Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients

Published:March 01, 2013DOI:https://doi.org/10.1016/j.clnu.2013.01.020

      Summary

      Background & aims

      Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients. The present study was designed to evaluate long term impact of high doses of vitamin D on arterial properties, glucose homeostasis, adiponectin and leptin in patients with type 2 diabetes mellitus.

      Methods and results

      In randomized, placebo-controlled study 47 diabetic patients were assigned into two groups: Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months. Group 2 received matching placebo capsules. Blood sampling for metabolic parameters, including fasting glucose, lipid profile, HbA1C, insulin, hs-CRP, 25 OH Vit D, adiponectin and leptin was performed at baseline and at the end of the study. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR). Central aortic augmentation index (AI) was evaluated using SphygmoCor.

      Results

      The two groups were similar at baseline in terms of hemodynamic parameters. After 12 months, AI decreased significantly during the treatment period in patients received vitamin D (p < 0.0001) and did not change in placebo group. Glucose homeostasis parameters, leptin as well as leptin adiponectin ratio did not change in both groups. 25 OH Vit D level significantly increased (p = 0.022) and circulating adiponectin marginally increased (p = 0.065) during 12 month treatment period in active treatment and did not change in placebo group.

      Conclusions

      High doses of vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment. This beneficial vascular effect was not associated with improvement in glucose homeostasis parameters.

