Abstract
Type 2 diabetes mellitus (T2DM) has become a significant global health care problem and its reported incidence is increasing at an alarming rate. Despite the improvement in therapy and development of new drugs, treatment still remains insufficient especially due to the associated side effects of most available drugs. Efforts are continuing toward disease prevention and search for safer drugs. Conflicting evidence is associating low levels of vitamin D in the body to T2DM and as such studies have been conducted to test the effect of vitamin D levels on incidence of diabetes, diabetic control as well as diabetic complications.
Despite the conflicting evidence, vitamin D replacement seems to have some beneficial effect on the many aspects of diabetes: incidence, control and complications. Further long term and more convincing controlled trials are required in order to draw firmer conclusions on this beneficial role of vitamin D treatment on T2DM.
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International Diabetes Federation (2013) IDF Diabetes Atlas, 6th edn. International Diabetes Federation, Brussels, pp 32–49
Chagas CE, Borges MC, Martini LA, Rogero MM (2012) Focus on vitamin D, inflammation and type 2 diabetes. Forum Nutr 4:52–67
Campbell IT, Jarrett RJ, Keen H (1975) Diurnal and seasonal variation in oral glucose tolerance: studies in the Antarctic. Diabetologia 11:139–145
DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J ClinNutr 80(6Suppl):1689S–1696S
Tsiaras WG, Weinstoc MA (2011) Factors influencing vitamin D status. Acta Derm Venereol 91:115–124
Blum M, Dolnikowski G, Seyoum E, Harris SS, Booth SL, Peterson J, Saltzman E, Dawson-Hughes B (2008) Vitamin D(3) in fat tissue. Endocrine 33:90–94
Issa C, Azar S, Zantout M (2014) Vitamin D replacement and type 2 diabetes mellitus. Curr Diabetes Rev 10(5):7–16
Ross AC, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS et al (2011) Institute of medicine (US) committee to review dietary reference intakes for vitamin D and calcium. In: Ross AC, Taylor CL, Yaktine AL, Valle HBD (eds) Dietary reference intakes for calcium and vitamin D. National Academies Press (US), Washington, DC
Cantorna MT, Zhu Y, Froicu M et al (2004) Vitamin D status, 1,25 dihydroxyvitamin D3, and the immune system. Am J ClinNutr 80(6):1717S–1720S
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011) Endocrine society. J Clin Endocrinol Metab 96(7):1911–1930
Looker AC, Jhonson CL, Lacher DA, Pfeiffer CM, Schleicher RL, Sempos CT (2001 Mar) Vitamin D status: United states 2001–2006. NCHS Data Brief 59:1–8
Gilsanz V, Kremer A, Mo AO et al (2010) Vitamin D status and its relation to muscle mass and muscle fat in young women. J Clin Endocrinol Metab 95:1595–1601. [PubMed: 20164290]
Dunlop TW, Vaisanen S, Frank C et al (2005) The human peroxisome proliferator-activated receptor delta gene is a primary target of 1alpha,25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol 349:248–260. [PubMed: 15890193]
Maestro B, Campion J, Davila N et al (2000) Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J 47:383–391
Draznin B, Sussman K, Kao M et al (1987) The existence of an optimal range of cytosolic free calcium for insulin-stimulated glucose transport in rat adipocytes. J Biol Chem 262:14385–14388. [PubMed: 3312189]
Wei Y, Sowers JR, Clark SE, Li W, Ferrario CM, Stump CS (2008) Angiotensin II- induced skeletal muscle insulin resistance mediated by NF-kappaB activation via NADPH oxidase. Am J Physiol Endocrinol Metab 294:E345–E351
Sergeev IN, Rhoten WB (1995) 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology 136:2852–2861. [PubMed: 7789310]
Billaudel BJ, Faure AG, Sutter BC (1990) Effect of 1,25dihydroxyvitamin D3 on isolated islets from vitamin D3- deprived rats. Am J Phys 258:E643–E648
Norman AW, Frankel JB, Heldt AM, Grodsky GM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209(4458):823–825
