The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes

  • Ryu, Ohk-Hyun (Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University College of Medicine) ;
  • Chung, Wankyo (Department of Healthcare Management, Hallym University School of Business) ;
  • Lee, Sungwha (Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University College of Medicine) ;
  • Hong, Kyung-Soon (Division of Cardiology, Department of Internal Medicine, Hallym University College of Medicine) ;
  • Choi, Moon-Gi (Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University College of Medicine) ;
  • Yoo, Hyung Joon (Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University College of Medicine)
  • Received : 2013.10.25
  • Accepted : 2013.12.30
  • Published : 2014.09.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels, glucose intolerance/insulin resistance (IR), and cardiovascular disease. However, few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk, such as IR and arterial stiffness, in diabetes. We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients, including metabolic parameters, IR, and arterial stiffness. Methods: We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes. We excluded patients who were taking vitamin D or calcium supplements. We randomized participants into the vitamin D group (cholecalciferol 2,000 IU/day + calcium 200 mg/day, n = 40) or the placebo group (calcium 200 mg/day, n = 41). We compared their IR (homeostasis model of assessment [HOMA]-IR) and arterial stiffness (brachial-ankle pulse wave velocity and radial augmentation index) before and after 24 weeks of intervention. Results: The baseline characteristics of the two groups were similar. A total of 62 participants (placebo, 30; vitamin D, 32) completed the study protocol. At the end of the study period, the 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in the vitamin D group than in the placebo group ($35.4{\pm}8.5ng/mL$ vs. $18.4{\pm}7.3ng/mL$, p < 0.001). There was no difference in HOMA-IR or changes in arterial stiffness (placebo, 21, vitamin D, 24) between the groups. Conclusions: Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels. However, we identified no beneficial effects on cardiovascular risk in type 2 diabetes, including IR and arterial stiffness.

Keywords

References

  1. Karnchanasorn R, Ou HY, Chiu KC. Plasma 25-hydroxyvitamin D levels are favorably associated with beta-cell function. Pancreas 2012;41:863-868. https://doi.org/10.1097/MPA.0b013e31823c947c
  2. Shankar A, Sabanayagam C, Kalidindi S. Serum 25-hydroxyvitamin d levels and prediabetes among subjects free of diabetes. Diabetes Care 2011;34:1114-1119. https://doi.org/10.2337/dc10-1203
  3. Chitalia N, Recio-Mayoral A, Kaski JC, Banerjee D. Vitamin D deficiency and endothelial dysfunction in non-dialysis chronic kidney disease patients. Atherosclerosis 2012;220:265-268. https://doi.org/10.1016/j.atherosclerosis.2011.10.023
  4. Ertek S, Akgul E, Cicero AF, et al. 25-Hydroxy vitamin D levels and endothelial vasodilator function in normotensive women. Arch Med Sci 2012;8:47-52.
  5. Anderson JL, May HT, Horne BD, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010;106:963-968. https://doi.org/10.1016/j.amjcard.2010.05.027
  6. Karakas M, Thorand B, Zierer A, et al. Low levels of serum 25-hydroxyvitamin D are associated with increased risk of myocardial infarction, especially in women: results from the MONICA/KORA Augsburg case-cohort study. J Clin Endocrinol Metab 2013;98:272-280. https://doi.org/10.1210/jc.2012-2368
  7. Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol 2012;109:359-363. https://doi.org/10.1016/j.amjcard.2011.09.020
  8. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503-511. https://doi.org/10.1161/CIRCULATIONAHA.107.706127
  9. Choi HS, Oh HJ, Choi H, et al. Vitamin D insufficiency in Korea: a greater threat to younger generation: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008. J Clin Endocrinol Metab 2011;96:643-651. https://doi.org/10.1210/jc.2010-2133
  10. Dong Y, Pollock N, Stallmann-Jorgensen IS, et al. Low 25-hydroxyvitamin D levels in adolescents: race, sea-son, adiposity, physical activity, and fitness. Pediatrics 2010;125:1104-1111. https://doi.org/10.1542/peds.2009-2055
