Relationships Between Erythrocyte Osmotic Fragility and Vitamin C Nutriture in Adults with or without Type 2 Diabetes

Diabetes is the 7th leading cause of death globally. In 2018, 34.2 million Americans had type 2 diabetes. Many symptoms of diabetes are similar to those of scurvy or vitamin C deficiency. Vitamin C marginality and inadequacy are more prevalent in Type 2 Diabetes/prediabetes than with normal glucose tolerance. Intracellular vitamin C inadequacy is suspected due to competition between dehydroascorbic acid and glucose at GLUT 1 and 3 cellular receptors. Erythrocyte osmotic fragility is noted in Gulo -/- knockout mice unable to synthesize endogenous vitamin C. The ascorbate deficient red blood cells presented with low cytoskeletal B-spectrin, spherocyte appearance, and impaired deformability. This cross-sectional study investigated the relationships between diabetes status, erythrocyte osmotic fragility, and serum vitamin C status. Participants were aged 18-65, non-smoking, reported no unresolved health complications, and denied prior vitamin C supplementation. Those with T2D indicated diagnosis of >1 year. All participants provided written informed consent and the study was approved by the local Institutional Review Board in January 2021. Participants provided one fasted blood sample. Erythrocyte osmotic fragility was measured via UV/Vis spectrophotometry with various concentrations of sodium chloride (0.85% - 0.10%) to induce osmotic stress. In addition, plasma was extracted and mixed 1:1 with 10% (w/v) metaphosphoric acid in 2 mmol/L disodium EDTA and centrifuged. The supernatant was stored at -80°C until analysis with isocratic reverse-phase UV-HPLC separation. Participant characteristics did not differ significantly between groups apart from age (p< 0.01) and HbA1c (p=0.002). Data are presented for adults with T2D (n=14; 36% female; 55.5±8.2 y; 31.5±9.0 kg/m2; HbA1c: 7.4±1.9%; plasma vitamin C: 36.0±12.2 uM) and without T2D (n=16; 69% female; 38.7±13.5 y; 26.8±6.6 kg/m2; A1c: 5.4±0.3%; plasma vitamin C: 34.8±10.9uM). Erythrocyte osmotic fragility was significantly elevated (+4.4% hemolysis) in adults without T2D at 0.35% saline (p=0.039). Greater VC status (>30 uM) was associated with lower hemolysis at 0.35% NaCl (p=0.031). Erythrocyte osmotic stability was linked to greater vitamin C intake at 0.20% saline in those without T2D (p =0.019). In this pilot study, vitamin C status did not differ significantly by diabetes status. Vitamin C status was directly linked to erythrocyte osmotic stability in adults without T2D.