Fujita T, Palmieri GM (2000) Calcium paradox disease: calcium deficiency prompting secondary hyperparathyroidism and cellular calcium overload. J Bone Miner Metab 18:109–125
Sooy K, Schermerhorn T, Noda M et al (1999) Calbindin-D (28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-D (28k) knockout mice and beta cell lines. J Biol Chem 274:34343–34349
Kadowaki S, Norman AW (1984) Pancreatic vitamin D-dependent calcium binding protein: biochemical properties and response to vitamin D. Arch Biochem Biophys 233(1):228–236
Cohen-Lahav M, Douvdevani A, Chaimovitz C et al (2007) The anti-inflammatory activity of 1,25- dihydroxyvitamin D3 in macrophages. J Steroid Biochem Mol Biol 103:558–562. [PubMed: 17267205]
Riachy R, Vandewalle B, Moerman E et al (2006) 1,25-Dihydroxyvitamin D3 protects human pancreatic islets against cytokine-induced apoptosis via down-regulation of the Fas receptor. Apoptosis 11:151–159. [PubMed: 16502254]
Gysemans CA, Cardozo AK, Callewaert H et al (2005) 1,25- Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in non-obese diabetic mice. Endocrinology 146(4):1956–1964
Tabesh M, Azadbakht L, Faghihimani E, Tabesh M, Esmaillzadeh A (2014) Calcium-vitamin D Cosupplementation influences circulating inflammatory biomarkers and Adipocytokines in vitamin D-insufficient diabetics: a randomized controlled clinical trial. JCEM 99(12):E2485–E2493
Oh JY, Barrett CE (2002) Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community- dwelling older adults: the Rancho Bernardo study. Metabolism 51(3):356–359
Palomer X, Gonzalez-Clemente JM, Blanco-Vaca F, Mauricio D (2008) Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab 10(3):185–197
Scragg R, Sowers MF, Bell C (2004) Serum 25-hydroxyvitamin D, diabetes and ethnicity in the third National Health and nutrition examination survey. Diabetes Care 27(12):2813–2818
Hypponen E, Boucher BJ, Berry DJ et al (2008) 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross sectional study in the 1958 British birth cohort. Diabetes 57(2):298–305
Mattila C, Laaksonen MA, Knekt P et al (2007) Serum 25- hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care 30(10):2569–2570
Song Y, Wang L, Pittas AG, Liana C (2013) Del Gobo. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes. A meta-analysis of prospective studies. Diabetes Care 36:1422–1428
Afzal S, Bojesen SE, Nordestgaard BG (2013) Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem 59:381–391. [PubMed: 23232064]
McDonnell SL, Baggerly LL, French CB, Heaney RP, Gorham ED, Holick MF, Scragg R, Garland CF (2016) Incidence rate of type 2 diabetes is >50% lower in grassroots health cohort with median serum 25–hydroxyvitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml. J Steroid Biochem Mol Biol 155:239–244
Stadlmayr A, Aigner E, Huber-Schönauer U, Niederseer D, Zwerina J, Husar-Memmer E, Hohla F, Schett G, Patsch W, Datz C (2015) Relations of vitamin D status, gender and type 2 diabetes in middle-aged Caucasians. Acta Diabetol 52:39–46
Pittas AG, Willett WC, Dawson-Hughes B et al (2006) Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 29(3):650–656
Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM (2005) Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older US women. Diabetes Care 28:2926–2932
Knekt P, Laaksonen M, Mattila C et al (2008) Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology 19(5):666–671
Fourohi NG, Luan J, Cooper A et al (2008) Baseline serum 25-hydroxy vitamin D is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely prospective study 1990-2000. Diabetes 57(10):2619–2625
Pittas AG, Harris SS, Stark PC, Wson-Hughes B (2007) The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 30:980–986
Nazarian S, Peter JVST, Boston RC, Jones SA, Mariash CN (2011) Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose. Transl Res 158(5):276–281
