The interplay between vitamin D status, subclinical inflammation, and prediabetes

Abstract

Vitamin D's role extends beyond classical calcium and phosphate homeostasis to encompass a pivotal influence on immune modulation and metabolic health. The mechanisms by which vitamin D exerts these effects involve its conversion to hormonally active calcitriol, which binds intracellular vitamin D receptors, initiating various downstream cascades. In this review, we tease out the evidence showing the relationship between vitamin D deficiency and prediabetes within the context of subclinical inflammation, with a special focus on the novel monocyte-to-HDL ratio (MHR), a novel inflammatory marker reflecting subclinical inflammation. This was based on a thorough literature review using reputable databases covering the period from 1980 to 2024. In light of this, we discuss calcitriol's anti-inflammatory effects and consequently link vitamin D deficiency to both overt and subclinical inflammation. Additionally, the utility of several biomarkers, notably MHR, in investigating this association is also discussed. We further reviewed the role of vitamin D deficiency in precipitating prediabetes and type 2 diabetes mellitus (T2DM) via insulin resistance, decreased insulin synthesis and secretion, and subclinical inflammation. Taken together, this mini review highlights that vitamin D deficiency is significantly associated with subclinical inflammation, playing a critical role in the development of prediabetes and the progression to T2DM. Addressing vitamin D deficiency through appropriate interventions may serve as a preventative measure against the development of prediabetes and T2DM.

Keywords: Insulin resistance; Monocyte-to-high-density-lipoprotein ratio; Prediabetes; Subclinical inflammation; Type 2 diabetes mellitus; Vitamin D.

Fig. 1

Chemical structures of vitamin D₂, vitamin D₃, and metabolites produced mainly by liver 25-hydroxyvitamin D₃ and by kidney 1α,25-dihydroxyvitamin D₃ (source: https://pubchem.ncbi.nlm.gov/).

Fig. 2

Overview of vitamin D metabolism: UVB radiation converts 7-dehydrocholesterol in the skin to pre-vitamin D₃, which transforms into vitamin D₃ with heat. Once in the bloodstream, vitamin D binds to VDBP and is transported to the liver, where it undergoes hydroxylation. This process results in the formation of 25(OH)D, which is subsequently converted to the active metabolite, 1,25(OH)₂D in the kidney. The synthesis of 1,25(OH)₂D is influenced by PTH stimulation and is inhibited by high levels of calcium, phosphate, and 1,25(OH)₂D itself. Created with BioRender.com.

Fig. 3

3a: Vitamin D deficiency hampers insulin signalling pathway, decreases GLUT4 and IR expression, and diminishes calcitriol's anti-inflammatory effects, ultimately resulting in insulin resistance and subclinical inflammation. 3b: Vitamin D deficiency negatively affects insulin synthesis and secretion through a combination of genomic and nongenomic actions. Created with BioRender.com.