Redefining the Metabolic Syndrome: Contribution of Inflammatory and Sex Steroidal Antecedents
Main Article Content
Abstract
The MetS is a major health concern in the United States today being more prevalent in older individuals and in populations of specific racial/ethnic backgrounds. Although MetS is defined by a clustering of metabolic abnormalities including hyperglycemia, high blood pressure and central obesity, we propose the addition of pro-inflammatory adipokines (TNF-α, IL-6, Leptin, PAI-1) as well as CRP being incorporated into the physiological evaluation of those at risk for MetS. Much research exists to show that hyperinsulinemia and central obesity are integral to the development of MetS and that inflammatory adipokines and cytokines are increased in response to the development of insulin resistance and central obesity. However, questions remain as to whether or not these are the primary contributors or sole antecedents to the development of MetS. Androgenic steroids have also been proposed to contribute to the pathogenesis of MetS. More research is necessary to determine whether insulin resistance and central obesity mediate the relationship between androgens and MetS or whether androgenic sex steroids mediate the relationship between MetS and insulin resistance and/or central obesity or whether there is bidirectionality in aforementioned relationships.
Article Details
How to Cite
PERRY, Arlette; MARTIN, Lorena.
Redefining the Metabolic Syndrome: Contribution of Inflammatory and Sex Steroidal Antecedents.
Medical Research Archives, [S.l.], v. 2, n. 9, nov. 2015.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/382>. Date accessed: 26 dec. 2024.
Keywords
Inflammatory Markers, Metabolic Syndrome
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
Ervin, R. B. (2009). Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006. Natl Health Stat Report(13), 1-7.
Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., International Association for the Study of, Obesity. (2009). 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, 120(16), 1640-1645. doi: 10.1161/CIRCULATIONAHA.109.192644
Ford, E. S. (2005). Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care, 28(7), 1769-1778.
Grundy, S. M. (2008). Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol, 28(4), 629-636. doi: 10.1161/ATVBAHA.107.151092
Beilby J. Definition of metabolic syndrome: report of national heart lung, and blood institute American heart association conference on scientific issue related to definition. Circulation 2004;109:433-8
Regitz-Zagrosek, V., Lehmkuhl, E., & Weickert, M. O. (2006). Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol, 95(3), 136-147. doi: 10.1007/s00392-006-0351-5
Church, T. S. Physical Activity and Metabolic Syndrome Presented at the 51st Annual Meeting of the American College of Sports Medicine 2004
DeFronzo, R. A. (1997). Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis. Neth J Med, 50(5), 191-197.
Alberti, K. G., & Zimmet, P. Z. (1998). 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, 15(7), 539-553. doi: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S
Wisse, B. E. (2004). The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol, 15(11), 2792-2800. doi: 10.1097/01.ASN.0000141966.69934.21
Balistreri, C. R., Caruso, C., & Candore, G. (2010). The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediators Inflamm, 2010, 802078. doi: 10.1155/2010/802078
Grunfeld C, Feingold KR. (1991). The metabolic effects of tumor necrosis factor and other cytokines. Biotherapy(3), 143-158.
Kern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab, 280(5), E745-751.
Lau, D. C., Dhillon, B., Yan, H., Szmitko, P. E., & Verma, S. (2005). Adipokines: molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol, 288(5), H2031-2041. doi: 10.1152/ajpheart.01058.2004
Bray, G. A., Clearfield, M. B., Fintel, D. J., & Nelinson, D. S. (2009). Overweight and obesity: the pathogenesis of cardiometabolic risk. Clin Cornerstone, 9(4), 30-40; discussion 41-32.
