Horm Metab Res 2013; 45(03): 245-251
DOI: 10.1055/s-0032-1323741
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Altered Homeostasis of Systemic Glucocorticoids as Related to Obesity, Glucose Tolerance, and Smoking

H. H. Schäfer
1   Department for Anatomy II, Friedrich Schiller University, Jena, Germany
,
J. D. de Villiers
2   Faculty of Health Sciences, University of Stellenbosch, South Africa
,
E. Sivukhina
1   Department for Anatomy II, Friedrich Schiller University, Jena, Germany
,
J. Lewis
3   Department of Clinical Biochemistry, Canterbury Health Laboratories, Christchurch, New Zealand
,
D. Wande
4   STACS Statistical research and analysis, Cape Town, South Africa
,
B. Perembe
4   STACS Statistical research and analysis, Cape Town, South Africa
,
G. Jirikowski
1   Department for Anatomy II, Friedrich Schiller University, Jena, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 16. April 2012

accepted 06. August 2012

Publikationsdatum:
18. September 2012 (online)

Abstract

The hypothalamic-pituitary-adrenal axis is supposed to be involved in the pathogenesis of the metabolic disorders. Differences in adipose tissues and parameters of insulin resistance are linked to steroid homeostasis. We assessed the correlation of fat tissue distribution, gender, and glucose control with levels of systemic corticosteroid-binding globulin (CBG), free cortisol (FuF), and total cortisol (FuM). Data of 1 114 patients with overweight, lipid disorders, and impaired glucose tolerance were collected. Blood samples were sorted according to gender and anthropometric measures. Variable-association was calculated using the Spearman Rank Correlation coefficient and tested for significance (p<0.05 and p<0.01). CBG and FuF were consistently negatively correlated to each weight parameter. Especially in women, fat mass index (FMI) was significantly negatively correlated with CBG-levels. While CBG levels dropped with increasing age, FuF showed an inverse behavior. Glycohemoglobin levels showed negative correlations with CBG while fasting glucose did not. Both changes were associated with significant increases in FuF. All negative correlations to cortisol and its binding globulin with regards to weigh- and glucose-control parameters were absent in smokers compared to nonsmokers. Our observations suggest that different weight parameters correspond to adrenal steroids and their buffer systems. Especially in women, CBG levels might serve as prognostic marker for the fat mass. In addition, CBG levels may predict long term blood glucose control more reliably than FG. However, the value of CBG as an indirect surrogate-marker for obesity and glucose is limited in smokers.

