Association of grelin and peptide YY with insulin resistance and bone density in the Newfoundland population

Abstract

Ghrelin and Peptide YY (PYY) are two important gut hormones involved in the regulation of food intake and energy homeostasis. Recently, data mainly from in vitro and animal models have suggested that these hormones may play a role in the regulation of glucose homeostasis and bone density. However, previous human studies were performed on a small sample size, and their results are inconclusive. Moreover, important confounding factors were not controlled in these studies. -- In the first project, I addressed the association of circulating ghrelin with insulin resistance. A total of 2082 subjects from the Complex Diseases in the Newfoundland population: Environment and Genetics (CODING) study, participated in this investigation. Partial correlation analyses revealed that circulating ghrelin had significant inverse associations with insulin level and insulin resistance indices in the entire cohort (insulin: r = -0.09, p < 0.001 ; HOMA-IR: r = -0.08, p < 0.001 ; HOMA-β: r = -0.1 , p < 0.001 ; and QUICKI: r = 0.08, p < 0.001) and also in men and women separately. These correlations were independent of age, percentage of trunk fat, and HDL-cholesterol. -- In the second project, I investigated the relationship between circulating ghrelin and PYY and bone density using the same cohort, by controlling major confounding factors: age, BMI, physical activity, alcohol consumption, and smoking. A total of 2257 adult subjects were recruited in this study. Our results suggest a beneficial effect of circulating ghrelin level on bone density indices (L2-L4 BMD, L2-L4 Z-score, femoral neck BMD, femoral neck Z-score, total hip BMD, and total hip Z-score) in women. This effect was independent of the major confounding factors. However, we did not find evidence that PYY is significantly associated with the bone density parameters.