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

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 middleaged 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 ( = - 0.32, p< 0.001) and after adjustments for BMI, insulin levels, sex and age (beta =- 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: r(2)= 6.5% ( p< 0.001), insulin resistance without type 2 diabetes: r(2)= 21.0% ( p< 0.001), type 2 diabetes: r(2)= 25.4 ( p< 0.001). IGF- I levels explained larger proportion ( r(2)= 9.8%) of the variation in ghrelin concentrations compared to fasting insulin concentration ( r(2)= 3.0%) and BMI ( r(2)= 1.5%). Conclusions/ interpretation: There is a negative and independent association between ghrelin and IGF- I concentrations in middleaged 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.