Mitri J, Dawson-Hughs B, Hu FB, Pittas AG (2011) Effects of viamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity and glycemia in adults at high risk of diabetes: the calcium and vitamin D for diabetes mellitus (CaDDM) randomized controlled trial. Am J Clin Nutr 94:486–494
Gagnon C, Daly RM, Carpentier A, Lu ZX, Shore-Lorenti C, Sikaris K, Jean S, Ebeling PR (2014) Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and b-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial. PLoS One 9(10):e109607
Zhao L-m, Tian X-q, Ge J-p, Yan-cheng X (2013) Vitamin D intake and type 2 diabetes risk: a meta-analysis of prospective cohort studies. Afr Health Sci 13(4):1130–1138
de Boer IH, Tinker LF, Connelly S et al (2008) Calcium plus vitamin D supplementation and the risk of incident diabetes in the Womens health initiative. Diabetes Care 31(4):701–707
Avenell A, Cook JA, MacLennan GS, McPherson GC (2009) Vitamin D supplementation and type 2 diabetes: a substudy of a randomized placebo controlled trial in older people (RECORD trial ISRCTN 51647438). Age Ageing 38:606–609
Mitchell DM, Leder BZ, Cagliero E, Mendoza N, Henao MP, Hayden DL, Finkelstein JS, Burnett-Bowie S-AM (2015) Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial. Am J Clin Nutr 102:385–392
Krul-Poel YHM, Westra S, ten Boekel E, ter Wee MM, van Schoor NM, van Wijland H, Stam F, Lips PTAM, Simsek S (2015 Aug) Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes (SUNNY trial): a randomized placebo-controlled trial. Diabetes Care 38(8):1420–1426
Elkassaby S, Harrison LC, Mazzitelli N, Wentworth JM, Colman PG, Spelman T, Fourlanos S (2014) A randomised controlled trial of high dose vitamin D in recent-onset type 2 diabetes. Diabetes Res Clin Pract 106:576–582
Tabesh M, Azadbakht L, Faghihimani E, Tabesh M, Esmaillzadeh A (2014) Effects of calcium–vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomised controlled clinical trial. Diabetologia 57:2038–2047
Kampmann U, Mosekilde L, Juhl C, Moller N, Christensen B, Rejnmark L, Wamberg L, Orskov L (2014) Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency a double-blind, randomized, placebo-controlled trial. Metab Clin Exp 63:1115–1124
Strobel F, Reusch J, Penna-Martinez M, Ramos-Lopez E (2014 Jan) Effect of a randomized controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus. Horm Metab Res 46(1):54–58
Nikooyeh B, Neyestani TR, Farvid M, Alavi-Majd H, Houshiarrad A, Kayali A et al (2011) Daily consumption of vitamin D- or vitamin D + calcium- fortified yogurt drink improved glycemic control in patients with type 2 DM: a randomized clinical trial. Am J Clin Nutr 93:764–771
Eftekhari MH, Akbarzadeh M, Dabbaghmanesh MH, Hasanzadeh J (2011) Impact of treatment with oral calcitriol on glucose indices in type 2 diabetes mellitus patients. Am J Clin Nutr 20(4):521–526
Peng Y, Li L-j (2015) Serum 25-hydroxyvitamin D level and diabetic nephropathy in patients with type 2 diabetes mellitus. Int Urol Nephrol 47:983–989
Wolf M, Shah A, Gutierrez O et al (2007) Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 72(8):1004–1013
Fernandez-Juarez G, Luno J, BArio V, De Venueza SG (2013 Nov) 25 (OH) vitamin D levels and renal disease progression in patients with type 2 diabetic nephropathy and blockade of the rennin-angiotensin system. Clin J Am Soc Nephrol 8(11):1870–1876
Zhang Y, Deb DK, Kong J et al (2009) Long-term therapeutic effect of vitamin D analog doxercalciferol on diabetic nephropathy: strong synergism with AT1 receptor antagonist. Am J Physiol Renal Physiol 297(3):F791–F801
Deb DK, Sun T, Wong KE, Zhang Z, Ning G, Zhang Y et al (2010) Combined vitamin D analog and AT1 receptor antagonist synergistically block the development of kidney disease in a model of type 2 diabetes. Int Soc Nephrol 77:1000–1009
de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyn D, Grimella T (2010) Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diebstes (VITAL study): a randomized controlled trial. Lancet 376:1543–1551