 
  • References

  • 1 Gathercole LL, Morgan SA, Bujalska IJ, Hauton D, Stewart PM, Tomlinson JW. Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue. PLoS One 2011; 6: e26223
  • 2 Kyrou I, Tsigos C. Stress mechanisms and metabolic complications. Horm Metab Res 2007; 39: 430-438
  • 3 Engeli S, Schling P, Gorzelniak K, Boschmann M, Janke J, Ailhaud G, Teboul M, Massiera F, Sharma AM. The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?. Int J Biochem Cell Biol 2003; 35: 807-825
  • 4 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89: 2548-2556
  • 5 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
  • 6 Rutters F, Nieuwenhuizen AG, Lemmens SG, Bouwman F, Mariman E, Westerterp-Plantenga MS. Associations between anthropometrical measurements, body composition, single-nucleotide polymorphisms of the hypothalamus/pituitary/adrenal (HPA) axis and HPA axis functioning. Clin Endocrinol (Oxf) 2011; 74: 679-686
  • 7 Patel SB, Reams GP, Spear RM, Freeman RH, Villarreal D. Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease. Curr Hypertens Rep 2008; 10: 131-137
  • 8 Alvarez-Castro P, Sangiao-Alvarellos S, Brandon-Sanda I, Cordido F. Endocrine function in obesity. Endocrinol Nutr 2011; 58: 422-432
  • 9 Malendowicz LK, Gorska T, Tortorella C, Nowak M, Majchrzak M, Spinazzi R, Nussdorfer GG, Nowak KW. Acute in vivo effects of leptin and leptin fragments on corticosteroid hormone secretion and entero-insular axis in the rat. Int J Mol Med 2004; 13: 829-834
  • 10 Vila R, Gutierrez R, Luisa Granada M, Maria Masanes R, del Mar Grasa M, Antonio Fernandez Lopez J, Remesar X, Formiguera X, Foz M, Alemany M. Hormonal alterations on young morbid obese women. Med Clin. (Barc); 2001. 116. 321-323
  • 11 Manco M, Fernandez-Real JM, Valera-Mora ME, Dechaud H, Nanni G, Tondolo V, Calvani M, Castagneto M, Pugeat M, Mingrone G. Massive weight loss decreases corticosteroid-binding globulin levels and increases free cortisol in healthy obese patients: an adaptive phenomenon?. Diabetes Care 2007; 30: 1494-1500
  • 12 Hillman JB, Dorn LD, Loucks TL, Berga SL. Obesity and the hypothalamic-pituitary-adrenal axis in adolescent girls. Metabolism 2012; 63: 341-348
  • 13 Fernandez-Real JM, Pugeat M, Grasa M, Broch M, Vendrell J, Brun J, Ricart W. Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: a population study. J Clin Endocrinol Metab 2002; 87: 4686-4690
  • 14 Weaver JU, Noonan K, Kopelman PG. An association between hypothalamic-pituitary dysfunction and peripheral endocrine function in extreme obesity. Clin Endocrinol (Oxf) 1991; 35: 97-102
  • 15 Katsuki A, Sumida Y, Murashima S, Fujii M, Ito K, Tsuchihashi K, Murata K, Yano Y, Shima T. Acute and chronic regulation of serum sex hormone-binding globulin levels by plasma insulin concentrations in male noninsulin-dependent diabetes mellitus patients. J Clin Endocrinol Metab 1996; 81: 2515-2519
  • 16 Crave JC, Fimbel S, Lejeune H, Cugnardey N, Dechaud H, Pugeat M. Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women. J Clin Endocrinol Metab 1995; 80: 2057-2062
  • 17 Steptoe A, Ussher M. Smoking, cortisol and nicotine. Int J Psychophysiol 2006; 59: 228-235
  • 18 Baron JA, Comi RJ, Cryns V, Brinck-Johnsen T, Mercer NG. The effect of cigarette smoking on adrenal cortical hormones. The Journal of pharmacology and experimental therapeutics 1995; 272: 151-155
  • 19 Calo WA, Ortiz AP, Suarez E, Guzman M, Perez CM.. Association of Cigarette Smoking and Metabolic Syndrome in a Puerto Rican Adult Population. J Immigr Minor Health 2012; June: 24 (Epub ahead of print)
  • 20 Wang T, Chen M, Liu L, Cheng H, Yan YE, Feng YH, Wang H. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production. Toxicol Appl Pharmacol 2011; 257: 328-337
  • 21 Morgan TM, Crawford L, Stoller A, Toth D, Yeo KT, Baron JA. Acute effects of nicotine on serum glucose insulin growth hormone and cortisol in healthy smokers. Metab Clin Exper 2004; 53: 578-582
  • 22 Meisinger C, Doring A, Thorand B, Lowel H. Association of cigarette smoking and tar and nicotine intake with development of type 2 diabetes mellitus in men and women from the general population: the MONICA/KORA Augsburg Cohort Study. Diabetologia 2006; 49: 1770-1776
  • 23 Keys A, Fidanza F, Karvonen MJ, Kimura N, Taylor HL. Indices of relative weight and obesity. J Chronic Dis 1972; 25: 329-343
  • 24 Kouri EM, Pope Jr HG, Katz DL, Oliva P. Fat-free mass index in users and nonusers of anabolic-androgenic steroids. Clin J Sport Med 1995; 5: 223-228
