The negative association between plasma ghrelin and IGF-I is modified by obesity, insulin resistance and type 2 diabetes

Abstract

Aims/hypothesis: Ghrelin is a natural growth hormone-releasing peptide thought to be involved in the regulation of energy metabolism. The recent studies concerning the association between ghrelin and insulin-like growth factor-I (IGF-I) concentrations have shown either negative correlation or no correlation at all. The aims of this study were to clarify the association between ghrelin and IGF-I concentrations in a large cohort and to characterize whether obesity, insulin resistance and type 2 diabetes affect this association. Methods: We analysed fasting plasma ghrelin and IGF-I concentrations of 1,004 middle-aged subjects of the population-based OPERA study. Insulin resistance was estimated using QUICKI. Results: IGF-I concentrations were negatively associated with ghrelin concentrations in the analysis of all subjects before (β=-0.32, p<0.001) and after adjustments for BMI, insulin levels, sex and age (β=-0.40, p<0.001). The association was particularly strong in males and in the higher BMI tertiles. The degree of association varied in relation to the glycaemic status: no insulin resistance: r2=6.5% (p<0.001), insulin resistance without type 2 diabetes: r2=21.0% (p<0.001), type 2 diabetes: r2=25.4 (p<0.001). IGF-I levels explained larger proportion (r2=9.8%) of the variation in ghrelin concentrations compared to fasting insulin concentration (r2=3.0%) and BMI (r2=1.5%). Conclusions/interpretation: There is a negative and independent association between ghrelin and IGF-I concentrations in middle-aged subjects. The interaction between IGF-I and ghrelin is modified by obesity, IR and type 2 diabetes. Further studies are warranted to elucidate the role of ghrelin in the development of these states. © Springer-Verlag 2005.