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Submitted on June 17, 2005
Accepted on September 23, 2005
Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0607, USA; Department of Epidemiology and Public Health, University College London Medical School, 1-19 Torrington Place, London WC1E 6BT, UK
* To whom correspondence should be addressed. E-mail: ebarrettconnor{at}ucsd.edu.
Context: Ghrelin may be one of the pathophysiological mechanisms underlying risk factor clustering observed in the metabolic syndrome, but this has not been investigated.
Objective: To study the association between ghrelin and the metabolic syndrome and identify social and behavioral determinants of ghrelin.
Design: Cross-sectional.
Setting: Rancho Bernardo Study.
Participants: 1513 men and women aged 51-90 yr in 1984-87.
Outcomes: Total ghrelin, measured by RIA, and the metabolic syndrome, defined using ATPIII diagnostic criteria.
Results: Levels of ghrelin (mean (SD) did not differ between the 848 men (1451 pg/ml (532)) and the 665 women (1459 pg/ml (672)), or by age. Education, alcohol intake and smoking history were each significantly and positively associated with ghrelin in a dose related manner, independent of body mass index (BMI). Compared with participants in the lowest third of ghrelin, the age and sex adjusted odds of having the metabolic syndrome was 18% lower in the middle and 53% lower in the highest third. This corresponds to a 21% decrease per SD increase of ghrelin (odds ratio (95% confidence interval) 0.79 (0.69; 0.89), p 
0.001); this was attenuated to 13% (0.87 (0.75; 1.01), P = 0.07), after adjustment for BMI. Of the 5 metabolic syndrome components, only the association between ghrelin and HDL-cholesterol was independent of BMI. A significant association that was independent of BMI was also observed between insulin and ghrelin.
Conclusions: Ghrelin levels are influenced by lifestyle factors. The inverse association between endogenous ghrelin and the metabolic syndrome is largely explained by the strong ghrelin-BMI association.
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