  • 25 Schutz Y, Kyle UU, Pichard C. Fat-free mass index and fat mass index percentiles in Caucasians aged 18–98 y. Int J Obes Relat Metab Disord 2002; 26: 953-960
  • 26 Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith Jr SC. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
  • 27 Piche ME, Weisnagel SJ, Corneau L, Nadeau A, Bergeron J, Lemieux S. The WHO and NCEP/ATPIII Definitions of the Metabolic Syndrome in Postmenopausal Women: Are They So Different?. Metab Syndr Relat Disord 2006; 4: 17-27
  • 28 Wu HY, Xu SY, Chen LL, Zhang HF. Waist to height ratio as a predictor of abdominal fat distribution in men. Chin J Physiol 2009; 52: 441-445
  • 29 Schneider HJ, Friedrich N, Klotsche J, Pieper L, Nauck M, John U, Dorr M, Felix S, Lehnert H, Pittrow D, Silber S, Volzke H, Stalla GK, Wallaschofski H, Wittchen HU. The predictive value of different measures of obesity for incident cardiovascular events and mortality. J Clin Endocrinol Metab 2010; 95: 1777-1785
  • 30 Stroud LR, Solomon C, Shenassa E, Papandonatos G, Niaura R, Lipsitt LP, Lewinn K, Buka SL. Long-term stability of maternal prenatal steroid hormones from the National Collaborative Perinatal Project: still valid after all these years. Psychoneuroendocrinology 2007; 32: 140-150
  • 31 Lewis JG, Lewis MG, Elder PA. An enzyme-linked immunosorbent assay for corticosteroid-binding globulin using monoclonal and polyclonal antibodies: decline in CBG following synthetic ACTH. Clin Chim Acta 2003; 328: 121-128
  • 32 Lewis JG, Manley L, Whitlow JC, Elder PA. Production of a monoclonal antibody to cortisol: application to a direct enzyme-linked immunosorbent assay of plasma. Steroids 1992; 57: 82-85
  • 33 Coolens JL, Van Baelen H, Heyns W. Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin. J Steroid Biochem 1987; 26: 197-202
  • 34 WHO . Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications 1999;
  • 35 Association AD. Executive Summary: Standards of Medical Care in Diabetes—2010. Current criteria for the diagnosis of diabetes 2010;
  • 36 Valsamakis G, Anwar A, Tomlinson JW, Shackleton CH, McTernan PG, Chetty R, Wood PJ, Banerjee AK, Holder G, Barnett AH, Stewart PM, Kumar S. 11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. J Clin Endocrinol Metab 2004; 89: 4755-4761
  • 37 Caldwell JD, Suleman F, Jirikowski GF. Internalization of sex hormone binding globulin into fibroblast 3T3 cells. Horm Metab Res 2007; 39: 620-622
  • 38 Bjorntorp P, Rosmond R. Obesity and cortisol. Nutrition 2000; 16: 924-936
  • 39 Baudrand R, Campino C, Carvajal CA, Olivieri O, Guidi G, Faccini G, Sateler J, Cornejo J, Martin BS, Dominguez JM, Cerda J, Mosso LM, Owen GI, Kalergis AM, Fardella CE. Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and beta cell dysfunction. Steroids 2011; 76: 1575-1581
  • 40 Klebanova EM, Balabolkin MI, Kreminskaia VM. The role of the fat tissue and its hormones in the mechanisms of insulin resistance and the development of type 2 diabetes mellitus. Klin Med (Mosk) 2007; 85: 20-27
  • 41 Hwang IC, Kim KK, Jee SH, Kang HC. A comparison of predictability of cardiovascular events between each metabolic component in patients with metabolic syndrome based on the revised National Cholesterol Education Program criteria. Yonsei Med J 2011; 52: 220-226
  • 42 Allen RP. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. Sleep Med 2001; 2: 359-361
  • 43 Unger RH. Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends Endocrinol Metab 2003; 14: 398-403
  • 44 Unger RH. Hyperleptinemia: protecting the heart from lipid overload. Hypertension 2005; 45: 1031-1034
  • 45 Hamdy O, Porramatikul S, Al-Ozairi E. Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev 2006; 2: 367-373
  • 46 Lewis JG, Shand BI, Elder PA, Scott RS. Plasma sex hormone-binding globulin rather than corticosteroid-binding globulin is a marker of insulin resistance in obese adult males. Diabetes Obes Metab 2004; 6: 259-263
  • 47 Badrick E, Kirschbaum C, Kumari M. The relationship between smoking status and cortisol secretion. J Clin Endocrinol Metab 2007; 92: 819-824
  • 48 Xu D, Liang G, Yan YE, He WW, Liu YS, Chen LB, Magdalou J, Wang H. Nicotine-induced over-exposure to maternal glucocorticoid and activated glucocorticoid metabolism causes hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic alterations in fetal rats. Toxicol Lett 2012; 209: 282-290
  • 49 Woods NF, Mitchell ES, Smith-Dijulio K.. Cortisol levels during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women’s Health Study. Menopause 2009; 16: 708-718