Soluble transferrin receptor and risk of type 2 diabetes in the obese and nonobese

BACKGROUND: Studies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in nonobese individuals. Therefore, the aim of this study was to assess the relationship between sTfR and the risk of T2DM in obese and nonobese subjects. DESIGN: A nested case-control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 nonobese, and 306 individually matched controls, 138 obese and 166 nonobese, who did not develop T2DM for a median 6-year follow-up (interquartile range: 3·9-6·5) was conducted using data from the PREvention with MEDiterranean Diet (PREDIMED) cohort (http://www.controlled-trials.com/ISRCTN35739639). Cases and controls were matched for age (≤ 67 vs. > 67 years), gender, dietary intervention group and BMI (≤ 27 vs. > 27 kg/m2 ). RESULTS: Waist circumference is the main determinant of sTfR concentrations in the whole sample (β = 0·476, P < 0·001), in the obese (β = 0·802, P < 0·001) and the nonobese (β = 0·455, P = 0·003). Furthermore, sTfR is directly associated with the risk of T2DM in obese individuals (OR = 2·79; 95% CI: 1·35-5·77, P = 0·005) and inversely associated in nonobese individuals (OR = 0·40; 95% CI: 0·20-0·79, P = 0·015). CONCLUSIONS: The association between sTfR levels and risk of T2DM in a population at high cardiovascular risk depend on the presence or absence of obesity. While in nonobese subjects elevated sTfR levels are associated with a decreased risk of developing T2DM, in obese subjects the risk increases. This suggests that obesity alters the relatio