Effect of oral versus parenteral vitamin D3 supplementation on nuclear factor-κB and platelet aggregation in type 2 diabetic patients

Abstract

Platelet hyperactivity is one of the key factors implicated in the development and progression of diabetic vascular complications. Activated platelets mediate leukocyte recruitment that further enhances inflammatory responses in vascular wall ultimately resulting in atherosclerotic complications. Since vitamin D insufficiency is highly prevalent in diabetics, we aimed to evaluate the effect of three dosage forms of vitamin D supplementation on lipid profile, NF-κB, platelet aggregation, and platelet calcium content in type 2 diabetic patients. Type 2 diabetic patients were randomized to receive daily (4000 IU/day) or weekly (50 000 IU/week) oral vitamin D3 for 3 months. Another group received a single parenteral dose (300 000 IU) of vitamin D3, whereas the control group received their antidiabetic drug(s) alone. Serum 25(OH)D, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol, NF-κB, and platelet aggregation were measured at the beginning and 3 months after vitamin D supplementation. Platelet calcium content was evaluated by measuring the fluorescence intensity of Rhod-2-stained platelets by confocal fluorescence microscopy. Results showed that serum 25(OH)D3 levels significantly increased in all vitamin D3-treated groups. However, the mean level for parenteral treated group was significantly lower than oral-treated groups. Oral and parenteral treatment were also able to decrease NF-κB level, platelet aggregation, and platelet calcium content. However, both oral doses of vitamin D3 were superior to the single parenteral dose. In conclusion, restoring normal levels of vitamin D is an important determinant to maintain normal platelet function and reduce inflammation. Nevertheless, further long-term studies are still needed.