Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

The central roles of obesity-associated dyslipidaemia, endothelial activation and cytokines in the Metabolic Syndrome—an analysis by structural equation modelling

International Journal of Obesity volume 26, pages 994–1008 (2002)Cite this article

Abstract

Hypothesis: The multi-faceted components of the metabolic syndrome now include markers of inflammation and endothelial activation. Despite this growing body of epidemiological data, standard statistical methods fail to evaluate the nature of these associations adequately. In this pilot study, we hypothesize that obesity may lead to endothelial activation which is in part mediated by dyslipidaemia and proinflammatory cytokines. These factors interact to give rise to hyperinsulinaemia, hypertension and an anti-fibrinolytic state. To test this hypothesis, we used confirmatory factor analysis and structural equation modelling to fit these data to a model designed on theoretical grounds.

Methods: Metabolic syndrome variables, cytokines (IL6 and TNFα), markers of inflammation and endothelial activation were measured in 107 Caucasian non-diabetic subjects aged 40–75 y. Using confirmatory factor analysis, we identified six factors to represent composite measurements of blood pressure, obesity, dyslipidaemia, hyperinsulinaemia, endothelial activation and the anti-fibrinolytic state. We fitted these variables to two separate models, one using IL-6 and the other TNFα as the cytokine, and examined the inter-relationships (path analysis) amongst these variables, based on the above hypothesis.

Results: Men were centrally more obese and had increased markers of endothelial activation, inflammation and the anti-fibrinolytic state as well as hyperinsulinaemia and dyslipidaemia, compared with women. Obesity indexes (both body mass index and waist–hip ratio) were strongly associated with multiple cardiovascular risk factors. Both IL6 and TNFα were correlated with age, male gender, obesity indexes and markers of endothelial activation. Only IL-6 was associated with smoking while TNFα was correlated with hyperinsulinaemia. In the TNFα model, 61% of the obesity variance was explained by male gender, 36% of TNFα variance by age and dyslipidaemia, 43% of dyslipidaemia variance by age and obesity, 33% of hyperinsulinaemia variance by dyslipidaemia and a non-smoking state, 29% of anti-fibrinolytic state variance by hyperinsulinaemia, 65% of endothelial activation variance by TNFα, dyslipidaemia and hyperinsulinaemia, 34% of blood pressure variance by hyperinsulinaemia and endothelial activation. In the IL-6 model, we observed similar relationships except that 23% of IL6 variance was explained by smoking and age.

Conclusions: Using confirmatory factor analysis and structural equation modelling, we found that obesity, dyslipidemia and cytokines were the principal explanatory variables for the various components of the metabolic syndrome, with IL6 and TNFα having different explanatory variables and effects. These complex inter-relationships were in part mediated by hyperinsulinaemia and endothelial activation. While this hypothetical model was based on scientific evidence, supported by rigorous analysis, it requires further confirmation in large-scale prospective studies. Given the complexity of the biological system and its interactions with exogenous factors, structural equation modelling provides a useful scientific tool for hypothesis testing, complementary to the more traditional experimental and cohort studies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Reaven GM . Role of insulin resistance in human disease. Banting lecture 1988 Diabetes 1988 37: 1595–1607.

    Article  CAS  PubMed  Google Scholar 

  2. Modan M, Halkin H, Almog S, Lusky A, Shefi M . Hyperinsulinemia. A link between hypertension, obesity and glucose intolerance J Clin Invest 1985 75: 809–817.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S . Insulin resistance in essential hypertension New Engl J Med 1987 317: 350–357.

    CAS  PubMed  Google Scholar 

  4. Kaplan NM . The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension Arch Intern Med 1989 149: 1514–1520.

    CAS  PubMed  Google Scholar 

  5. Bjórntorp P . Metabolic implications of body fat distribution Diabetes Care 1991 14: 1132–1143.

    PubMed  Google Scholar 

  6. Frayn KN, Coppack SW . Insulin resistance, adipose tissue and coronary heart disease Clin Sci 1992 82: 1–8.

    CAS  Google Scholar 

  7. Boyko EJ, Leonetti DL, Bergstrom RW, Newell-Morris L, Fuji WY . Visceral adipostiy, fasting plasma insulin, and blood pressure in Japanese-Americans Diabetes Care 1995 18: 174–181.

    CAS  PubMed  Google Scholar 

  8. Jaap AJ, Shore AC, Tooke JE . Relationship of insulin resistance to microvascular dysfunction in subjects with fasting hyperglycemia Diabetologia 1997 40: 238–243.

    CAS  PubMed  Google Scholar 

  9. Enderle M-D, Benda N, Schmuelling R-M, Haering H, Pfohl M . Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects Diabetes Care 1998 21: 271–277.

    CAS  PubMed  Google Scholar 

  10. Knock GA, McCarthy AL, Lowy C, Poston L . Association of gestational diabetes with abnormal maternal vascular endothelial function Br J Obstet Gynaecol 1997 104: 229–234.

    CAS  PubMed  Google Scholar 

  11. Leeson CP, Whincup PH, Cook DG, Donald AE, Papacosta O, Lucas A, Deanfield JE . Flow mediated dilatation in 9 to 11 year old children: the influence of intrauterine and childhood factors Circulation 1997 96: 2233–2238.

    CAS  PubMed  Google Scholar 

  12. Goodfellow J, Bellamy MF, Gorman ST, Brownlee M, Ramsey MW, Lewis MJ, Davies DP, Henderson AH . Endothelial function is impaired in fit young adults of low birth weight Cardiovasc Res 1998 40: 600–606.

    CAS  PubMed  Google Scholar 

  13. Tan ES, Emmanuel SC, Chew SK, Tan BY, Tan CE . Isolated low HDL cholesterol: an insulin resistant state only in the presence of fasting hypertriglyceridemia Diabetes 1999 48: 1088–1092.

    PubMed  Google Scholar 

  14. Vakkilainen J, Makimattila S, Seppala-Lindroos A, Vehkavaara S, Lahdenpera S, Groop PH, Taskinen MR, Yki-Järvinen H . Endothelial dysfunction in men with small dense LDL particles Circulation 2000 102: 716–721.

    CAS  PubMed  Google Scholar 

  15. Tan KC, Ali VH, Chow WS, Chau MT, Leong L, Lam KS . Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes J Clin Endocrinol Metab 1999 84: 3212–3216.

    CAS  PubMed  Google Scholar 

  16. Taskinen M-R . Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus Diabetes 1992 41 (Suppl 2): 12–17.

    PubMed  Google Scholar 

  17. Juhan-Vague I, Alessi MC, Vague P . Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes melltius Ann Med 1996 28: 371–380.

    CAS  PubMed  Google Scholar 

  18. Juhan-Vague I, Pyke S, Alessi MC, Jespersen J, Haverkate F, Thompson SG . Myocardial ischemia/coronary artery vasoconstriction/thrombosis/myocardial infarction: fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris Circulation 1996 94: 2057–2063.

    CAS  PubMed  Google Scholar 

  19. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM . C-reactive protein, interleukin 6 and risk of developing type 2 diabetes mellitus JAMA 2001 286: 327–334.

    CAS  PubMed  Google Scholar 

  20. Schmidt MI, Duncan BB, Sharrett AR, Lindberg G, Savage PJ, Offenbacher S, Azanbuja MI, Tracy RP, Heiss C for the ARIC investigators. Markers of inflammation and prediction of diabetes mellitus in adults (atherosclerosis risks in communities study): a cohort study Lancet 1999 353: 1649–1652.

    CAS  PubMed  Google Scholar 

  21. Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC . Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilites Angina Pectoris Study Group New Engl J Med 1995 332: 635–641.

    CAS  PubMed  Google Scholar 

  22. Ridker PM, Cushman M, Stampfer MJ, Tracey RP, Hennekens CH . Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men New Engl J Med 1997 336: 973–979.

    CAS  PubMed  Google Scholar 

  23. Jöreskog KG, Sörbom D . LISREL 8 user's reference guide Scientific Software: Chicago, IL 1993.

    Google Scholar 

  24. Jöreskog KG . Testing structural equation models In: Bollen KA, Long JS (eds) Testing structural equation models Sage: Newbury Park, CA 1993 294–316.

    Google Scholar 

  25. Chan JCN, Cheung JCK, Lau EMC, Woo J, Swaminathan R, Cockram CS . The Metabolic Syndrome in Hong Kong Chinese—the inter-relationships amongst its components analysed by structural equation modeling Diabetes Care 1996 19: 953–959.

    CAS  PubMed  Google Scholar 

  26. DeFronzo RA . Pathogenesis of Type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Rev 1997 5: 177–269.

    Google Scholar 

  27. Facchini F, Chen YD, Clinkingbeard C, Jeppesen J, Reaven GM . Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension Am J Hypertens 1992 5: 694–699.

    CAS  PubMed  Google Scholar 

  28. Williams B . Insulin resistance: the shape of things to come Lancet 1994 344: 521–524.

    CAS  PubMed  Google Scholar 

  29. Saad MF, Lillioja S, Nyomba BL, Castillo C, Ferraro R, De Gregorio M, Ravussin E, Knowler WC, Bennett PH, Howard RV, Bogardus C . Racial differences in the relation between blood pressure and insulin resistance New Engl J Med 1991 324: 733–739.

    CAS  PubMed  Google Scholar 

  30. Baron AD . Hemodynamic actions of insulin Am J Physiol 1994 267 (2 pt 1): E187–E202.

    CAS  PubMed  Google Scholar 

  31. Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L . Effect of insulin and glucose infusion on sympathatic nervous system activity in normal man Diabetes 1981 30: 219–225.

    CAS  PubMed  Google Scholar 

  32. Sawicki PT, Heinemann L, Starke A, Berger M . Hyperinsulinaemia is not linked with blood pressure elevation in patients with insulinoma Diabetologia 1992 35: 649–652.

    CAS  PubMed  Google Scholar 

  33. Peiris AN, Stagner JI, Vogel RL, Nakagawa A, Samols E . Body fat distribution and peripheral insulin sensitivity in healthy men: Role of insulin pulsatility J Clin Endocinol Metab 1992 75: 290–293.

    CAS  Google Scholar 

  34. Fontbonne A, Thibult M, Eschwege E, Ducimetiere P . Body fat distribution and coronary heart disease mortality in subjects with impaired glucose tolerance and diabetes mellitus: the Paris Prospective Study, a 15 year follow-up Diabetologia 1992 35: 464–468.

    CAS  PubMed  Google Scholar 

  35. Bujalska IJ, Kumar S, Stewart PM . Does central obesity reflect ‘Cushing's disease of the omentum’? Lancet 1997 349: 1210–1213.

    CAS  PubMed  Google Scholar 

  36. Lee ZSK, Chan JCN, Yeung VTF, Chow CC, Lau MSW, Ko GTC, Li JKY, Cockram CS, Critchley JAJH . Plasma insulin, growth hormone, cortisol and central obesity among young Chinese Type 2 diabetic patients Diabetes Care 1999 22: 1450–1457.

    CAS  PubMed  Google Scholar 

  37. Bergman RN . New concepts in extracellular signalling for insulin action: the single gateway hypothesis Rec Prog Hormone Res 1997 52: 359–385.

    CAS  Google Scholar 

  38. Randle PJ, Hales CN, Garland PB, Newsholme EA . The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus Lancet 1963 ii: 785–789.

    Google Scholar 

  39. Mohamed-Ali V, Gould MM, Gillies S, Goubet S, Yudkin JS, Haines AP . Association of proinsulin-like molecules with lipids and fibrinogen in non-diabetic subjects—evidence against a modulating role for insulin Diabetologia 1995 38: 1110–1116.

    CAS  PubMed  Google Scholar 

  40. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V on behalf of the University College London Interleukin-6 Group. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Athersclerosis 2000 209: 209–214.

    Google Scholar 

  41. Vallance P, Collier J, Bhagat K . Infection, inflammation and infarction: does acute endothelial dysfunction provide a link? Lancet 1997 349: 1391–1392.

    CAS  PubMed  Google Scholar 

  42. Maseri A, Biasucci LM, Liuzzo G . Inflammation in ischaemic heart disease Br Med J 1996 312: 1049–1050.

    CAS  Google Scholar 

  43. Ridker PM, Hennekens CH, Buring JE, Kundsin R, Shih J . Baseline IgG antibody titers to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus and the risk for cardiovascular disease in women Ann Intern Med 2000 131: 573–577.

    Google Scholar 

  44. Tracy RP, Psaty BM, Macy E, Bovill EG, Cushman M, Cornell ES, Kuller LH . Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects Arterioscler Thromb Vasc Biol 1997 17: 2167–2176.

    CAS  PubMed  Google Scholar 

  45. Björntorp P . Fatty acids, hyperinsulinemia, and insulin resistance: which comes first? Curr Opin Lipidol 1994 5: 166–174.

    PubMed  Google Scholar 

  46. Libby P, Ridker PM . Novel inflammatory markers of coronary risk: theory versus practice Circulation 1999 100: 1148–1150.

    CAS  PubMed  Google Scholar 

  47. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM . Increased adipose tissue expression of tumour necrosis factor α in human obesity and insulin resistance J Clin Invest 1995 95: 2409–2415.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Yudkin JS, Stehouwer CDA, Emeis JJ, Coppack SW . C-reactive protein in healthy subjects: association with obesity, insulin resistance, and endothelial dysfunction Arterioscler Thromb Vasc Biol 1999 19: 972–978.

    CAS  PubMed  Google Scholar 

  49. Foyle W-J, Carstensen E, Fernandez M, Yudkin JS . A longitudinal study of associations of microalbuminuria with the insulin resistance syndrome and sodium–lithium countertransport in non-diabetic subjects Arterioscler Thromb Vasc Biol 1995 15: 1330–1337.

    CAS  PubMed  Google Scholar 

  50. DeFronzo RA, Ferrannini E . Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease Diabetes Care 1991 14: 173–194.

    CAS  PubMed  Google Scholar 

  51. Frohlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, Muche R, Brenner H, Koenig W . Association between C-reactive protein and features of the Metabolic Syndrome Diabetes Care 2000 23: 1835–1839.

    CAS  PubMed  Google Scholar 

  52. Hotamisligil GS, Spiegelman BM . Tumor necrosis factor α: a key component of the obesity-diabetes link Diabetes 1994 43: 1271–1278.

    CAS  PubMed  Google Scholar 

  53. Pickup JC, Mattock MB, Chusney GD, Burt D . NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X Diabetologia 1997 40: 1286–1292.

    CAS  PubMed  Google Scholar 

  54. Van Snick J . Interleukin-6: An overview A Rev Immunol 1990 8: 253–278.

    CAS  Google Scholar 

  55. Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Björntorp P, Tibblin G . Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 y follow up of participants in the study of men born in 1913 Br Med J 1984 288: 1401–1404.

    CAS  Google Scholar 

  56. Juhan-Vague I, Alessi MC . PAI-I, obesity, insulin resistance and risk of cardiovascular events Thromb Haemost 1997 78: 656–660.

    CAS  PubMed  Google Scholar 

  57. Valmadrid CT, Klein R, Moss SE, Klein BEK . The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus Ann Intern Med 2000 160: 1093–1100.

    CAS  Google Scholar 

  58. Imperatore G, Riccardi G, Lovine C, Rivellese AA, Vaccaro O . Plasma fibrinogen: a new factor of the metabolic syndrome population-based study Diabetes Care 1998 21: 649–654.

    CAS  PubMed  Google Scholar 

  59. Tchernof A, Labrie F, Belanger A, Prud'homme D, Bouchard C, Tremblay A, Nadeau A, Despres JP . Relationship between endogenous steroid hormone, sex hormone binding globulin and lipoprotein levels in men: contribution of visceral obesity, insulin levels and other metabolic variables Athersclerosis 1997 133: 235–244.

    CAS  Google Scholar 

  60. Marin P, Holmang S, Jonsson L, Sjostrom L, Kvist H, Holm G, Lindstedt G, Bjorntorp P . The effects of testosterone treatment on body composition and metabolism in middle-age obese men Int J Obes Relat Metab Disord 1992 16: 991–997.

    CAS  PubMed  Google Scholar 

  61. Kelley DE, Mandarino LJ . Fuel selection in human skeletal muscle in insulin resistance: a reexamination Diabetes 2000 49: 677–683.

    CAS  PubMed  Google Scholar 

  62. Goodpaster BH, Kelley DE . Role of muscle in triglyceride metabolism Curr Opin Lipidol 1998 9: 231–236.

    CAS  PubMed  Google Scholar 

  63. Austin MA, Hokanson JE, Edwards KL . Hypertriglyceridemia as a cardiovascular risk factor Am J Cardiol 1998 81 (4A): 7B–12B.

    CAS  PubMed  Google Scholar 

  64. Austin MA, Mykkanen L, Kuusisto J, Edwards KL, Nelson C, Haffner SM, Pyorala K, Laakso M . Prospective study of small LDLs as a risk factor for non-insulin dependent diabetes mellitus in elderly men and women Circulation 1995 92: 1770–1778.

    CAS  PubMed  Google Scholar 

  65. Burke-Gaffney A, Hellewell PG . Tumour necrosis factor-alpha-induced ICAM-1 expression in human vascular endothelial and lung epithelial cells: modulation by tyrosine kinase inhibitors Br J Pharmac 1996 119: 1149–1158.

    CAS  Google Scholar 

  66. Miki I, Kusano A, Ohta S, Hanai N, Otoshi M, Masaki S, Sato S, Ohmori K . Histamine enhanced the TNF-alpha-induced expression of E-selectin and ICAM-1 on vascular endothelial cells Cellular Immunol 1996 171: 285–288.

    CAS  Google Scholar 

  67. Bhunia AK, Arai T, Bulkley G, Chatterjee S . Lactosylceramide mediates tumor necrosis factor-alpha induced intercellular adhesion molecule-1 expression (ICAM1) and the adhesion of neutrophil in human umbilical vein endothelial cells J Biol Chem 1998 273: 34349–34357.

    CAS  PubMed  Google Scholar 

  68. Ahima RS, Jeffery SF . Adipose tissue as an endocrine organ Trends Endocrinol Metab 2000 11: 327–332.

    CAS  PubMed  Google Scholar 

  69. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM . IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α and obesity-induced insulin resistance Science 1996 271: 665–668.

    CAS  PubMed  Google Scholar 

  70. Hotamisligil GS, Budavari A, Murray D, Spiegelman BM . Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes J Clin Invest 1994 94: 1543–1549.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Tappia PS, Troughton KL, Langley-Evans SC, Grimble RF . Cigarette smoking influences cytokine production and antioxidant defences Clin Sci 1995 88: 485–489.

    CAS  Google Scholar 

  72. Mendall MA, Patel P, Asante M, Ballam L, Morris J, Strachan DP, Camm AJ, Northfield TC . Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease Heart 1997 78: 273–277.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Crabtree JE . Role of cytokines in pathogenesis of Helicobacter pylori-induced mucosal damage Dig Dise Sci 1998 43 (Suppl 9): 46S–55S.

    CAS  Google Scholar 

  74. Watson C, Whittaker S, Smith N, Vora AJ, Dumonde DC, Brown KA . IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes Clin Exp Immunol 1996 105: 112–119.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscalla P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Cillberto G, Mantovani A . Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment Immunity 1997 6: 1–20.

    Google Scholar 

  76. Landsberg L . Diet, obesity and hypertension; a hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis Q J Med 1986 236: 1081–1090.

    Google Scholar 

  77. DeFronzo RA . The effect of insulin on renal sodium metabolism. A review with clinical implications Diabetologia 1981 21: 165–171.

    CAS  PubMed  Google Scholar 

  78. Stout RW . Insulin and atheroma. 20 years perspective Diabetes Care 1990 13: 631–655.

    CAS  PubMed  Google Scholar 

  79. Serne EH, Stehouwer CDA, ter Maaten JC, ter Wee PM, Rauwerda JA, Donker AJM, Gans ROB . Microvascular function relates to insulin sensitivity and blood pressure in normal subjects Circulation 1999 99: 896–602.

    CAS  PubMed  Google Scholar 

  80. Baron AD . Cardiovascular actions of insulin in humans. Implications for insulin sensitivity and vascular tone Ballière's Clin Endocrinol Metab 1993 7: 961–985.