  11. Isaia G, Giorgino R, Adami S. High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 2001;24:1496.
  12. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004;79:820-825. https://doi.org/10.1093/ajcn/79.5.820
  13. Lee JI, Oh SJ, Ha WC, et al. Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes. Diabetes Res Clin Pract 2012;95:42-47. https://doi.org/10.1016/j.diabres.2011.09.006
  14. Giallauria F, Milaneschi Y, Tanaka T, et al. Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging. J Clin Endocrinol Metab 2012;97:3717-3723. https://doi.org/10.1210/jc.2012-1584
  15. Cigolini M, Iagulli MP, Miconi V, Galiotto M, Lombardi S, Targher G. Serum 25-hydroxyvitamin D3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care 2006;29:722-724. https://doi.org/10.2337/diacare.29.03.06.dc05-2148
  16. Joergensen C, Gall MA, Schmedes A, Tarnow L, Parving HH, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care 2010;33:2238-2243. https://doi.org/10.2337/dc10-0582
  17. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient: a randomised, placebo-controlled trial. Br J Nutr 2010;103:549-555. https://doi.org/10.1017/S0007114509992017
  18. Wood AD, Secombes KR, Thies F, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo- controlled RCT. J Clin Endocrinol Metab 2012;97:3557-3568. https://doi.org/10.1210/jc.2012-2126
  19. Davidson MB, Duran P, Lee ML, Friedman TC. Highdose vitamin D supplementation in people with prediabetes and hypovitaminosis D. Diabetes Care 2013;36:260-266. https://doi.org/10.2337/dc12-1204
  20. Dong Y, Stallmann-Jorgensen IS, Pollock NK, et al. A 16- week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. J Clin Endocrinol Metab 2010;95:4584-4591. https://doi.org/10.1210/jc.2010-0606
  21. Harris RA, Pedersen-White J, Guo DH, et al. Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. Am J Hypertens 2011;24:557-562. https://doi.org/10.1038/ajh.2011.12
  22. Tarcin O, Yavuz DG, Ozben B, et al. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 2009;94:4023-4030. https://doi.org/10.1210/jc.2008-1212
  23. Witham MD, Price RJ, Struthers AD, et al. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. JAMA Intern Med 2013;173:1672-1679.
  24. Yiu YF, Yiu KH, Siu CW, et al. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Atherosclerosis 2013;227:140- https://doi.org/10.1016/j.atherosclerosis.2012.12.013
  25. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003;77:204-210. https://doi.org/10.1093/ajcn/77.1.204
  26. Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: definition, prevalence, consequences, and correction. Endocrinol Metab Clin North Am 2010;39:287-301. https://doi.org/10.1016/j.ecl.2010.02.008
  27. Lee MY, Ryu OH, Choi MG. Seasonal variations of vitamin D levels in Korean type 2 diabetic patients. 61st Scientific Sessions of Korean Association of Internal Medicine; 2010 Oct 23; Seoul. Seoul: Korean Association of Internal Medicine, 2010: S390.
  28. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-1930. https://doi.org/10.1210/jc.2011-0385
  29. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-419. https://doi.org/10.1007/BF00280883
  30. Merke J, Hofmann W, Goldschmidt D, Ritz E. Demonstration of $1,25(OH)_{2}$ vitamin D3 receptors and actions in vascular smooth muscle cells in vitro. Calcif Tissue Int 1987;41:112-114. https://doi.org/10.1007/BF02555253
  31. Wong MS, Delansorne R, Man RY, Vanhoutte PM. Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 2008;295:H289-H296. https://doi.org/10.1152/ajpheart.00116.2008
  32. Nibbelink KA, Tishkoff DX, Hershey SD, Rahman A, Simpson RU. 1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte. J Steroid Biochem Mol Biol 2007;103:533-537. https://doi.org/10.1016/j.jsbmb.2006.12.099
  33. Forman JP, Williams JS, Fisher ND. Plasma 25-hydroxyvi tamin D and regulation of the renin-angiotensin system in humans. Hypertension 2010;55:1283-1288. https://doi.org/10.1161/HYPERTENSIONAHA.109.148619
  34. Tomaschitz A, Pilz S, Ritz E, et al. Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chim Acta 2010;411:1354-1360. https://doi.org/10.1016/j.cca.2010.05.037
  35. Riek AE, Oh J, Bernal-Mizrachi C. $1,25(OH)_{2}$ vitamin D suppresses macrophage migration and reverses atherogenic cholesterol metabolism in type 2 diabetic patients. J Steroid Biochem Mol Biol 2013;136:309-312. https://doi.org/10.1016/j.jsbmb.2012.12.019
  36. Oh J, Weng S, Felton SK, et al. $1,25(OH)_{2}$ vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation 2009;120:687-698. https://doi.org/10.1161/CIRCULATIONAHA.109.856070
  37. Sengstock DM, Vaitkevicius PV, Supiano MA. Arterial stiffness is related to insulin resistance in nondiabetic hypertensive older adults. J Clin Endocrinol Metab 2005;90:2823-2827. https://doi.org/10.1210/jc.2004-1686
  38. Tomiyama H, Hashimoto H, Hirayama Y, et al. Synergistic acceleration of arterial stiffening in the presence of raised blood pressure and raised plasma glucose. Hypertension 2006;47:180-188. https://doi.org/10.1161/01.HYP.0000198539.34501.1a
  39. Mansour AS, Yannoutsos A, Majahalme N, et al. Aortic stiffness and cardiovascular risk in type 2 diabetes. J Hypertens 2013;31:1584-1592. https://doi.org/10.1097/HJH.0b013e3283613074
  40. Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J 2003;17:509-511. https://doi.org/10.1096/fj.02-0424fje
  41. Longenecker CT, Hileman CO, Carman TL, et al. Vitamin D supplementation and endothelial function in vitamin D deficient HIV-infected patients: a randomized placebo- controlled trial. Antivir Ther 2012;17:613-621.
