Vitamin D and L-cysteine levels correlate positively with GSH and negatively with insulin resistance levels in the blood of type 2 diabetic patients

BACKGROUND/OBJECTIVES: Vitamin D, L-cysteine (LC) and glutathione (GSH) levels are lower in the blood of diabetic patients. This study examined the hypothesis that the levels of vitamin D and LC correlate with those of GSH in the blood of type 2 diabetic patients (T2D), and that vitamin D and LC upregulate glutamate–cysteine ligase (GCLC), which catalyzes GSH biosynthesis, in cultured monocytes. SUBJECTS/METHODS: Fasting blood was obtained after written informed consent from T2D (n=79) and healthy controls (n=22). U937 monocytes were pretreated with 1,25 (OH)(2) vitamin D (0–25 nM) or LC (0–500 μM) for 24 h and then exposed to control or high glucose (25 mM) for 4 h. RESULTS: Plasma levels of vitamin D, LC, GSH and GCLC protein were significantly lower in T2D versus those in age-matched healthy controls. Multiple linear regression analyses and adjustment for body weight showed a significant positive correlation between plasma levels of vitamin D (r=0.26, P=0.05) and LC (r=0.81, P=0.001) and that of GSH, and between LC and vitamin D (r=0.27, P=0.045) levels. Plasma levels of GSH (r=−0.34, P=0.01) and LC (r=−0.33, r=0.01) showed a negative correlation with triglyceride levels. Vitamin D correlated inversely with HbA(1C) (−0.30, P=0.01) and homeostatic model assessment insulin resistance (r=−0.31, P=0.03), which showed a significant positive correlation with triglycerides (r=0.44, P=0.001) in T2D. Cell culture studies demonstrate that supplementation with vitamin D and LC significantly increased GCLC expression and GSH formation in control and high-glucose-treated monocytes. CONCLUSIONS: This study suggests a positive relationship between the concentrations of the micronutrients vitamin D and LC and that of GSH. Some of the beneficial effects of vitamin D and LC supplementation may be mediated by an increase in the levels of GSH and a decrease in triglyceride levels in T2D patients.