Circulating Soluble Transferrin Receptor According to Glucose Tolerance Status and Insulin Sensitivity

Abstract

The relationships between iron metabolism and type 2 diabetes are bidirectional: iron affects glucose metabolism and glucose metabolism impinges on several iron metabolic pathways. The mechanisms of these interactions depend on poorly known factors. We aimed to study the contribution of the serum soluble transferrin receptor (sTfR). Circulating sTfR was evaluated in 221 men (97 with normal glucose tolerance [NGT], 36 with impaired glucose tolerance, and 88 with type 2 diabetes). In a subset of these subjects, glucose tolerance (oral glucose tolerance test [OGTT]), minimal model-derived insulin sensitivity, and sTfR during the OGTT were also evaluated. Men with altered glucose tolerance showed significantly increased sTfR (9.4 +/- 4.4 vs. 8.2 +/- 2.6 microg/ml, P = 0.02) and higher serum ferritin than men with NGT. Serum sTfR was negatively associated with serum ferritin (r = -0.16, P = 0.02). sTfR correlated with several clinical and metabolic variables such as systolic blood pressure, glycated hemoglobin, and glucose and insulin values during OGTT. Insulin sensitivity was also negatively associated with sTfR in NGT and nonobese subjects. BMI (P = 0.01), serum ferritin (P = 0.025), and insulin sensitivity (P < 0.0001) contributed independently to 21% of sTfR variance. Serum sTfR concentration did not significantly change during the OGTT. Both insulin sensitivity and glucose tolerance status are significantly associated with serum sTfR concentrations, although insulin sensitivity predicts independently circulating sTfR, mainly in subjects with NGT. The implications of the interrelationships between iron and glucose metabolism should be investigated further.