Vitamin D status is associated with skin autofluorescence in patients with type 2 diabetes mellitus: a preliminary report

Cardiovascular Diabetology

S Simsek¹  F Stam²  H van Wijland³  P Lips¹  R Agca²  Y H M Krul-Poel² 

[1] Department of Internal Medicine/Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands;Department of Internal Medicine, Medical Centre Alkmaar, Wilhelminalaan 12, Alkmaar, 1815 JD, The Netherlands;Department of General Practice, DIAZON, Alkmaar, The Netherlands

关键词: Vitamin D deficiency;    Vitamin D;    Advanced glycation endproducts;    Type 2 diabetes mellitus;   

Others  :  1219965
DOI  :  10.1186/s12933-015-0250-z

 received in 2015-02-13, accepted in 2015-06-30,  发布年份 2015

【 摘 要 】

Background

Skin autofluorescence is a non-invasive measurement of advanced glycation end products (AGE), which are suggested to be one of the major agents in the pathogenesis and progression of diabetes related cardiovascular complications. Recently, low vitamin D status has been linked to the progression of type 2 diabetes mellitus (T2DM) and cardiovascular disease. The aim of this study is to investigate the association between vitamin D status and skin autofluorescence in patients with T2DM.

Methods

In this preliminary report skin autofluorescence was measured non-invasively with an AGE-reader in 245 patients with T2DM treated with lifestyle advice, metformin and/or sulphonylurea-derivatives. All patients were randomly assigned to receive either vitamin D 50,000 IU/month or placebo for 6 months.

Results

Skin autofluorescence was significantly higher in patients with a serum 25(OH)D <50 nmol/l compared to patients with a serum 25(OH)D >75 nmol/l (2.81 versus 2.41; p < 0.001). Mean serum 25(OH)D was 60.3 ± 23.4 nmol/l and was independently associated with skin autofluorescence (β −0.006; p < 0.001). Mean vitamin D increased from 60.8 to 103.6 nmol/l in the intervention group, however no effect was seen on accumulation of skin AGEs after 6 months compared to placebo.

Conclusions

Vitamin D status is independently associated with skin auto fluorescence in patients with well-controlled T2DM. No effect was seen on the amount of skin AGEs after a short period of 6 months vitamin D supplementation. Further research with longer follow-up and measurement of circulating advanced glycation end products is needed to elucidate the causality of the association.

【 授权许可】

   
2015 Krul-Poel et al.

【 图 表 】

Figure1.

