Impact of the Adipokine Adiponectin and the Hepatokine Fetuin-A on the Development of Type 2 Diabetes: Prospective Cohort- and Cross-Sectional Phenotyping Studies

Among adipokines and hepatokines, adiponectin and fetuin-A were consistently found to predict the incidence of type 2 diabetes, both by regulating insulin sensitivity.To determine to what extent circulating adiponectin and fetuin-A are independently associated with incident type 2 diabetes in humans, and the major mechanisms involved.Relationships with incident diabetes were tested in two cohort studies: within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (628 cases) and the Nurses' Health Study (NHS; 470 cases). Relationships with body fat compartments, insulin sensitivity and insulin secretion were studied in the Tübingen Lifestyle Intervention Program (TULIP; N = 358).) associated with insulin sensitivity, circulating fetuin-A (r = −0.37, p = 0.0004), but not adiponectin, associated with insulin secretion in subjects with impaired glucose tolerance.We provide novel information that adiponectin and fetuin-A independently of each other associate with the diabetes risk. Furthermore, we suggest that they are involved in the development of type 2 diabetes via different mechanisms, possibly by mediating effects of their source tissues, expanded adipose tissue and nonalcoholic fatty liver