Vitamin D, sub-inflammation and insulin resistance. A window on a potential role for the interaction between bone and glucose metabolism

Abstract

Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and recently it has been implicated in the pathogenesis of sub-inflammation, insulin resistance and obesity. The two main forms of vitamin D are cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2): the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Vitamin D increases the production of some anti-inflammatory cytokines and reduces the release of some pro-inflammatory cytokines. Low levels of Vitamin D are also associated with an up-regulation of TLRs expression and a pro-inflammatory state. Regardless of the effect on inflammation, Vitamin D seems to directly increase insulin sensitivity and secretion, through different mechanisms. Considering the importance of low grade chronic inflammation in metabolic syndrome, obesity and diabetes, many authors hypothesized the involvement of this nutrient/hormone in the pathogenesis of these diseases. Vitamin D status could alter the balance between pro and anti-inflammatory cytokines and thus affect insulin action, lipid metabolism and adipose tissue function and structure. Numerous studies have shown that Vitamin D concentrations are inversely associated with pro-inflammatory markers, insulin resistance, glucose intolerance and obesity. Interestingly, some longitudinal trials suggested also an inverse association between vitamin D status and incident type 2 diabetes mellitus. However, vitamin D supplementation in humans showed controversial effects: with some studies demonstrating improvements in insulin sensitivity, glucose and lipid metabolism while others showing no beneficial effect on glycemic control and on inflammation. In conclusion, although the evidences of a significant role of Vitamin D on inflammation, insulin resistance and insulin secretion in the pathogenesis of obesity, metabolic syndrome and type 2 diabetes, its potential function in treatment and prevention of type 2 diabetes mellitus is unclear. Encouraging results have emerged from Vitamin D supplementation trials on patients at risk of developing diabetes and further studies are needed to fully explore and understand its clinical applications.

Vitamin D deficiency and insulin resistance

“…Celulele β-pancreatice suferă modificări, conducând la eliberarea unor cantități mari de insulină, hiperinsulinemia instalată va determina apariția DZ2 în procent de 60% [18][19][20]. Rezistența la insulină este strâns corelată cu obezitatea, care, la rândul ei, este asociată cu stresul oxidativ și un nivel inflamator crescut [18,21]. Deficiența de vitamină D poate fi implicată în patogeneza dezechilibrelor metabolice care determină instalarea hiperglicemiei și a obezității [22].…”

Association of VDR gene variant (rs1544410) with type 2 diabetes in a Pakistani cohort

“…Recent studies have shown that high vitamin D status offers protection against T2DM. Vitamin D has important biological functions including modifying insulin secretion and refining insulin resistance [3]. It is a hormone precursor and it has been found to be associated with various metabolic disorders [4].…”

Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.

“…Preliminary findings have suggested that vitamin D supplementation may improve cognition in schizophrenia , however the association of hypovitaminosis D with cognitive impairment has not been explored to date. Vitamin D insufficiency has been associated with metabolic syndrome in psychotic disorders (Yoo et al, 2018), with insulin resistance (Garbossa and Folli, 2017), with thyroid dysfunction (Kim, 2017;Wang et al, 2018) and high vitamin D blood levels have been suggested to reduce peripheral low-grade inflammation (Zhu et al, 2015). There is a current debate on the association between alcohol use disorder and vitamin D deficiency (Tardelli et al, 2017).…”