【 参考文献 】

• [1]Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001; 414:813-820.
• [2]Meerwaldt R, Lutgers HL, Links TP, Graaff R, Baynes JW, Gans RO et al.. Skin autofluorescence is a strong predictor of cardiac mortality in diabetes. Diabetes Care. 2007; 30:107-112.
• [3]Meerwaldt R, Links T, Zeebregts C, Tio R, Hillebrands JL, Smit A. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes. Cardiovasc Diabetol. 2008; 7:29. BioMed Central Full Text
• [4]Verzijl N, DeGroot J, Thorpe SR, Bank RA, Shaw JN, Lyons TJ et al.. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem. 2000; 275:39027-39031.
• [5]Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988; 318:1315-1321.
• [6]Ramasamy R, Yan SF, Schmidt AM. The diverse ligand repertoire of the receptor for advanced glycation endproducts and pathways to the complications of diabetes. Vascul Pharmacol. 2012; 57:160-167.
• [7]Lutgers HL, Graaff R, Links TP, Ubink-Veltmaat LJ, Bilo HJ, Gans RO et al.. Skin autofluorescence as a noninvasive marker of vascular damage in patients with type 2 diabetes. Diabetes Care. 2006; 29:2654-2659.
• [8]Genuth S, Sun W, Cleary P, Sell DR, Dahms W, Malone J et al.. Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. Diabetes. 2005; 54:3103-3111.
• [9]Gerrits EG, Lutgers HL, Kleefstra N, Graaff R, Groenier KH, Smit AJ et al.. Skin autofluorescence: a tool to identify type 2 diabetic patients at risk for developing microvascular complications. Diabetes Care. 2008; 31:517-521.
• [10]Lutgers HL, Gerrits EG, Graaff R, Links TP, Sluiter WJ, Gans RO et al.. Skin autofluorescence provides additional information to the UK Prospective Diabetes Study (UKPDS) risk score for the estimation of cardiovascular prognosis in type 2 diabetes mellitus. Diabetologia. 2009; 52:789-797.
• [11]Noordzij MJ, Mulder DJ, Oomen PH, Brouwer T, Jager J, Castro CM et al.. Skin autofluorescence and risk of micro- and macrovascular complications in patients with type 2 diabetes mellitus-a multi-centre study. Diabet Med. 2012; 29:1556-1561.
• [12]de Vos LC, Mulder DJ, Smit AJ, Dullaart RP, Kleefstra N, Lijfering WM et al.. Skin autofluorescence is associated with 5-year mortality and cardiovascular events in patients with peripheral artery disease. Arterioscler Thromb Vasc Biol. 2014; 34:933-938.
• [13]Hofmann B, Adam AC, Jacobs K, Riemer M, Erbs C, Bushnaq H et al.. Advanced glycation end product associated skin autofluorescence: a mirror of vascular function? Exp Gerontol. 2013; 48:38-44.
• [14]de Vos LC, Noordzij MJ, Mulder DJ, Smit AJ, Lutgers HL, Dullaart RP et al.. Skin autofluorescence as a measure of advanced glycation end products deposition is elevated in peripheral artery disease. Arterioscler Thromb Vasc Biol. 2013; 33:131-138.
• [15]Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr. 2011; 65:1005-1015.
• [16]Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014; 114:379-393.
• [17]Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007; 92:2017-2029.
• [18]Sciacqua A, Perticone M, Grillo N, Falbo T, Bencardino G, Angotti E et al.. Vitamin D and 1-h post-load plasma glucose in hypertensive patients. Cardiovasc Diabetol. 2014; 13:48. BioMed Central Full Text
• [19]Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey. Diabetes Care. 2004; 27:2813-2818.
• [20]Tahrani AA, Ball A, Shepherd L, Rahim A, Jones AF, Bates A. The prevalence of vitamin D abnormalities in South Asians with type 2 diabetes mellitus in the UK. Int J Clin Pract. 2010; 64:351-355.
• [21]Bellan M, Guzzaloni G, Rinaldi M, Merlotti E, Ferrari C, Tagliaferri A et al.. Altered glucose metabolism rather than naive type 2 diabetes mellitus (T2DM) is related to vitamin D status in severe obesity. Cardiovasc Diabetol. 2014; 13:57. BioMed Central Full Text
• [22]Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE et al.. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol. 2004; 89–90:121-125.
• [23]Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM et al.. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001; 86:888-894.
• [24]Alvarez JA, Ashraf A. Role of vitamin d in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol. 2010; 2010:351385.
• [25]Chagas CE, Borges MC, Martini LA, Rogero MM. Focus on vitamin D, inflammation and type 2 diabetes. Nutrients. 2012; 4:52-67.
• [26]Ferder M, Inserra F, Manucha W, Ferder L. The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system. Am J Physiol Cell Physiol. 2013; 304:C1027-C1039.
• [27]Hewison M. An update on vitamin D and human immunity. Clin Endocrinol (Oxf). 2012; 76:315-325.
• [28]Zitman-Gal T, Green J, Pasmanik-Chor M, Golan E, Bernheim J, Benchetrit S. Vitamin D manipulates miR-181c, miR-20b and miR-15a in human umbilical vein endothelial cells exposed to a diabetic-like environment. Cardiovasc Diabetol. 2014; 13:8. BioMed Central Full Text
• [29]Salum E, Kals J, Kampus P, Salum T, Zilmer K, Aunapuu M et al.. Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats. Diabetes Res Clin Pract. 2013; 100:243-249.
• [30]Lee TW, Kao YH, Lee TI, Chang CJ, Lien GS, Chen YJ. Calcitriol modulates receptor for advanced glycation end products (RAGE) in diabetic hearts. Int J Cardiol. 2014; 173:236-241.
• [31]Krul-Poel YHM, Westra S, ten Boekel E, ter Wee MM, van Schoor NM, van Wijland H et al.. Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes (SUNNY Trial): a randomized placebo-controlled trial. Diabetes Care. 2015.
• [32]Krul-Poel YH, Van WH, Stam F, Ten BE, Lips P, Simsek S. Study protocol: a randomised placebo-controlled clinical trial to study the effect of vitamin D supplementation on glycaemic control in type 2 Diabetes Mellitus SUNNY trial. BMC Endocr Disord. 2014; 14:59. BioMed Central Full Text
• [33]Meerwaldt R, Graaff R, Oomen PH, Links TP, Jager JJ, Alderson NL et al.. Simple non-invasive assessment of advanced glycation endproduct accumulation. Diabetologia. 2004; 47:1324-1330.
• [34]Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK et al.. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011; 96:53-58.
• [35]Gerrits EG, Lutgers HL, Kleefstra N, Groenier KH, Smit AJ, Gans RO et al.. Skin advanced glycation end product accumulation is poorly reflected by glycemic control in type 2 diabetic patients (ZODIAC-9). J Diabetes Sci Technol. 2008; 2:572-577.
• [36]Talmor Y, Golan E, Benchetrit S, Bernheim J, Klein O, Green J et al.. Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells. Am J Physiol Renal Physiol. 2008; 294:F1059-F1064.
• [37]Miyata T. Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis (“carbonyl stress”). Bull Mem Acad R Med Belg. 2002; 157:189-196.
• [38]Sturmer M, Sebekova K, Fazeli G, Bahner U, Stab F, Heidland A. 25-Hydroxyvitamin d and advanced glycation endproducts in healthy and hypertensive subjects: are there interactions? J Ren Nutr. 2015; 25:209-216.
• [39]Koetsier M, Lutgers HL, de Jonge C, Links TP, Smit AJ, Graaff R. Reference values of skin autofluorescence. Diabetes Technol Ther. 2010; 12:399-403.