A Summary of the article on the “Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial”
Background
The study by J. I. Aguayo-Ruiz et al (2022) was published in Diabetology & Metabolic Syndrome in August 2020. Patients with Type 2 Diabetes Mellitus (T2DM) are characterized by chronic hyperglycemia resulting from reduced insulin sensitivity. This condition contributes to bone demineralization and may be linked to altered serum levels of insulin and osteocalcin (OC), particularly when compounded by insufficient daily consumption of Vitamins D3 (VD3) and K2 (VK2). Osteocalcin is a 49 amino acid peptide synthesized in osteoblasts, existing primarily in fully carboxylated (cOC) and undercarboxylated (uOC) forms. The uOC form has been shown to have metabolic effects, stimulating insulin synthesis and secretion in pancreatic beta cells and improving glucose metabolism. VK2 is vital for the gamma-carboxylation of OC, promoting the integration of calcium into the bone. VD3 administration aids in the absorption and reabsorption of calcium, which is necessary for bone health. The study’s objective was to assess the impact of VD3 and VK2 supplements, individually or combined, on OC levels and metabolic parameters in patients with T2DM.
Methods and Study Design
A 3-month, double-blind, randomized clinical trial was conducted involving 40 patients with pre-existing T2DM diagnosis, ranging from 30 to 70 years of age. The patients were randomized into three intervention groups:
- Vitamin D3 Group (D): 1000 IU VD3 + calcined magnesium placebo (n=16).
- Vitamin K2 Group (K): 100 µg VK2 + calcined magnesium placebo (n=12).
- Combined Group (D + K): 1000 IU VD3 + 100 µg VK2 (n=12). The average time since T2DM diagnosis for the total population was 10.4 ± 4.8 years, and 85% of patients used Metformin as treatment. Outcomes measured included glucose, insulin, HOMA-IR (Homeostatic Model Assessment–Insulin Resistance), percentage of functional pancreatic beta cells (%FPβC), and the two forms of osteocalcin (uOC and cOC).
Key Results
After the 3-month treatment across the total studied population, significant improvements were observed, including a decrease in glycemia (p=0.001), HOMA-IR (p=0.040), % FPβC (p<0.001), and the uOC/cOC index (p=0.001). Diastolic blood pressure also significantly decreased (p=0.030). The concentration of cOC significantly increased in the total population (p=0.004).
Analysis of individual groups showed specific effects:
- VD3 Group: Demonstrated significant decreases in uOC (p=0.026), glucose (p<0.001), % FPβC (p<0.001), and the uOC/cOC index (p=0.039).
- VK2 Group: Showed significant decreases in glycemia (p=0.002), HOMA-IR (p=0.041), and % FPβC (p=0.002). cOC concentration significantly increased (p=0.041).
- D3 + K2 Group: Experienced significant decreases in glycemia (p=0.002), % FPβC (p=0.004), and the uOC/cOC index (p=0.023).
Conclusion
The study concluded that both individual and combined supplementation with vitamins D3 and K2 significantly decreased glucose levels and the percentage of functional pancreatic beta cells. The VD3 and D3 + K2 treatments also induced a reduction in the uOC/cOC index. A reduction in undercarboxylated osteocalcin was observed only in the VD3 group, while VK2 specifically increased carboxylated osteocalcin levels. These findings suggest that the therapeutic use of VD3, alone or in combination with VK2, could be a valuable adjunctive strategy for simultaneously improving glucose homeostasis and bone health in T2DM patients.
References
Aguayo-Ruiz, J. I., García-Cobián, T. A., Pascoe-González, S., Sánchez-Enríquez, S., Llamas-Covarrubias, I. M., García-Iglesias, T., López-Quintero, A., Llamas-Covarrubias, M. A., Trujillo-Quiroz, J., & Rivera-Leon, E. A. (2020). Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: A randomized, double-blind, clinical trial. Diabetology & Metabolic Syndrome, 12, 73. https://doi.org/10.1186/s13098-020-00580-w
This post is based on Open Access research and is for informational purposes only.