      Keywords

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      References

        • 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
        • Need A.G.
        • O'Loughlin P.D.
        • Horowitz M.
        • Nordin B.
        Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women.
        Clin Endocrinol (Oxf). 2005; 62: 738-741
        • Palomer X.
        • González-Clemente J.M.
        • Blanco-Vaca F.
        • Mauricio D.
        Role of vitamin D in the pathogenesis of type 2 diabetes mellitus.
        Diabetes Obes Metab. 2008; 10: 185-197
        • Borissova A.M.
        • Tankova T.
        • Kirilov G.
        • Dakovska L.
        • Kovacheva R.
        The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients.
        Int J Clin Pract. 2003; 57: 258-261
        • Chiu K.C.
        • Chu A.
        • Go V.L.
        • Saad M.F.
        Hypovitaminosis D is associated with insulin resistance and ß-cell dysfunction.
        Am J Clin Nutr. 2004; 79: 820-825
        • Maestro B.
        • Campion J.
        • Davila N.
        • Calle C.
        Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells.
        Endocr J. 2000; 47: 383-391
        • Forman J.P.
        • Giovannucci E.
        • Holmes M.D.
        • Bischoff-Ferrari H.A.
        • Tworoger S.S.
        • Willett W.C.
        • et al.
        Plasma 25-hydroxyvitamin D levels and risk of incident hypertension.
        Hypertension. 2007; 49: 1063-1069
        • Zittermann A.
        Vitamin D and disease prevention with special reference to cardiovascular disease.
        Prog Biophys Mol Biol. 2006; 92: 39-48
        • Wang T.J.
        • Pencina M.J.
        • Booth S.L.
        • Jacques P.F.
        • Ingelsson E.
        • Lanier K.
        • et al.
        Vitamin D deficiency and risk of cardiovascular disease.
        Circulation. 2008; 117: 503-511
        • Giovannucci E.
        • Liu Y.
        • Hollis B.W.
        • Rimm E.B.
        25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study.
        Arch Intern Med. 2008; 168: 1174-1180
        • Al Mheid I.
        • Patel R.
        • Murrow J.
        • Morris A.
        • Rahman A.
        • Fike L.
        • et al.
        Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans.
        J Am Coll Cardiol. 2011; 58: 186-192
        • Harris R.A.
        • Pedersen-White J.
        • Guo D.H.
        • Stallmann-Jorgensen I.S.
        • Keeton D.
        • Huang Y.
        • et al.
        Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults.
        Am J Hypertens. 2011; 24: 557-562
        • Sugden J.A.
        • Davies J.I.
        • Witham M.D.
        • Morris A.D.
        • Struthers A.D.
        Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels.
        Diabet Med. 2008; 25: 320-325
        • van Popele N.M.
        • Grobbee D.E.
        • Bots M.L.
        • Asmar R.
        • Topouchian J.
        • Reneman R.S.
        • et al.
        Association between arterial stiffness and atherosclerosis: the Rotterdam study.
        Stroke. 2001; 32: 454-460
        • Cruickshank K.
        • Riste L.
        • Anderson S.G.
        • Wright J.S.
        • Dunn G.
        • Gosling R.G.
        Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance. An integrated index of vascular function?.
        Circulation. 2002; 106: 2085-2090
        • Zieman S.J.
        • Melenovsky V.
        • Kass D.A.
        Mechanisms, pathophysiology, and therapy of arterial stiffness.
        Arterioscler Thromb Vasc Biol. 2005; 25: 932-943
        • Schiffrin E.L.
        Vascular stiffening and arterial compliance.
        Am J Hypertens. 2004; 17: 39-48
        • Wan Y.
        • Heneghan C.
        • Stevens R.
        • McManus R.J.
        • Ward A.
        • Perera R.
        • et al.
        Determining which automatic digital blood pressure device performs adequately: a systematic review.
        J Hum Hypertens. 2010; 24: 431-438
        • O'Rourke M.
        • Staessen J.A.
        Clinical application of arterial stiffness definitions and reference values.
        Am J Hypertens. 2002; 15: 426-444
        • Giovannucci Edward
        • Liu Yan
        • Hollis Bruce W.
        • Rimm Eric B.
        ScD 25-hydroxyvitamin D and risk of myocardial infarction in men. A prospective study.
        Arch Intern Med. 2008; 168: 1174-1180
        • Mathieu C.
        • Waer M.
        • Laureys J.
        • Rutgeerts O.
        • Bouillon R.
        Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3.
        Diabetologia. 1994; 37: 552-558
        • Gregori S.
        • Giarratana N.
        • Smiroldo S.
        • Uskokovic M.
        • Adorini L.A.
        1alpha,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice.
        Diabetes. 2002; 51: 1367-1374
        • Pilz S.
        • van den Hurk K.
        • Nijpels G.
        • Stehouwer C.D.
        • Van't Riet E.
        • Kienreich K.
        • et al.
        Vitamin D status, incident diabetes and prospective changes in glucose metabolism in older subjects: the Hoorn study.
        Nutr Metab Cardiovasc Dis. 2012; 22: 883-889
        • Pittas A.G.
        • Harris S.S.
        • Stark P.C.
        • Dawson-Hughes B.
        The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in non-diabetic adults.
        Diabetes Care. 2007; 30: 980-986
        • Gepner A.D.
        • Ramamurthy R.
        • Krueger D.C.
        • Korcarz C.E.
        • Binkley N.
        • Stein J.H.
        A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk.
        PLoS One. 2012; 7: e36617
        • Larsen T.
        • Mose F.H.
        • Bech J.N.
        • Hansen A.B.
        • Pedersen E.B.
        Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial.
        Am J Hypertens. 2012; 25: 1215-1222
        • Orwoll E.
        • Riddle M.
        • Prince M.
        Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus.
        Am J Clin Nutr. 1994; 59: 1083-1087
        • Ljunghall S.
        • Lind L.
        • Lithell H.
        • Skarfors E.
        • Selinus I.
        • Sorensen O.H.
        • et al.
        Treatment with one-hydroxycholecalciferol in middle-aged men with impaired glucose tolerance – a prospective randomized double-blind study.
        Acta Med Scand. 1987; 222: 361-367
        • Stefan N.
        • Vozarova B.
        • Funahashi T.
        • Matsuzawa Y.
        • Weyer C.
        • Lindsay R.S.
        • et al.
        Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans.
        Diabetes. 2002; 51: 1884-1888
        • Tan K.C.B.
        • Xu A.
        • Chow W.S.
        • Lam M.C.W.
        • Ai V.H.G.
        • Tam S.C.F.
        • et al.
        Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation.
        J Clin Endocrinol Metab. 2004; 89: 765-769
        • Störk S.
        • Bots M.L.
        • Angerer P.
        • Schacky C.
        • Grobbee D.E.
        • Angermann C.E.
        • et al.
        Low levels of adiponectin predict worsening of arterial morphology and function.
        Atherosclerosis. 2007; 194: e147-e153
        • Ukkola O.
        • Santaniemi M.
        Adiponectin: a link between excess adiposity and associated comorbidities?.
        J Mol Med. 2002; 80: 696-702
        • Shargorodsky M.
        • Boaz M.
        • Goldberg Y.
        • Matas Z.
        • Gavish D.
        • Fux A.
        • et al.
        Adiponectin and vascular properties in obese patients: is it a novel biomarker of early atherosclerosis?.
        Int J Obes (Lond). 2009; 33: 553-558