Ho, S. S., Dhaliwal, S. S., Hills, A. P., & Pal, S. (2013). Effects of chronic exercise training on inflammatory markers in Australian overweight and obese individuals in a randomized controlled trial. Inflammation, 36(3), 625-632. doi: 10.1007/s10753-012-9584-9
Coelho, M., Oliveira, T., & Fernandes, R. (2013). Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci, 9(2), 191-200. doi: 10.5114/aoms.2013.33181
Carey, A. L., & Febbraio, M. A. (2004). Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia, 47(7), 1135-1142. doi: 10.1007/s00125-004-1447-y
Fantuzzi, G. Systemic effects of Inflammation: Adipose, Nutrition, and Interventions. Presented at the 61st Annual Meeting of the American College of Sports Medicine 2014
Erusan RR, Nalini D, Manohar G, Malathi R. Correlation between obesity and inflammation in cardiovascular disease- evaluation of leptin and inflammatory cytokines. Open J Endocr Met Dis 2012;2:7-15
Ridker, P. M. (2001). High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation, 103(13), 1813-1818.
LaMont, M. C-Reactive protein: Biology, Atherosclerosis as a Risk Factor and Physical Activity. Presented at the 51st Annual Meeting of the American College of Sports Medicine. June, 2004
Torres JL, Ridker PM. Clinical use of high sensitivity C-reactive protein for the prediction of adverse cardiovascular events. Curr Opin Cardiol. 2003; 18:471-78
Wee, C. C., Mukamal, K. J., Huang, A., Davis, R. B., McCarthy, E. P., & Mittleman, M. A. (2008). Obesity and C-reactive protein levels among white, black, and hispanic US adults. Obesity (Silver Spring), 16(4), 875-880. doi: 10.1038/oby.2008.7
Tomaszewski, M., Charchar, F. J., Przybycin, M., Crawford, L., Wallace, A. M., Gosek, K., . . . Dominiczak, A. F. (2003). Strikingly low circulating CRP concentrations in ultramarathon runners independent of markers of adiposity: how low can you go? Arterioscler Thromb Vasc Biol, 23(9), 1640-1644. doi: 10.1161/01.ATV.0000087036.75849.0B
Ahima, R. S. (2006). Adipose tissue as an endocrine organ. Obesity (Silver Spring), 14 Suppl 5, 242S-249S. doi: 10.1038/oby.2006.317
Bruun, J. M., Lihn, A. S., Verdich, C., Pedersen, S. B., Toubro, S., Astrup, A., & Richelsen, B. (2003). Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab, 285(3), E527-533. doi: 10.1152/ajpendo.00110.2003
Leshan, R. L., Bjornholm, M., Munzberg, H., & Myers, M. G., Jr. (2006). Leptin receptor signaling and action in the central nervous system. Obesity (Silver Spring), 14 Suppl 5, 208S-212S. doi: 10.1038/oby.2006.310
Chen, K., Li, F., Li, J., Cai, H., Strom, S., Bisello, A., . . . Zhao, A. Z. (2006). Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med, 12(4), 425-432. doi: 10.1038/nm1372
Chung, C. P., Long, A. G., Solus, J. F., Rho, Y. H., Oeser, A., Raggi, P., & Stein, C. M. (2009). Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis. Lupus, 18(9), 799-806. doi: 10.1177/0961203309103582
Wallace, A. M., McMahon, A. D., Packard, C. J., Kelly, A., Shepherd, J., Gaw, A., & Sattar, N. (2001). Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation, 104(25), 3052-3056.
Samad, F., Uysal, K. T., Wiesbrock, S. M., Pandey, M., Hotamisligil, G. S., & Loskutoff, D. J. (1999). Tumor necrosis factor alpha is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1. Proc Natl Acad Sci U S A, 96(12), 6902-6907.
Gallistl, S., Sudi, K. M., Borkenstein, M., Troebinger, M., Weinhandl, G., & Muntean, W. (2000). Determinants of haemostatic risk factors for coronary heart disease in obese children and adolescents. Int J Obes Relat Metab Disord, 24(11), 1459-1464.
Haffner, S. M. (2003). Insulin resistance, inflammation, and the prediabetic state. Am J Cardiol, 92(4A), 18J-26J.
Alessi, M. C., & Juhan-Vague, I. (2006). PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler Thromb Vasc Biol, 26(10), 2200-2207. doi: 10.1161/01.ATV.0000242905.41404.68
Gonzalez, M., del Mar Bibiloni, M., Pons, A., Llompart, I., & Tur, J. A. (2012). Inflammatory markers and metabolic syndrome among adolescents. Eur J Clin Nutr, 66(10), 1141-1145. doi: 10.1038/ejcn.2012.112
Festa, A., D'Agostino, R., Jr., Mykkanen, L., Tracy, R. P., Zaccaro, D. J., Hales, C. N., & Haffner, S. M. (1999). Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. The Insulin Resistance Atherosclerosis Study (IRAS). Arterioscler Thromb Vasc Biol, 19(3), 562-568.
Haffner, S. M. (2003). Insulin resistance, inflammation, and the prediabetic state. Am J Cardiol, 92(4A), 18J-26J.
Stern, M. P. (1995). Diabetes and cardiovascular disease. The "common soil" hypothesis. Diabetes, 44(4), 369-374.
Karastergiou, K., Smith, S. R., Greenberg, A. S., & Fried, S. K. (2012). Sex differences in human adipose tissues - the biology of pear shape. Biol Sex Differ, 3(1), 13. doi: 10.1186/2042-6410-3-13
Gannon, J. G. Regulation of Inflammation in Skeletal Muscle Presented at the 61st Annual Meeting of the American College of Sports Medicine 2014
Brand, J. S., van der Tweel, I., Grobbee, D. E., Emmelot-Vonk, M. H., & van der Schouw, Y. T. (2011). Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. Int J Epidemiol, 40(1), 189-207. doi: 10.1093/ije/dyq158
Kapoor, D., Goodwin, E., Channer, K. S., & Jones, T. H. (2006). Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol, 154(6), 899-906. doi: 10.1530/eje.1.02166
Khaw KT, Berrett-Connor E 1992 Lower endogenous androgens predict central adiposity in men. Ann Epidemiol 2:675-682
Laaksonen, D. E., Niskanen, L., Punnonen, K., Nyyssonen, K., Tuomainen, T. P., Valkonen, V. P., . . . Salonen, J. T. (2004). Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care, 27(5), 1036-1041.
Stellato, R. K., Feldman, H. A., Hamdy, O., Horton, E. S., & McKinlay, J. B. (2000). Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care, 23(4), 490-494.
Heufelder, A. E., Saad, F., Bunck, M. C., & Gooren, L. (2009). Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl, 30(6), 726-733. doi: 10.2164/jandrol.108.007005
Kupelian, V., Hayes, F. J., Link, C. L., Rosen, R., & McKinlay, J. B. (2008). Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab, 93(9), 3403-3410. doi: 10.1210/jc.2008-0054
Rees, D. A., & Dayan, C. M. (2011). Commentary: testosterone and the metabolic syndrome: cause or consequence? Int J Epidemiol, 40(1), 207-209. doi: 10.1093/ije/dyq254
Niskanen, L., Laaksonen, D. E., Punnonen, K., Mustajoki, P., Kaukua, J., & Rissanen, A. (2004). Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab, 6(3), 208-215. doi: 10.1111/j.1462-8902.2004.00335.x
Goodpaster, B. H., Kelley, D. E., Wing, R. R., Meier, A., & Thaete, F. L. (1999). Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes, 48(4), 839-847.
Mohr, B. A., Bhasin, S., Link, C. L., O'Donnell, A. B., & McKinlay, J. B. (2006). The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Eur J Endocrinol, 155(3), 443-452. doi: 10.1530/eje.1.02241
Plymate, S. R., Matej, L. A., Jones, R. E., & Friedl, K. E. (1988). Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab, 67(3), 460-464. doi: 10.1210/jcem-67-3-460
Pitteloud, N., Mootha, V. K., Dwyer, A. A., Hardin, M., Lee, H., Eriksson, K. F., . . . Hayes, F. J. (2005). Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care, 28(7), 1636-1642.
Torrens, J. I., Sutton-Tyrrell, K., Zhao, X., Matthews, K., Brockwell, S., Sowers, M., & Santoro, N. (2009). Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in midlife women: study of Women's Health Across the Nation. Menopause, 16(2), 257-264. doi: 10.1097/gme.0b013e318185e249
Perry, A., Wang, X., Goldberg, R., Ross, R., & Jackson, L. (2013). Androgenic sex steroids contribute to metabolic risk beyond intra-abdominal fat in overweight/obese black and white women. Obesity (Silver Spring), 21(8), 1618-1624. doi: 10.1002/oby.20204
Pasquali, R., & Gambineri, A. (2006). Insulin-sensitizing agents in women with polycystic ovary syndrome. Fertil Steril, 86 Suppl 1, S28-29. doi: 10.1016/j.fertnstert.2006.04.012
Crave, J. C., Fimbel, S., Lejeune, H., Cugnardey, N., Dechaud, H., & Pugeat, M. (1995). Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women. J Clin Endocrinol Metab, 80(7), 2057-2062. doi: 10.1210/jcem.80.7.7608255
Barbieri, R. L., Makris, A., Randall, R. W., Daniels, G., Kistner, R. W., & Ryan, K. J. (1986). Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab, 62(5), 904-910. doi: 10.1210/jcem-62-5-904
Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., International Association for the Study of, Obesity. (2009). 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, 120(16), 1640-1645. doi: 10.1161/CIRCULATIONAHA.109.192644
Ford, E. S. (2005). Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care, 28(7), 1769-1778.
Grundy, S. M. (2008). Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol, 28(4), 629-636. doi: 10.1161/ATVBAHA.107.151092
Beilby J. Definition of metabolic syndrome: report of national heart lung, and blood institute American heart association conference on scientific issue related to definition. Circulation 2004;109:433-8
Regitz-Zagrosek, V., Lehmkuhl, E., & Weickert, M. O. (2006). Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol, 95(3), 136-147. doi: 10.1007/s00392-006-0351-5
Church, T. S. Physical Activity and Metabolic Syndrome Presented at the 51st Annual Meeting of the American College of Sports Medicine 2004
DeFronzo, R. A. (1997). Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis. Neth J Med, 50(5), 191-197.
Alberti, K. G., & Zimmet, P. Z. (1998). 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, 15(7), 539-553. doi: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S
Wisse, B. E. (2004). The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol, 15(11), 2792-2800. doi: 10.1097/01.ASN.0000141966.69934.21
Balistreri, C. R., Caruso, C., & Candore, G. (2010). The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediators Inflamm, 2010, 802078. doi: 10.1155/2010/802078
Grunfeld C, Feingold KR. (1991). The metabolic effects of tumor necrosis factor and other cytokines. Biotherapy(3), 143-158.
Kern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab, 280(5), E745-751.
Lau, D. C., Dhillon, B., Yan, H., Szmitko, P. E., & Verma, S. (2005). Adipokines: molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol, 288(5), H2031-2041. doi: 10.1152/ajpheart.01058.2004
Bray, G. A., Clearfield, M. B., Fintel, D. J., & Nelinson, D. S. (2009). Overweight and obesity: the pathogenesis of cardiometabolic risk. Clin Cornerstone, 9(4), 30-40; discussion 41-32.
Ho, S. S., Dhaliwal, S. S., Hills, A. P., & Pal, S. (2013). Effects of chronic exercise training on inflammatory markers in Australian overweight and obese individuals in a randomized controlled trial. Inflammation, 36(3), 625-632. doi: 10.1007/s10753-012-9584-9
Coelho, M., Oliveira, T., & Fernandes, R. (2013). Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci, 9(2), 191-200. doi: 10.5114/aoms.2013.33181
Carey, A. L., & Febbraio, M. A. (2004). Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia, 47(7), 1135-1142. doi: 10.1007/s00125-004-1447-y
Fantuzzi, G. Systemic effects of Inflammation: Adipose, Nutrition, and Interventions. Presented at the 61st Annual Meeting of the American College of Sports Medicine 2014
Erusan RR, Nalini D, Manohar G, Malathi R. Correlation between obesity and inflammation in cardiovascular disease- evaluation of leptin and inflammatory cytokines. Open J Endocr Met Dis 2012;2:7-15
Ridker, P. M. (2001). High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation, 103(13), 1813-1818.
LaMont, M. C-Reactive protein: Biology, Atherosclerosis as a Risk Factor and Physical Activity. Presented at the 51st Annual Meeting of the American College of Sports Medicine. June, 2004
Torres JL, Ridker PM. Clinical use of high sensitivity C-reactive protein for the prediction of adverse cardiovascular events. Curr Opin Cardiol. 2003; 18:471-78
Wee, C. C., Mukamal, K. J., Huang, A., Davis, R. B., McCarthy, E. P., & Mittleman, M. A. (2008). Obesity and C-reactive protein levels among white, black, and hispanic US adults. Obesity (Silver Spring), 16(4), 875-880. doi: 10.1038/oby.2008.7
Tomaszewski, M., Charchar, F. J., Przybycin, M., Crawford, L., Wallace, A. M., Gosek, K., . . . Dominiczak, A. F. (2003). Strikingly low circulating CRP concentrations in ultramarathon runners independent of markers of adiposity: how low can you go? Arterioscler Thromb Vasc Biol, 23(9), 1640-1644. doi: 10.1161/01.ATV.0000087036.75849.0B
Ahima, R. S. (2006). Adipose tissue as an endocrine organ. Obesity (Silver Spring), 14 Suppl 5, 242S-249S. doi: 10.1038/oby.2006.317
Bruun, J. M., Lihn, A. S., Verdich, C., Pedersen, S. B., Toubro, S., Astrup, A., & Richelsen, B. (2003). Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab, 285(3), E527-533. doi: 10.1152/ajpendo.00110.2003
Leshan, R. L., Bjornholm, M., Munzberg, H., & Myers, M. G., Jr. (2006). Leptin receptor signaling and action in the central nervous system. Obesity (Silver Spring), 14 Suppl 5, 208S-212S. doi: 10.1038/oby.2006.310
Chen, K., Li, F., Li, J., Cai, H., Strom, S., Bisello, A., . . . Zhao, A. Z. (2006). Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med, 12(4), 425-432. doi: 10.1038/nm1372
Chung, C. P., Long, A. G., Solus, J. F., Rho, Y. H., Oeser, A., Raggi, P., & Stein, C. M. (2009). Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis. Lupus, 18(9), 799-806. doi: 10.1177/0961203309103582
Wallace, A. M., McMahon, A. D., Packard, C. J., Kelly, A., Shepherd, J., Gaw, A., & Sattar, N. (2001). Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation, 104(25), 3052-3056.
Samad, F., Uysal, K. T., Wiesbrock, S. M., Pandey, M., Hotamisligil, G. S., & Loskutoff, D. J. (1999). Tumor necrosis factor alpha is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1. Proc Natl Acad Sci U S A, 96(12), 6902-6907.
Gallistl, S., Sudi, K. M., Borkenstein, M., Troebinger, M., Weinhandl, G., & Muntean, W. (2000). Determinants of haemostatic risk factors for coronary heart disease in obese children and adolescents. Int J Obes Relat Metab Disord, 24(11), 1459-1464.
Haffner, S. M. (2003). Insulin resistance, inflammation, and the prediabetic state. Am J Cardiol, 92(4A), 18J-26J.
Alessi, M. C., & Juhan-Vague, I. (2006). PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler Thromb Vasc Biol, 26(10), 2200-2207. doi: 10.1161/01.ATV.0000242905.41404.68
Gonzalez, M., del Mar Bibiloni, M., Pons, A., Llompart, I., & Tur, J. A. (2012). Inflammatory markers and metabolic syndrome among adolescents. Eur J Clin Nutr, 66(10), 1141-1145. doi: 10.1038/ejcn.2012.112
Festa, A., D'Agostino, R., Jr., Mykkanen, L., Tracy, R. P., Zaccaro, D. J., Hales, C. N., & Haffner, S. M. (1999). Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. The Insulin Resistance Atherosclerosis Study (IRAS). Arterioscler Thromb Vasc Biol, 19(3), 562-568.
Haffner, S. M. (2003). Insulin resistance, inflammation, and the prediabetic state. Am J Cardiol, 92(4A), 18J-26J.
Stern, M. P. (1995). Diabetes and cardiovascular disease. The "common soil" hypothesis. Diabetes, 44(4), 369-374.
