Hirai Y, Enomoto M, Fukami A, Otsuka M, Yoshikawa K, Yokoi K, Ogata K, Tsukagawa E, Kasahara A, Murayama K, Yasukawa H, Kojima M, Imaizumi T. Factors associated with plasma ghrelin level in Japanese general population. Clin Endocrinol (Oxf). 2011;74:453–458. CrossRef
- Tai K, Visvanathan R, Hammond AJ, Wishart JM, Horowitz M, Chapman IM. Fasting ghrelin is related to skeletal muscle mass in healthy adults. Eur J Nutr 2009;48:176–183. CrossRef
- Gruendel S, Weickert MO, Garcia AL, Wagner K, Pfeiffer AF, Harsch I, Koebnick C. Serum resistin increases in a postprandial state during liquid meal challenge test in healthy human subjects. J Endocrinol Invest. 2006;29: RC27–RC30.
- Barkoukis H, Marchetti CM, Nolan B, Sistrun SN, Krishnan RK, Kirwan JP. A high glycemic meal suppresses the postprandial leptin response in normal healthy adults. Ann Nutr Metab. 2007;51: 512–518. CrossRef
- Hoffstedt J, Arvidsson E, Sjolin E, Wahlen K, Arner P. Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance. J Clin Endocrinol Metab. 2004; 891391-6.
- English PJ, Coughlin SR, Hayden K, et al. Plasma adiponectin increases postprandially in obese, but not in lean subjects. Obes Res 2003;11: 839–844. CrossRef
- Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature 2001;409: 307–312. CrossRef
- Makimura H, Stanley TL, Chen CY, Branch KL, Grinspoon SK. Relationship of adiponectin to endogenous GH pulse secretion parameters in response to stimulation with a growth hormone releasing factor. Growth Horm IGF Res. 2011;21: 155–159. CrossRef
- Frayn KN. Adipose tissue and the insulin resistance syndrome. Proc Nutr Soc. 2001;60: 375–380. CrossRef
- Kallio P, Kolehmainen M, Laaksonen DE, Pulkkinen L, Atalay M, Mykkanen H, Uusitupa M, Poutanen K, Niskanen L. Inflammation markers are modulated by responses to diets differing in postprandial insulin responses in individuals with the metabolic syndrome. Am J Clin Nutr. 2008;87:1497–1503.
- Wilson MM, Morley JE. Invited review: Aging and energy balance. J Appl Physiol 2003;95: 1728–1736.
- Bartali B, Frongillo EA, Bandinelli S, et al. Low nutrient intake is an essential component of frailty in older persons. J Gerontol A Biol Sci Med Sci 2006;61: 589–593. CrossRef
- Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women
The journal of nutrition, health & aging
Volume 16, Issue 8 , pp 679-686
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Division of Endocrinology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
- 6. 1830 East Monument Street, Suite 333, Baltimore, MD, 21287, USA
- 2. Division of Geriatric Medicine and Gerontology and Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
- 3. Division of Geriatric Medicine and Gerontology, College of Human Medicine of Michigan State University, Grand Rapids, USA
- 4. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
- 5. Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA