To the Editor: Inflammation, with excessive production of matrix metalloproteinase (MMP)-9 in unstable plaque, has a major role in the progression of macrovascular disease, including the development of acute events [1]. In a recent issue of Diabetologia, Toni et al [2] report increased circulating MMP-10 in association with increased microvascular disease risks in type 1 diabetes; this finding is in line with the earlier observations, and, as the authors suggest, provides a potential therapeutic target for reducing microvascular disease risks. Vitamin D repletion is associated with reductions in macrovascular disease risks and, although causation remains unproven, plausible mechanisms exist [3]. Increased circulating MMP-9, inversely correlated with severity of vitamin D insufficiency, was reduced by ∼70% in response to modest improvement in vitamin D repletion in healthy South Asians [4], and circulating MMP-9 increased with reduction in vitamin D status in submariners after an 85 day submerged patrol [5]. Furthermore, MMP-10 formation, increased in peripheral blood mononuclear cells by exposure to Mycobacterium tuberculosis, was inhibited by activated vitamin D [6]. It would, therefore, be useful if Toni and colleagues could examine serum 25-hydroxyvitamin D concentrations in the participants in this study as a potential independent predictor for MMP-10 and microvascular complications, since lower vitamin D status has been found to be associated with increases in the prevalence of both diabetic retinopathy and diabetic nephropathy in a study of patients with type 2 diabetes [7]. If there is such an association, then the potential for reduction in circulating MMP-10 by correction of vitamin D deficiency should be examined early in the search for pharmacological agents to lower MMP-10 production in diabetes, since modest vitamin D supplementation might prove to be a particularly cost-effective way of reducing the problems of diabetic complications.
Abbreviations
- MMP:
-
Matrix metalloproteinase
References
Beaudeux JL, Giral P, Bruckert E, Foglietti MJ et al (2004) Matrix metalloproteinases, inflammation and atherosclerosis: therapeutic perspectives. Clin Chem Lab Med 42:121–131
Toni M, Hermida J, Goni MJ, Fernandez P et al (2013) Matrix metalloproteinase-10 plays an active role in microvascular complications in type 1 diabetic patients. Diabetologia 56:2743–2752
Norman PE, Powell JT (2014) Vitamin D and cardiovascular disease. Circ Res 114:379–393
Timms PM, Mannan N, Hitman GA, Noonan K et al (2002) Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? Q J Med 95:787–796
Baker A, Wood CL, Wood AM, Timms PM et al (2014) Changes in vitamin D and matrix metalloproteinase-9 in submariners during a submerged patrol. Occup Environ Med 71:104–108
Coussens AK, Timms PM, Boucher BJ, Venton AT et al (2009) 1α,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection. Immunology 127:539–548
Ahmadieh H, Azar ST, Lakkis N, Arabi A (2013) Hypovitaminosis D in patients with type 2 diabetes mellitus: a relation to disease control and complications. ISTN Endocrinol doi:10.1155/2013/641098
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Boucher, B.J. Matrix metalloproteinase-10 and microvascular complications of type 1 diabetes: might vitamin D status be relevant?. Diabetologia 57, 1081 (2014). https://doi.org/10.1007/s00125-014-3189-9
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DOI: https://doi.org/10.1007/s00125-014-3189-9