    CAS  Google Scholar 

  81. Julius S, Gudbrandsson T, Jamerson K, Andersson O . The interconnection between sympathetics, microcirculation, and insulin resistance in hypertension Blood Pressure 1992 1: 9–19.

    CAS  PubMed  Google Scholar 

  82. Panahloo A, Yudkin JS . Diminished fibrinolysis in diabetes mellitus and its implication for diabetic vascular disease Coronary Artery Disease 1996 7: 723–731.

    CAS  PubMed  Google Scholar 

  83. Juhan Vague I, Roul C, Alessi MC, Ardissone JP, Heim M, Vague P . Increased plasminogen activator inhibitor activity in non insulin dependent diabetic subjects: relationship with plasma insulin Thromb Haemostat 1989 61: 370–373.

    CAS  Google Scholar 

  84. Rimm EB, Chan J, Stampfer MJ et al. Prospective study of cigarette smoking, alcohol use and the risk of diabetes in man Br Med J 1995 310: 555–559.

    CAS  Google Scholar 

  85. Janzon L, Berntorp K, Hanson M, Lindell SE, Trell E . Glucose tolerance and smoking: a population study of oral and intravenous glucose tolerance test in middle-aged men Diabetologia 1983 25: 86–88.

    CAS  PubMed  Google Scholar 

  86. Ko GTC, Cockram CS, Chan JCN . Smoking and diabetes in Chinese men Postgrad Med J 2000 77: 240–243.

    Google Scholar 

  87. Persson PG, Carlsson S, Svanstrom L, Ostenson CG, Efendic S, Grill V . Cigarette smoking, oral moist snuff use and glucose intolerance J Intern Med 2000 248: 103–110.

    CAS  PubMed  Google Scholar 

  88. Corretti MC, Plotnick GD, Vogel R . Smoking correlates with flow mediated brachial artery vasoactivity but not cold pressor vasoactivity in men with coronary artery disease Int J Cardiac Imag 1998 14: 11–17.

    CAS  Google Scholar 

Download references

Acknowledgements

We are grateful for the help of Mairi Gould for the work on the screening phase of the Goodinge Study and Maryam Fernández for work on the recall phase, to Dr John Griffin in performing the assays of cytokines and Dr Geoffrey Ridgway, Dr Nicola Brink and Dr John Holton for antibody titre assays. We thank Ms Christine Andrés for microalbumin and PAI-1 activity assays and Dr Vidya Mohamed-Ali for measurement of insulin and proinsulin-like molecules. We also thank Professor Melissa Austin for measuring the LDL-particle size. Aspects of this study were supported by grants from the Wellcome Trust (12441/1.5) and British Heart Foundation (PG92133) and a Program Grant from Diabetes UK. Dr Stehouwer is supported by a fellowship from the Diabetes Fonds Netherland and the Netherlands Organisation for Scientific Research (NWO) and Dr Emeis by Grant 28-2623 from the Praeventiefonds. We thank Professor Melissa Austin for measuring the LDL particle size.

Author information

Authors and Affiliations

  1. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong, China

    JCN Chan & PCY Tong

  2. Department of Applied Social Science, The City University, Hong Kong, China

    JCK Cheung

  3. Department of Medicine, Academic Hospital Vrije Universiteit and the Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, 1081 HV, The Netherlands

    CDA Stehouwer

  4. Gaubius Laboratory, TNO-PG, Leiden, 2301 CE, The Netherlands

    JJ Emeis

  5. Department of Medicine, Tai Po Alice Ho Nethersole Hospital, Tai Po, Hong Kong, China

    GTC Ko

  6. Department of Medicine, University College London Medical School, London, UK

    JS Yudkin

Authors
  1. JCN Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. JCK Cheung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. CDA Stehouwer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. JJ Emeis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. PCY Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. GTC Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. JS Yudkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to JCN Chan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chan, J., Cheung, J., Stehouwer, C. et al. The central roles of obesity-associated dyslipidaemia, endothelial activation and cytokines in the Metabolic Syndrome—an analysis by structural equation modelling. Int J Obes 26, 994–1008 (2002). https://doi.org/10.1038/sj.ijo.0802017

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802017

Keywords

This article is cited by

Search

Advanced search

Quick links