Ghrelin and the Metabolic Syndrome in Older Adults

Abstract
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: The objective of this work was to study the association between ghrelin and the metabolic syndrome and identify social and behavioral determinants of ghrelin. Design: This was a cross-sectional study. Setting: The setting of this work was the Rancho Bernardo Study. Participants: Study subjects included 1513 men and women, aged 51–90 yr in 1984–1987. Outcomes: Total ghrelin, measured by RIA, and the metabolic syndrome, defined using Adult Treatment Panel III diagnostic criteria, were the outcome measures. Results: Levels of ghrelin (mean ± sd) did not differ between the 848 men (1451 ± 532 pg/ml) and the 665 women (1459 ± 672 pg/ml) 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 with the lowest third of ghrelin levels, the age- and sex-adjusted odds of having the metabolic syndrome were 18% lower in the middle third and 53% lower in the highest third. This corresponds to a 21% decrease per sd increase in ghrelin (odds ratio, 0.79; 95% confidence interval, 0.69, 0.89; P ≤ 0.001); this was attenuated to 13% (odds ratio, 0.87; 95% confidence interval, 0.75, 1.01; P = 0.07), after adjustment for BMI. Of the five metabolic syndrome components, only the association between ghrelin and high-density lipoprotein cholesterol was independent of BMI. A significant association 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.