  42. Sokol SI, Srinivas V, Crandall JP, et al. The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vasc Med 2012;17:394-404. https://doi.org/10.1177/1358863X12466709
  43. Stricker H, Tosi Bianda F, Guidicelli-Nicolosi S, Limoni C, Colucci G. Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study. Eur J Vasc Endovasc Surg 2012;44:307-312. https://doi.org/10.1016/j.ejvs.2012.06.023
  44. Pirro M, Manfredelli MR, Helou RS, et al. Association of parathyroid hormone and 25-OH-vitamin D levels with arterial stiffness in postmenopausal women with vitamin D insufficiency. J Atheroscler Thromb 2012;19:924-931. https://doi.org/10.5551/jat.13128
  45. Aloia JF, Talwar SA, Pollack S, Feuerman M, Yeh JK. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women. Am J Clin Nutr 2006;84:602-609. https://doi.org/10.1093/ajcn/84.3.602
  46. Yki-Jarvinen H, Westerbacka J. Insulin resistance, arterial stiffness and wave reflection. Adv Cardiol 2007;44:252-260.
  47. Reid IR, Bolland MJ, Grey A. Does calcium supplementation increase cardiovascular risk? Clin Endocrinol (Oxf ) 2010;73:689-695. https://doi.org/10.1111/j.1365-2265.2010.03792.x

Cited by

  1. Is vitamin D supplementation really effective in patients with type 2 diabetes? vol.29, pp.5, 2014, https://doi.org/10.3904/kjim.2014.29.5.574
  2. Vitamin D Status and Response to Initial Vitamin D Supplementation in Korean Women with Osteoporosis vol.21, pp.4, 2014, https://doi.org/10.11005/jbm.2014.21.4.257
  3. The Role of Vitamin D in Diabetes and Cardiovascular Disease: An Updated Review of the Literature vol.2015, pp.None, 2014, https://doi.org/10.1155/2015/580474
  4. High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency vol.2015, pp.None, 2015, https://doi.org/10.1155/2015/918968
  5. Links between Vitamin D Deficiency and Cardiovascular Diseases vol.2015, pp.None, 2015, https://doi.org/10.1155/2015/109275
  6. Vitamin D deficiency and seasonal variation over the years in São Paulo, Brazil vol.27, pp.12, 2014, https://doi.org/10.1007/s00198-016-3670-z
  7. Hypovitaminosis D: a novel risk factor for coronary heart disease in type 2 diabetes? vol.51, pp.2, 2014, https://doi.org/10.1007/s12020-015-0609-7
  8. Prevalence of Vitamin D deficiency in Pakistan and implications for the future vol.9, pp.2, 2016, https://doi.org/10.1586/17512433.2016.1122519
  9. Effect of vitamin D supplementation on measures of arterial stiffness: a systematic review and meta‐analysis of randomized controlled trials vol.84, pp.5, 2016, https://doi.org/10.1111/cen.13031
  10. Effect of vitamin D supplementation on cardiovascular disease risk factors and exercise performance in healthy participants: a randomized placebo-controlled preliminary study vol.7, pp.4, 2016, https://doi.org/10.1177/2042018816653357
  11. The Effect of High Dose Cholecalciferol on Arterial Stiffness and Peripheral and Central Blood Pressure in Healthy Humans: A Randomized Controlled Trial vol.11, pp.8, 2014, https://doi.org/10.1371/journal.pone.0160905
  12. Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial vol.8, pp.1, 2014, https://doi.org/10.1007/s12672-016-0278-x
  13. Clinical and Metabolic Response to Vitamin D Supplementation in Endometrial Hyperplasia: a Randomized, Double-Blind, Placebo-Controlled Trial vol.8, pp.3, 2014, https://doi.org/10.1007/s12672-017-0290-9
  14. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness vol.2017, pp.None, 2014, https://doi.org/10.1155/2017/8784971
  15. Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD vol.12, pp.9, 2014, https://doi.org/10.2215/cjn.10791016
  16. Effect of Vitamin D Supplementation on Vascular Functions and Oxidative Stress in Type 2 Diabetic Patients with Vitamin D Deficiency vol.21, pp.4, 2014, https://doi.org/10.4103/ijem.ijem_140_17
