PMID- 12080455
OWN - NLM
STAT- MEDLINE
DCOM- 20020809
LR  - 20171116
VI  - 26
IP  - 7
DP  - 2002 Jul
TI  - The central roles of obesity-associated dyslipidaemia, endothelial activation and 
      cytokines in the Metabolic Syndrome--an analysis by structural equation 
      modelling.
PG  - 994-1008
AB  - 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 TNFalpha), 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 TNFalpha 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 TNFalpha were correlated with age, male 
      gender, obesity indexes and markers of endothelial activation. Only IL-6 was 
      associated with smoking while TNFalpha was correlated with hyperinsulinaemia. In 
      the TNFalpha model, 61% of the obesity variance was explained by male gender, 36% 
      of TNFalpha 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 TNFalpha, 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 TNFalpha 
      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.
FAU - Chan, J C N
AU  - Chan JC
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The 
      Prince of Wales Hospital, Shatin, NT, Hong Kong, China. jchan@cuhk.edu.hk
FAU - Cheung, J C K
AU  - Cheung JC
FAU - Stehouwer, C D A
AU  - Stehouwer CD
FAU - Emeis, J J
AU  - Emeis JJ
FAU - Tong, P C Y
AU  - Tong PC
FAU - Ko, G T C
AU  - Ko GT
FAU - Yudkin, J S
AU  - Yudkin JS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Obes Relat Metab Disord
JT  - International journal of obesity and related metabolic disorders : journal of the 
      International Association for the Study of Obesity
JID - 9313169
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aging
MH  - Blood Pressure
MH  - Body Composition
MH  - Body Constitution
MH  - Body Mass Index
MH  - Cholesterol, HDL/blood
MH  - Cholesterol, LDL/blood
MH  - Cytokines/*physiology
MH  - Endothelium, Vascular/*physiopathology
MH  - Female
MH  - Fibrinolysis
MH  - Humans
MH  - Hyperinsulinism/complications
MH  - Hyperlipidemias/*complications
MH  - Inflammation/complications
MH  - Interleukin-6/blood
MH  - Male
MH  - *Metabolic Syndrome
MH  - Middle Aged
MH  - Obesity/*complications/physiopathology
MH  - Sex Characteristics
MH  - Smoking/adverse effects
MH  - Triglycerides/blood
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 2002/06/25 10:00
MHDA- 2002/08/10 10:01
CRDT- 2002/06/25 10:00
PHST- 2001/01/25 00:00 [received]
PHST- 2002/01/21 00:00 [revised]
PHST- 2002/02/04 00:00 [accepted]
PHST- 2002/06/25 10:00 [pubmed]
PHST- 2002/08/10 10:01 [medline]
PHST- 2002/06/25 10:00 [entrez]
AID - 10.1038/sj.ijo.0802017 [doi]
PST - ppublish
SO  - Int J Obes Relat Metab Disord. 2002 Jul;26(7):994-1008. doi: 
      10.1038/sj.ijo.0802017.