Aml Mohamed Nada,1 Dalia Shaheen2 1Faculty of Medicine, Department of Internal Medicine, 2Faculty of Medicine, Department of Medical Biochemistry, Mansoura University, Mansoura, Egypt Background and purpose: To investigate the effects of vitamin D supplementation on glucose homeostasis and lipid profile in type 2 diabetic patients who have vitamin D deficiency.Patients and methods: One hundred twenty-five type 2 diabetic patients taking oral hypoglycemic agents as mono- or combination therapy were recruited from the diabetes and endocrinology clinic. Subject demographics, duration of diabetes, antidiabetic medication, body mass index (BMI), pulse, and blood pressure (BP) were assessed. Laboratory measurements of serum vitamin D3 level, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and lipid profile were measured. Homeostatic model assessment-insulin resistance (HOMA-IR) was calculated whenever fasting insulin (FI) was available. Forty-one patients (27 males and 14 females) were started on cholecalciferol replacement–45,000 units once weekly for 8 weeks and then 22,500 units once weekly for 16 weeks. Calcium carbonate tablets 500 mg once daily were also prescribed for the initial 2 months of treatment. Measured variables were reassessed after 6 months of replacement therapy. During the trial, subjects were instructed not to change their diabetes drugs or lifestyle.Results: No significant association was found between vitamin D3 level and any of the measured variables apart from a significant positive correlation with blood urea nitrogen. Vitamin D3 replacement was associated with a significant increase in its level (14.0±4.0 vs 31.0 vs 7.9 ng/mL, P<0.001). This was associated with a significant reduction of HbA1c (7.9±1.7 vs 7.4%±1.2%, P=0.001) and FPG (9.1±4.3 vs 7.9±2.4 mmol/L, P=0.034). Mean reduction of HbA1c was 0.54% and that of FPG was 1.22 mmol/L. FI, c-peptide and insulin resistance (IR) were reduced but this was statistically insignificant (P=0.069, 0.376, 0.058, respectively). FI decreased by 22%, HOMA-IR by 27.6%, and c-peptide by 1.83%. Total cholesterol, low-density lipoprotein cholesterol, parathyroid hormone, alkaline phosphatase, serum creatinine, and pulse rate significantly decreased (4.3±0.9 vs 4.0±0.9 mmol/L, P=0.036; 2.5±0.8 vs 2.2±0.8 mmol/L, P=0.018; 4.6±2.1 vs 3.5±1.8 pmol/L, P=0.001; 82.1±26.2 vs 66.2±19.5 U/L, P<0.001; 74.6±15.6 vs 70.7±14.7 µmol/L, P=0.047; and 81.6±11.9 vs 77.5±12.0 bpm, P=0.045, respectively). Triglycerides and high-density lipoprotein cholesterol, both systolic and diastolic BP, and BMI did not show significant change.Conclusion: Cholecalciferol helps improve blood glucose control and cholesterol profile in vitamin D3-deficient type 2 diabetic patients. Keywords: vitamin D, type 2 diabetes, HbA1c, cholesterol, creatinine, parathyroid hormone