Genetic Predisposition and Dietary Factors in Relation to Adiponectin and Insulin Resistance

Abstract

Insulin resistance is a critical condition to the development of type 2 diabetes and adiponectin, a hormone secreted by the adipose cells, has attracted much attention for its insulin-sensitizing and anti-diabetic effects. We aimed to have a better understanding of the roles of ethnicity, genetic variants and dietary factors in relation to adiponectin and insulin resistance. Using path analysis, we examined potential mediators including body fatness, adiponectin levels, and inflammation for the extent they mediate the ethnic differences in insulin resistance among Singaporean Chinese, Malays and Indians. In a genome-wide association analysis to identify genetic variants that influence adiponectin levels, we demonstrated an important role of the gene CDH13 on adiponectin levels and metabolic profile in East Asian populations. We also investigated the positive association between adiponectin and insulin sensitivity by a Mendelian randomization design on a cohort of Swedish men, and our results suggested that this relationship could be causal. Further, our longitudinal analysis in this cohort showed no substantial association of selenium status with insulin sensitivity, insulin secretion, or risk of diabetes in the older individuals. This does not support a role for selenium supplementation as a broad approach for the prevention of diabetes.