People with type 2 diabetes have been reported to have more vitamin D deficiency than people without. Vitamin D may play a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity.
 

    Talaei et al. (1) evaluated the effects of vitamin D supplementation on insulin resistance in people with type 2 diabetes. This study recruited 100 people with type 2 diabetes (70 women and 30 men, 30–70 years old). Participants were assessed for clinical and biochemistry. Study participants received 50,000 IU of vitamin D3 orally per week for eight weeks. All measurements were compared between baseline and at the end of the vitamin D supplementation.

    Among all the study participants, 24% of them were vitamin D deficient [serum 25(OH)D ≤ 20 ng/ml(50 nmol/l)]. Mean serum 25 (OH) D concentration was 43.03± 19.28 ng/ml (107.5±48.2 nmol/l). The results at baseline and at the end for fasting blood glucose were 138.48±36.74 and 131.02±39 mg/dl (p=0.05); for insulin, 10.76±9.46 and 8.6±8.25 μIu/ml (p=0.028); and for HOMA-IR, 3.57±3.18 and 2.89±3.28 (p=0.008) respectively. Vitamin D level 25(OH)D (ng/ml) was increased from 43.03±19.28 at baseline to 60.12±17.2 at the end of supplementation (p=0.02). These results showed that vitamin D supplementation could significantly improve fasting blood glucose, insulin, and HOMA-IR, reducing insulin resistance in type 2 diabetic people.

    The authors also reported an inverse relationship between the final fasting blood glucose level and basal 25(OH) level. In other words, higher basal 25(OH) D was associated with lower final fasting blood glucose levels. This means that those who had a higher basal 25(OH)-D level could benefit more from vitamin D intake to lower final fasting blood glucose. The authors believed that at lower vitamin D levels, the available vitamin D would be limited to the use for the bone and muscles, any non-skeletal effects of vitamin D, such as its effect on insulin resistance, would appear only in higher vitamin D levels. Their data showed that the effect of vitamin D on insulin resistance was significant when vitamin D level was 40–60 ng/ml (100–150 nmol/l), and in the lower and upper vitamin D levels out of this range, it did not impact insulin resistance (1).

    Cojic et al. (2) recruited people with type 2 diabetes on standard metformin therapy (n=130) to be randomized to receive either vitamin D supplementation or to have continued with metformin only for 6 months. The participants in the treatment group who were vitamin D deficient [defined as serum levels of 25(OH)D ≤ 50 nmol/L] were asked to take 50 000 IU of vitamin D3 weekly during the first 3 months and 14 000 IU weekly for the next 3 months. The participants in the treatment group whose 25(OH)D levels were > 50 nmol/L were asked to take 14 000 IU weekly until the end of the study.

    The study found that the recommended doses of vitamin D significantly decreased the level of HbA1c after 3 as well as after 6 months of vitamin D supplementation in people with type 2 diabetes treated with metformin, compared to the metformin group. There was also a significant decrease in advanced oxidation protein product levels over the 3 months when higher vitamin D doses were given. However, the effects of vitamin D on insulin resistance index HOMA-IR, malondialdehyde levels (fat oxidation biomarker), and Thiobarbituric acid-reactive substances (TBARS, oxidative stress biomarker) index were not found statistically significant.

    According to the authors, this was the first study with an individual dosing plan for patients regarding 25(OH)D levels according to the European Endocrine Society guidelines. The daily doses proposed were 7142 IU (50 000 IU weekly) for vitamin D deficient patients and 2000 IU for patients who had 25(OH)D levels > 50 nmol/L. The dose of 2000 IU was not sufficient to provide 25(OH)D levels beyond 100 nmol/L, which was believed to be crucial for extra-skeletal effects. This could explain why the results did not maintain a significant effect of vitamin D on fasting insulin and insulin resistance HOMA-IR levels over the six months. Talaei et al. showed that the effect of vitamin D on insulin resistance was significant only when the vitamin D concentration was between 100 and 150 nmol/L (1).

    In a double-blinded, 3-study center, randomized, placebo-controlled trial, participants were randomized to receive active vitamin D (eldecalcitol, a vitamin D analog, 0.75 μg per day; n=630) or a matching placebo (n=626) for three years (3). A standard dose of 0.75 µg of eldecalcitol is used to prevent and treat osteoporosis in Japan. The participants were aged 30 years and older and had impaired glucose tolerance defined using a 75 g oral glucose tolerance test and glycated hemoglobin level. After adjustment for confounding factors, eldecalcitol significantly lowered the development of diabetes (hazard ratio 0.69, 0.51 to 0.95; p=0.020), meaning a 31% reduced risk. In addition, eldecalcitol showed its beneficial effect among the participants with the lower level of basal insulin secretion (hazard ratio 0.41, 0.23 to 0.71; p=0.001). Bone mineral densities of the lumbar spine and femoral neck, and serum osteocalcin concentrations were significantly increased in the group that received eldecalcitol compared to those in the placebo group (all p<0.001).

    The proposed mechanisms of vitamin D's beneficial effects may occur on different levels. Vitamin D receptors have been found in various cell types, including pancreatic beta cells, and active vitamin D is reportedly involved in insulin biosynthesis and secretion. By acting as an immune modulator, vitamin D can regulate immunity and decrease the inflammatory response thus reducing the death of pancreatic beta cells. Vitamin D also possesses antioxidant potential, and as a lipophilic substance, it can work in cell membranes and lipoproteins as a free radical scavenger and antioxidant.

    Oxidative stress is strongly associated with type 2 diabetes, it influences insulin peripheral sensitivity and insulin secretory response. Hyperglycemia contributes to the generation of reactive oxygen species (ROS), through glucose autoxidation and consequent non-enzymatic glycation of proteins in diabetes. Vitamin D supplementation can be very beneficial for diabetic people to improve insulin resistance and reduce oxidative stress.

    Vitamin D is essential for maintaining bone and skeletal health. For people with diabetes, vitamin D supplementation may help reduce insulin resistance. For those who do not want to become diabetic, taking vitamin D supplements may reduce the risk of becoming one.

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References:

1. Talaei, A., Mohamadi, M., & Adgi, Z. (2012). The effect of vitamin D on insulin resistance in patients with type 2 diabetes. Diabetology & Metabolic Syndrome, 5, 8. https://doi.org/10.1186/1758-5996-5-8

2. Cojic, M., Kocic, R., Klisic, A., & Kocic, G. (2020). The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.610893

3. Kawahara, T. et al. (2022). Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population. BMJ 2022; 377:e066222. doi: https://doi.org/10.1136/bmj-2021-066222