RSS-Feed abonnieren
DOI: 10.1055/s-0032-1306342
Altered Response to Neuroendocrine Challenge Linked to Indices of the Metabolic Syndrome in Healthy Adults
Publikationsverlauf
received 17. Oktober 2011
accepted 22. Februar 2012
Publikationsdatum:
27. April 2012 (online)
![](https://www.thieme-connect.de/media/hmr/201207/lookinside/thumbnails/10.1055-s-0032-1306342-1.jpg)
Abstract
Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin resistance, and hypercholesterolemia. Hypothalamic-pituitary-adrenal (HPA) axis activity is frequently abnormal in MetS, and excessive cortisol exposure may be implicated in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic hormone (ACTH) responses to a standardized neuroendocrine challenge test would be associated with indices of MetS in a community sample of healthy adults. Healthy adults, 125 men and 170 women, without significant medical problems or chronic medications were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their history of early life stress and recent stress, as well as mood and anxiety symptoms. Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures of central adiposity (p<0.001) and blood pressure (p<0.01), and positively associated with HDL cholesterol (p<0.01). These findings remained significant after controlling for body mass index (BMI). Measures of stress and anxiety and depressive symptoms were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but were not related to MetS indices. That altered HPA axis function is linked to MetS components even in a healthy community sample suggests that these processes may be involved in the pathogenesis of MetS. Identification of premorbid risk processes might allow for detection and intervention prior to the development of disease.
-
References
- 1 Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab 2009; 94: 2692-2701
- 2 Morton NM. Obesity and corticosteroids: 11beta-hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease. Mol Cell Endocrinol 2010; 316: 154-164
- 3 Rosmond R. Role of stress in the pathogenesis of the metabolic syndrome. Psychoneuroendocrinology 2005; 30: 1-10
- 4 Duclos M, Marquez Pereira P, Barat P, Gatta B, Roger P. Increased cortisol bioavailability, abdominal obesity, and the metabolic syndrome in obese women. Obes Res 2005; 13: 1157-1166
- 5 Filipovsky J, Ducimetiere P, Eschwege E, Richard JL, Rosselin G, Claude JR. The relationship of blood pressure with glucose, insulin, heart rate, free fatty acids and plasma cortisol levels according to degree of obesity in middle-aged men. J Hypertens 1996; 14: 229-235
- 6 Lasikiewicz N, Hendrickx H, Talbot D, Dye L. Exploration of basal diurnal salivary cortisol profiles in middle-aged adults: associations with sleep quality and metabolic parameters. Psychoneuroendocrinology 2008; 33: 143-151
- 7 Ljung T, Andersson B, Bengtsson BA, Bjorntorp P, Marin P. Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution: a dose-response study. Obes Res 1996; 4: 277-282
- 8 Ljung T, Holm G, Friberg P, Andersson B, Bengstson BA, Svensson J, Dallman M, McEwen B, Bjorntorp P. The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men. Obes Res 2000; 8: 487-495
- 9 Marniemi J, Kronholm E, Aunola S, Toikka T, Mattlar CE, Koskenvuo M, Ronnemaa T. Visceral fat and psychosocial stress in identical twins discordant for obesity. J Intern Med 2002; 251: 35-43
- 10 Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, Johnson O, Walker BR. Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 2001; 86: 1418-1421
- 11 Rutters F, Nieuwenhuizen AG, Lemmens SG, Born JM, Westerterp-Plantenga MS. Hypothalamic-pituitary-adrenal (HPA) axis functioning in relation to body fat distribution. Clin Endocrinol 2010; 72: 738-743
- 12 Ward AM, Syddall HE, Wood PJ, Dennison EM, Phillips DI. Central hypothalamic-pituitary-adrenal activity and the metabolic syndrome: Studies using the corticotrophin-releasing hormone test. Metabolism 2004; 53: 720-726
- 13 Pasquali R, Cantobelli S, Casimirri F, Capelli M, Bortoluzzi L, Flamia R, Labate AM, Barbara L. The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution. J Clin Endocrinol Metab 1993; 77: 341-346
- 14 Ward AM, Fall CH, Stein CE, Kumaran K, Veena SR, Wood PJ, Syddall HE, Phillips DI. Cortisol and the metabolic syndrome in South Asians. Clin Endocrinol 2003; 58: 500-505
- 15 Brunner EJ, Hemingway H, Walker BR, Page M, Clarke P, Juneja M, Shipley MJ, Kumari M, Andrew R, Seckl JR, Papadopoulos A, Checkley S, Rumley A, Lowe GD, Stansfeld SA, Marmot MG. Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study. Circulation 2002; 106: 2659-2665
- 16 Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P. Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism 1992; 41: 882-886
- 17 Misra M, Bredella MA, Tsai P, Mendes N, Miller KK, Klibanski A. Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab 2008; 295: E385-E392
- 18 Sen Y, Aygun D, Yilmaz E, Ayar A. Children and adolescents with obesity and the metabolic syndrome have high circulating cortisol levels. Neuro Endocrinol Lett 2008; 29: 141-145
- 19 Steptoe A, Kunz-Ebrecht SR, Brydon L, Wardle J. Central adiposity and cortisol responses to waking in middle-aged men and women. Int J Obes Relat Metab Disord 2004; 28: 1168-1173
