We measured the levels of bone turnover markers (BTMs) in patients with early diabetic nephropathy from type 2 diabetes mellitus (T2DM), and investigated the associations of BTMs with adipokines, serum fibroblast growth factor-21 (FGF21) and osteonectin.
The results suggest the following molecular etiopathophysiology of DN: (i) hyperglycemia upregulates IGF2, which initiates PTEN, a regulator of IGF2 signaling; (ii) loss of this IGF2-PTEN feedback loop causes changes that are characteristic of DN; and (iii) lowered expression of the repair modulator SPARC results in the development and/or progression of DN.