Karastergiou, K., Smith, S. R., Greenberg, A. S., & Fried, S. K. (2012). Sex differences in human adipose tissues - the biology of pear shape. Biol Sex Differ, 3(1), 13. doi: 10.1186/2042-6410-3-13
Gannon, J. G. Regulation of Inflammation in Skeletal Muscle Presented at the 61st Annual Meeting of the American College of Sports Medicine 2014
Brand, J. S., van der Tweel, I., Grobbee, D. E., Emmelot-Vonk, M. H., & van der Schouw, Y. T. (2011). Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. Int J Epidemiol, 40(1), 189-207. doi: 10.1093/ije/dyq158
Kapoor, D., Goodwin, E., Channer, K. S., & Jones, T. H. (2006). Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol, 154(6), 899-906. doi: 10.1530/eje.1.02166
Khaw KT, Berrett-Connor E 1992 Lower endogenous androgens predict central adiposity in men. Ann Epidemiol 2:675-682
Laaksonen, D. E., Niskanen, L., Punnonen, K., Nyyssonen, K., Tuomainen, T. P., Valkonen, V. P., . . . Salonen, J. T. (2004). Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care, 27(5), 1036-1041.
Stellato, R. K., Feldman, H. A., Hamdy, O., Horton, E. S., & McKinlay, J. B. (2000). Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care, 23(4), 490-494.
Heufelder, A. E., Saad, F., Bunck, M. C., & Gooren, L. (2009). Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl, 30(6), 726-733. doi: 10.2164/jandrol.108.007005
Kupelian, V., Hayes, F. J., Link, C. L., Rosen, R., & McKinlay, J. B. (2008). Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab, 93(9), 3403-3410. doi: 10.1210/jc.2008-0054
Rees, D. A., & Dayan, C. M. (2011). Commentary: testosterone and the metabolic syndrome: cause or consequence? Int J Epidemiol, 40(1), 207-209. doi: 10.1093/ije/dyq254
Niskanen, L., Laaksonen, D. E., Punnonen, K., Mustajoki, P., Kaukua, J., & Rissanen, A. (2004). Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab, 6(3), 208-215. doi: 10.1111/j.1462-8902.2004.00335.x
Goodpaster, B. H., Kelley, D. E., Wing, R. R., Meier, A., & Thaete, F. L. (1999). Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes, 48(4), 839-847.
Mohr, B. A., Bhasin, S., Link, C. L., O'Donnell, A. B., & McKinlay, J. B. (2006). The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Eur J Endocrinol, 155(3), 443-452. doi: 10.1530/eje.1.02241
Plymate, S. R., Matej, L. A., Jones, R. E., & Friedl, K. E. (1988). Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab, 67(3), 460-464. doi: 10.1210/jcem-67-3-460
Pitteloud, N., Mootha, V. K., Dwyer, A. A., Hardin, M., Lee, H., Eriksson, K. F., . . . Hayes, F. J. (2005). Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care, 28(7), 1636-1642.
Torrens, J. I., Sutton-Tyrrell, K., Zhao, X., Matthews, K., Brockwell, S., Sowers, M., & Santoro, N. (2009). Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in midlife women: study of Women's Health Across the Nation. Menopause, 16(2), 257-264. doi: 10.1097/gme.0b013e318185e249
Perry, A., Wang, X., Goldberg, R., Ross, R., & Jackson, L. (2013). Androgenic sex steroids contribute to metabolic risk beyond intra-abdominal fat in overweight/obese black and white women. Obesity (Silver Spring), 21(8), 1618-1624. doi: 10.1002/oby.20204
Pasquali, R., & Gambineri, A. (2006). Insulin-sensitizing agents in women with polycystic ovary syndrome. Fertil Steril, 86 Suppl 1, S28-29. doi: 10.1016/j.fertnstert.2006.04.012
Crave, J. C., Fimbel, S., Lejeune, H., Cugnardey, N., Dechaud, H., & Pugeat, M. (1995). Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women. J Clin Endocrinol Metab, 80(7), 2057-2062. doi: 10.1210/jcem.80.7.7608255
Barbieri, R. L., Makris, A., Randall, R. W., Daniels, G., Kistner, R. W., & Ryan, K. J. (1986). Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab, 62(5), 904-910. doi: 10.1210/jcem-62-5-904