Vitamin D Provides Benefit Based on the Proinflammatory Effects of Homocysteine in Elderly Patients With Type 2 Diabetes Mellitus

Abstract

PurposeIt is unclear whether vitamin D provides any benefit against the pro-inflammatory effects of homocysteine in elderly patients with type 2 diabetes mellitus (T2DM). MethodsWe compared lymphocyte counts for CD3, CD19, CD4, and CD8 subsets between elderly (age ≥65 years) T2DM patients (n = 5098) and nondiabetes control subjects (n = 20,590) based on the serum concentrations of homocysteine and total vitamin D (calcidiol + calcifediol [total vitamin D, TVD]; <20, 20-30, and >30 ng/mL). FindingsSignificant variation in CD19 (P = 0.019), CD4 (P = 0.015), and CD8 (P < 0.001) were associated with serum TVD in T2DM patients with homocysteine ≤15 μmol/L, whereas CD3 (P = 0.003) and CD8 (P = 0.019) varied in control subjects with homocysteine ≤15 μmol/L. In T2DM patients with high homocysteine (>15 μmol/L) levels, significant variation based on serum TVD occurred in CD19 only (P = 0.024), whereas CD3 (P = 0.016) and CD4 (P = 0.001) varied in control subjects with high homocysteine concentrations. ImplicationsSerum TVD influences variation in CD3, CD19, CD4, and CD8 lymphocyte subsets based on the serum homocysteine concentration in elderly T2DM patients and nondiabetic individuals with moderate to high homocysteine concentrations. The effect of TVD is partially attenuated in individuals with high homocysteine concentrations, with greater attenuation occurring in patients with T2DM. Differences in the variation of lymphocyte subsets between nondiabetes subjects with moderate homocysteine concentrations and those with high homocysteine concentrations constitute a shift from CD8-positive cells to CD4-positive cells, suggesting a change in TH1/TH2 balance based on TVD and homocysteine concentrations that is absent in diabetes cases with high homocysteine concentrations.