  17. Effect of Monthly, High‐Dose, Long‐Term Vitamin D Supplementation on Central Blood Pressure Parameters: A Randomized Controlled Trial Substudy vol.6, pp.10, 2014, https://doi.org/10.1161/jaha.117.006802
  18. Noncalcemic adverse effects and withdrawals in randomized controlled trials of long-term vitamin D2 or D3 supplementation: a systematic review and meta-analysis vol.75, pp.12, 2014, https://doi.org/10.1093/nutrit/nux059
  19. Calcium and vitamin D3 combinations improve fatty liver disease through AMPK-independent mechanisms vol.57, pp.2, 2014, https://doi.org/10.1007/s00394-016-1360-4
  20. Vitamin D3-fortified milk did not affect glycemic control, lipid profile, and anthropometric measures in patients with type 2 diabetes, a triple-blind randomized clinical trial vol.72, pp.8, 2014, https://doi.org/10.1038/s41430-017-0062-1
  21. Vitamin D Supplementation, Serum 25(OH)D Concentrations and Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis vol.5, pp.None, 2014, https://doi.org/10.3389/fcvm.2018.00087
  22. Role of vitamin D in energy and bone metabolism in postmenopausal women with type 2 diabetes mellitus: A 6‐month follow‐up evaluation vol.9, pp.1, 2014, https://doi.org/10.1111/jdi.12666
  23. The Eeffect of Metformin Combined with Calcium-Vitamin D 3 Against Diet-Induced Nonalcoholic Fatty Liver Disease vol.8, pp.1, 2014, https://doi.org/10.15171/apb.2018.012
  24. The Effect of Vitamin D Supplementation on Glycemic Control in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis vol.10, pp.3, 2014, https://doi.org/10.3390/nu10030375
  25. 건강검진 수검자에서 혈청 Vitamin D 수준과 인슐린저항성 및 β-세포 기능과의 관련성 vol.43, pp.1, 2014, https://doi.org/10.5393/jamch.2018.43.1.018
  26. Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials vol.76, pp.5, 2014, https://doi.org/10.1093/nutrit/nux077
  27. Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta‐Analysis vol.7, pp.11, 2018, https://doi.org/10.1161/jaha.117.008273
  28. The effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo- vol.84, pp.1, 2014, https://doi.org/10.1016/j.pnpbp.2018.02.007
  29. Impaired Cardiac Functions and Aortic Elastic Properties in Patients with Severe Vitamin D Deficiency vol.28, pp.3, 2014, https://doi.org/10.4103/jcecho.jcecho_82_17
  30. Correlations between Vascular Stiffness Indicators, OPG, and 25-OH Vitamin D3 Status in Heart Failure Patients vol.55, pp.6, 2019, https://doi.org/10.3390/medicina55060309
  31. Effect of 9 months of vitamin D supplementation on arterial stiffness and blood pressure in Graves’ disease: a randomized clinical trial vol.66, pp.2, 2019, https://doi.org/10.1007/s12020-019-01997-8
  32. Effect of vitamin D supplementation on serum lipid profiles: a systematic review and meta-analysis vol.77, pp.12, 2014, https://doi.org/10.1093/nutrit/nuz037
  33. The impact of vitamin D supplementation on VDR gene expression and body composition in monozygotic twins: randomized controlled trial vol.10, pp.None, 2020, https://doi.org/10.1038/s41598-020-69128-2
  34. Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial vol.21, pp.None, 2014, https://doi.org/10.1186/s12875-020-1096-3
  35. Effect of vitamin D supplementation on glycose homeostasis and islet function in vitamin D deficient or insufficient diabetes and prediabetes: a systematic review and meta-analysis vol.69, pp.3, 2014, https://doi.org/10.3164/jcbn.20-165
  36. Effects of Vitamin D Supplementation on Cardiovascular and Glycemic Biomarkers vol.10, pp.10, 2014, https://doi.org/10.1161/jaha.120.017727
  37. No effect of vitamin D supplementation on metabolic parameters but on lipids in patients with type 2 diabetes and chronic kidney disease vol.91, pp.5, 2014, https://doi.org/10.1024/0300-9831/a000642