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

Purpose

It is unclear whether vitamin D provides any benefit against the pro-inflammatory
effects of homocysteine in elderly patients with type 2 diabetes mellitus (T2DM).

Methods

We 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).

Findings

Significant 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.

Implications

Serum 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.

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