Vitamin D is known to have positive impacts on those diagnosed with Type 2 Diabetes Mellitus.
A Little Background About Type 2 Diabetes Mellitus
According to the World Health Organization, Type 2 Diabetes Mellitus (T2DM) accounts for 90% of diabetes cases globally, with 15 million individuals suffering from the condition worldwide (Szymczak-Pajor and Ślinwińska, 2019). T2DM is a condition where either damage to pancreatic beta cells making them unable to secrete insulin or, cells in the body do not respond to insulin, stopping sugar or glucose from being transported from the blood and into the cells. Major symptoms of T2DM are excessive thirst (polydipsia), excessive urination (polyuria), increased appetite, and unintentional weight loss. Significant risk factors for developing this condition are obesity, diet, and physical inactivity, though genetic risk factors exist too. One complication of T2DM is advanced glycation end products (AGEs), where substances that would not normally pass through blood vessels, are more likely to pass through. Accumulation of AGEs are known to contribute to kidney disease associated with diabetes by disturbing calcium balance, introducing oxidative stress and inflammatory responses. (Huang et al., 2019). Another complication is decreased elasticity of blood vessels which increases the stiffness of the vessels. Stiffening of vessels also occurs in conditions such as hypertension or high blood pressure. T2DM can reduce the ability to clear lipoproteins from the blood, increasing the risk of developing conditions such as atherosclerosis. It can also change the way enzymes function. If T2DM goes untreated, it can lead to disease of the retina of the eye (retinopathy), potentially leading to blindness. A person may also experience numbness, burning, or prickling/tingling sensations in the fingers and toes, end-stage kidney disease (nephropathy), foot infections leading to amputations, and coronary heart disease.
The inability of cells to respond to insulin is a process called insulin resistance. Insulin is a hormone that is largely responsible for controlling carbohydrates, lipids or fat, and energy metabolism. It helps store glucose in skeletal muscles and the liver, insulin begins the utilization of glucose in skeletal muscles, and it supports gene regulation (Rafiq and Jeppesen, 2021). Insulin can also suppress the breakdown of lipids or fats in the liver, thus decreasing the activity of pyruvate carboxylase, and decreasing this activity and glycerol production helps insulin reduce the creation of sugar (Rafiq and Jeppesen, 2021). Insulin resistance occurs when insulin is constantly released, causing damage to beta cells. This damage causes insufficient insulin secretion. Insulin is needed to bring the sugar from the blood into the cells. So, insulin secretion dysfunction can lead to high sugar in the blood or hyperglycemia. Factors contributing to developing insulin resistance and T2DM are systemic inflammation, errors in the insulin signaling pathway, and pancreatic-beta cell dysfunction (Szymczak-Pajor and Ślinwińska, 2019).A Little
Those with T2DM commonly experience, decreased in pancreatic beta cell function, decreased insulin sensitivity, changes in calcium release and retention/ fluxes, chronic inflammation, and calbindin regulation (Contreras-Bolívar, 2021). Calbindin-D28k is responsible for regulating calcium levels in the kidneys by allowing for transportation and regulation of calcium levels in the cells. (Huang et al., 2019).
Background on Vitamin D
Vitamin D is a fat-soluble vitamin that comes in two forms, vitamin D2, found in plants like shitake mushrooms, and vitamin D3, from cheese and animal sources such as salmon and fatty fish. Vitamin D2 is the inactive form that metabolizes in the liver, and vitamin D3 is the active form that metabolizes in the kidneys. When vitamin D levels are low in the blood, vitamin D2 can convert to D3 more efficiently. Vitamin D balances calcium levels, with the help of parathyroid hormones, and affects phosphorous levels, indirectly playing a role in bone metabolism.
Vitamin D deficiency presents when impaired absorption, increased catabolism, increased loss of vitamin D2 through urine, and vitamin D transport dysfunction occur (Szymczak-Pajor et al., 2020). Lifestyle factors also contributing to vitamin D deficiency include using sunscreens or sun oils, an individual's diet, breastfeeding, and increased time spent indoors (Szymczak-Pajor et al., 2020). Obesity-causing diets can put an individual at a higher risk for vitamin D deficiency because body fat makes vitamin D less available for physiological reactions (Dominguez et al., 2021). People at risk for developing vitamin D deficiency include the infant and elderly populations, those with parathyroid gland, liver, or kidney disorders, and individuals taking anticonvulsant medications (Gropper et al., 2022). Medications known to increase liver enzyme activity contribute to vitamin D deficiency because increased enzyme activity also increases the speed at which vitamin D is broken down (Dominguez et al., 2021). Szymczak-Pajor et al., (2020) cited a study by Carmo et al. finding potential toxicity associated with high doses of Vitamin D. Too much Vitamin D can lead to a condition called hypercalcemia, meaning there is excess calcium in the blood (Szymczak-Pajor et al., 2020). Hypercalcemia can lead to the development of depression, kidney stones, bone pain, constipation, abnormal heart rhythm, and many other conditions if not treated (Sadiq et al., 2022).