- 20 Weigensberg MJ, Toledo-Corral CM, Goran MI. Association between the metabolic syndrome and serum cortisol in overweight Latino youth. J Clin Endocrinol Metab 2008; 93: 1372-1378
- 21 Reinehr T, Andler W. Cortisol and its relation to insulin resistance before and after weight loss in obese children. Horm Res 2004; 62: 107-112
- 22 Phillips DI, Barker DJ, Fall CH, Seckl JR, Whorwood CB, Wood PJ, Walker BR. Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome?. J Clin Endocrinol Metab 1998; 83: 757-760
- 23 Rosmond R, Dallman MF, Bjorntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 1998; 83: 1853-1859
- 24 Kirschbaum C, Pirke KM, Hellhammer DH. The ‘Trier Social Stress Test’ – a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993; 28: 76-81
- 25 Epel ES, McEwen B, Seeman T, Matthews K, Castellazzo G, Brownell KD, Bell J, Ickovics JR. Stress and body shape: stress-induced cortisol secretion is consistently greater among women with central fat. Psychosom Med 2000; 62: 623-632
- 26 Mujica-Parodi LR, Renelique R, Taylor MK. Higher body fat percentage is associated with increased cortisol reactivity and impaired cognitive resilience in response to acute emotional stress. Int J Obs 2009; 33: 157-165
- 27 Wallerius S, Rosmond R, Ljung T, Holm G, Bjorntorp P. Rise in morning saliva cortisol is associated with abdominal obesity in men: a preliminary report. J Endocrinol Invest 2003; 26: 616-619
- 28 Bengtsson I, Lissner L, Ljung T, Rosengren A, Thelle D, Wahrborg P. The cortisol awakening response and the metabolic syndrome in a population-based sample of middle-aged men and women. Metabolism 2010; 59: 1012-1019
- 29 Pasquali R, Ambrosi B, Armanini D, Cavagnini F, Uberti ED, Del Rio G, de Pergola G, Maccario M, Mantero F, Marugo M, Rotella CM, Vettor R. Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study. J Clin Endocrinol Metab 2002; 87: 166-175
- 30 Kopelman PG, Grossman A, Lavender P, Besser GM, Rees LH, Coy D. The cortisol response to corticotrophin-releasing factor is blunted in obesity. Clin Endocrinol 1988; 28: 15-18
- 31 Trainer PJ, Faria M, Newell-Price J, Browne P, Kopelman P, Coy DH, Besser GM, Grossman AB. A comparison of the effects of human and ovine corticotropin-releasing hormone on the pituitary-adrenal axis. J Clin Endocrinol Metab 1995; 80: 412-417
- 32 Solano MP, Kumar M, Fernandez B, Jones L, Goldberg RB. The pituitary response to ovine corticotropin-releasing hormone is enhanced in obese men and correlates with insulin resistance. Horm Res 2001; 33: 39-43
- 33 Katz JR, Taylor NF, Goodrick S, Perry L, Yudkin JS, Coppack SW. Central obesity, depression and the hypothalamo-pituitary-adrenal axis in men and postmenopausal women. Int J Obes Relat Metab Disord 2000; 24: 246-251
- 34 Pasquali R, Anconetani B, Chattat R, Biscotti M, Spinucci G, Casimirri F, Vicennati V, Carcello A, Labate AM. Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress. Metabolism 1996; 45: 351-356
- 35 Epel ES. Psychological and metabolic stress: a recipe for accelerated cellular aging?. Hormones 2009; 8: 7-22
- 36 Folsom AR, Kuba K, Leupker RV, Jacobs DR, Frantz Jr ID. Lipid concentrations in serum and EDTA-treated plasma from fasting and nonfasting normal persons, with particular regard to high-density lipoprotein cholesterol. Clin Chem 1983; 29: 505-508
- 37 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539-553
- 38 Tyrka AR, Wier LM, Anderson GM, Wilkinson CW, Price LH, Carpenter LL. Temperament and response to the Trier Social Stress Test. Acta Psychiatrica Scandinavica 2007; 115: 395-402
- 39 Carpenter LL, Tyrka AR, Ross NS, Khoury L, Anderson GM, Price LH. Effect of childhood emotional abuse and age on cortisol responsivity in adulthood. Biol Psychiatry 2009; 66: 69-75
- 40 Inder WJ, Obeyesekere VR, Alford FP, Jang C. Skeletal muscle 11HSD1β activity of nondiabetic subjects is unaltered in central obesity-associated insulin resistance. Horm Metab Res 2011; 43: 257-260
- 41 Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry 2003; 160: 1554-1565
- 42 Carpenter LL, Carvalho JP, Tyrka AR, Wier LM, Mello AF, Mello MF, Anderson GM, Wilkinson CW, Price LH. Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biol Psychiatry 2007; 62: 1080-1087
- 43 Carpenter LL, Tyrka AR, McDougle CJ, Malison RT, Owens MJ, Nemeroff CB, Price LH. Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects. Neuropsychopharmacology 2004; 29: 777-784
- 44 Elzinga BM, Roelofs K, Tollenaar MS, Bakvis P, van Pelt J, Spinhoven P. Diminished cortisol responses to psychosocial stress associated with lifetime adverse events a study among healthy young subjects. Psychoneuroendocrinology 2008; 33: 227-237
- 45 Tyrka AR, Wier L, Price LH, Ross N, Anderson GM, Wilkinson CW, Carpenter LL. Childhood parental loss and adult hypothalamic-pituitary-adrenal function. Biol Psychiatry 2008; 63: 1247-1254
- 46 Klaassens ER, van Noorden MS, Giltay EJ, van Pelt J, van Veen T, Zitman FG. Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 889-894
- 47 Danese A, Moffitt TE, Harrington H, Milne BJ, Polanczyk G, Pariante CM, Poulton R, Caspi A. Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolesc Med 2009; 163: 1135-1143