Sodium In The Dermis Colocates To Glycosaminoglycan Scaffold, With Diminishment In Type 2 Diabetes Mellitus

BACKGROUND. Dietary sodium intake mismatches urinary sodium excretion over prolonged periods. Our aims were to localize and quantify electrostatically bound sodium within human skin using triple-quantum-filtered (TQF) protocols for MRI and magnetic resonance spectroscopy (MRS) and to explore dermal sodium in type 2 diabetes mellitus (T2D).METHODS. We recruited adult participants with T2D (n = 9) and euglycemic participants with no history of diabetes mellitus (n = 8). All had undergone lower limb amputations or abdominal skin reduction surgery for clinical purposes. We used 20 mu m in-plane resolution H-1 MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, Na-23 TQF MRI/MRS to explore distribution and quantification of freely dissolved and bound sodium, and inductively coupled plasma mass spectrometry to quantify sodium in selected skin samples.RESULTS. Human dermis has a preponderance (>90%) of bound sodium that colocalizes with the glycosaminoglycan (GAG) scaffold. Bound and free sodium have similar anatomical locations. T2D associates with a severely reduced dermal bound sodium capacity.CONCLUSION. We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal "third space repository" for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.