Vitamin D and Type 2 Diabetes Melltus
Ojo (2019) found vitamin D deficiency to be a risk factor for developing T2DM because vitamin D affects insulin secretion, insulin resistance, and systemic inflammation. Again, those with T2DM commonly undergo decreased pancreatic beta cell function and reduced insulin sensitivity (Contreras-Bolívar, 2021). They will also experience changes in calcium release and retention, chronic inflammation, and changes in calbindin regulation (Contreras-Bolívar, 2021). Calbindin-D28k regulates calcium levels in the kidneys by allowing for its transport and control. (Huang et al., 2019). As a chemical messenger, vitamin D can affect calcium-flux regulation receptors on beta-cells (Contreras-Bolívar, 2021), allowing vitamin D to control calcium levels in those cells. Vitamin D is presumed to be involved in controlling insulin transcription because of the promoter insulin receptor gene contained within it (Contreras-Bolívar, 2021). It can increase the number of insulin receptors, activating peroxisome proliferator-activated receptor delta (PPAR-delta) to improve insulin sensitivity (Contreras-Bolívar, 2021). Improving insulin sensitivity allows cells to become more responsive to insulin so that glucose can be transported from the blood and into the cells, decreasing the chances of hyperglycemia. Vitamin D can potentially reduce chronic inflammation by inactivating inflammatory cytokines related to insulin resistance (Contreras-Bolívar, 2021). It also protects cells from apoptosis, or cell death, by promoting calbindin expression (Contreras-Bolívar, 2021).
A deficiency in vitamin D may make it challenging for beta cells to convert proinsulin to insulin (Contreras-Bolívar, 2021). Szymczak-Pajor and Ślinwińska (2019) express available evidence showing vitamin D’s role in aiding the release of insulin from pancreatic beta cells. Overactivity from the renin-angiotensin-aldosterone system (RAAS), the system responsible for regulating blood pressure and balancing electrolytes and fluids, is a suggested cause of beta cell dysfunction (Contreras-Bolívar, 2021). The RAAS is known to stop the actions of insulin in peripheral tissues and control the amount of calcium in skeletal muscles (Szymczak-Pajor et al., 2020). Contreras-Bolívar (2021) mentioned proof showing that vitamin D may reduce RAAS activity, thus improving the function of beta cells (Contreras-Bolívar, 2021). Improvement of beta cells means potential improvement in insulin secretion. Vitamin D may also potentially improve insulin sensitivity because if RAAS makes cells resistant to insulin, and vitamin D potentially decreases the activity of the system, then vitamin D may reduce insulin resistance induced by RAAS.
Overall, T2DM is a condition that affects individuals globally and occurs when either glucose in the blood does not respond to insulin or dysfunction of the beta cells makes it challenging to release insulin. Vitamin D is a fat-soluble vitamin that regulates calcium and phosphorus levels. It is known to assist in the regulation of insulin and plays a role in reducing systemic inflammation. Vitamin D can also potentially affect the RAAS to improve the function of beta cells, thus possibly improving insulin secretion and resistance. Vitamin D may be considered in treating T2DM because of its effects on insulin sensitivity and chronic inflammation and its possible impact on beta cell functioning. All of which are factors associated with the development of this condition. Future studies should further evaluate vitamin D's effect on beta cells.
References:
Contreras- Bolívar, V., García-Fontana, B., García-Fontana, C., Muñoz-Torres, M. (2021). Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice. Nutrients. 13(3491). 1-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539968/pdf/nutrients-13-03491.pdf
Dominguez, L.J., Farruggia, M., Veronese, N., Barbagallo, M. (2021). Vitamin D Sources, Metabolism, and Deficiency: Available Compounds and Guidelines for Its Treatment. Metabolites. 11(255). 1-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074587/pdf/metabolites-11-00255.pdf
Gropper, S.S., Smith, J.L., Carr, T.P. ().Advanced Nutrition and Human Metabolism. Cengage. 423-435.
Huang, K-H., Guan, S-S., Lin, W-H., Wu, C-T., Sheu, M-L., Chiang, C-K., Liu, S-H. (2019). Role of Calbindin-D28k in Diabetes-Associated Advanced Glycation End-Products-Induced Renal Proximal Tubule Cell Injury. Cells. 8(660). 1-17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678974/pdf/cells-08-00660.pdf
Ojo, O. (2019). Dietary Intake and Type 2 Diabetes. Nutrients. 11(2177). 1-6.
Rafiq, S., Jeppesen, P.B. (2021). Insulin Resistance Is Inversely Associated with the Status of Vitamin D in Both Diabetic and Non-Diabetic Populations. Nutrients. 13(1742). 1-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224049/pdf/nutrients-13-01742.pdf
Sadiq, N.M., Naganathan, S., Badireddy, M. (2022). Hypercalcemia. StatsPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK430714/
Szymczak-Pajor, I., Drzewoski, J., Ślinwińska, A. (2020). The Molecular Mechanisms by Which Vitamin D Prevents Insulin Resistance and Associated Disorders. Int. J. Mol. Sci. 21(6644). 1-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554927/pdf/ijms-21-06644.pdf
Szymczak-Pajor, I., Ślinwińska, A. (2019). Analysis of Association between Vitamin D Deficiency and Insulin Resistance. Nutrients. 11(794). 1-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520736/pdf/nutrients-11-00794.pdf
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