Kim MJ, Frankel AH, Donaldson M, Darch SJ, Pusey CD, Hill PD (2011) Oral cholecalciferol decreases albuminuria and urinary TGF-beta 1 in patients with type 2 diabetic nephropathy on established renin-angiotensin-aldostrerone system inhibition. Int Soc Nephrol 80:851–860
Li YC, Kong J, Wei M et al (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110:229–238
Milliez P, Girerd X, Plouin PF et al (2005) Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 45:1243–1248
Achinger SG, Ayus JC (2005) The role of vitamin D in left ventricular hypertrophy and cardiac function. Kidney Int Suppl 95:S37–S42
Cardus A, Parisi E, Gallego C et al (2006) 1,25-Dihydroxyvitamin D3 stimulates vascular smooth muscle cell proliferation through a VEGF-mediated pathway. Kidney Int 69:1377–1384
Koenig W, Sund M, Frohlich M et al (1999) C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (monitoring trends and determinants in cardiovascular disease) Augsburg cohort study, 1984 to 1992. Circulation 99:237–242
Kendrick J, Targher G, Smits G, Chonchol M (2009) 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the third National Health and nutrition examination survey. Atherosclerosis 205:255–260
Yan C, Chun-Ting Z, Zhe Z, Arthur W (2014) Tse hung fat, Yiu Kai hang. Association of myocardial dysfunction with vitamin D deficiency in patients with type 2 diabetes mellitus. J Diabetes Complicat 28:286–290
Herrmann M, Sullivan DR, Veillard A-S, McCorquodale T, Straub IR, Scott R, Laakso M, Topliss D, Jenkins AJ, Blankenberg S, Burton A, Keech AC (2015) Serum 25-Hydroxyvitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care 38:521–528. doi:10.2337/dc14-0180
Heidari B, Nargesi AA, Hafezi-Nejad N, Sheikhbahaei S, Pajouhi A, Nakhjavani M, Esteghamati A (2015) Assessment of serum 25-hydroxy vitamin D improves coronary heart disease risk stratification in patients with type 2 diabetes. Am Heart J 170:573–579.e5
Witham MD, Dove FJ, Dryburgh M, Sigden JA, Morris AD, Struthers AD (2010) The effecr of different doses of vitamin D3 on markers of vascular health in patients with type 2 diabetes: a randomized controlled trial. Diabetologia 53:2112–2119
Sugden JA, Davies JI, Witham MD, Mrrist AD, Struthers AD (2008) Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med 25:320–325
Soderstrom LH, Johnson SP (2012) Diaz1VA and Mainous AG 3rd. Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001–2004 NHANES. Diabet Med 29:50–55
Shehab D, Al-Jarallah K, Mojiminiyi OA, Al Mohamedy H, Abdella NA (2012) Does vitamin D deficiency play a role in peripheral neuropathy in type 2 diabetes? Diabet Med 29:43–49
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. ISRN Endocrinol 22(2013):641098
Lee P, Chen R (2008) Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain. Arch Intern Med 168:771–772
Shehab D, Al-Jarallah K, Abdella N, Olusegun A, Mojiminiyi HAM (2015) Prospective evaluation of the effect of short-term oral vitamin D supplementation on peripheral neuropathy in type 2 diabetes mellitus. Med Princ Pract 24:250–256. doi:10.1159/000375304
Aksoy H, Akçay F, Kurtul N, Baykal O, Avci B (2000) Serum 1,25Dihydroxy vitamin D (1,25(OH)2D3), 25 Hydroxy vitamin D (25(OH)D) and Parathormone levels in diabetic retinopathy. Clin Biochem 33(1):47–51
Alcubierre N, Valls J, Rubinat E, Cao G, Esquerda A, Traveset A, Granado-Casas M, Jurjo C, Mauricio D (2015) Vitamin D deficiency is associated with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus. J Diabetes Res, Article ID 374178, p 7. http://dx.doi.org/10.1155/2015/374178
Bhanuprakash Reddy G, Sivaprasad M, Shalini T, Satyanarayana A, Seshacharyulu M, Balakrishna N, Viswanath K, Sahay M (2015) Plasma vitamin D status in patients with type 2 diabetes with and without retinopathy. Nutrition 31:959–963
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Issa, C.M. (2017). Vitamin D and Type 2 Diabetes Mellitus. In: Ahmad, S. (eds) Ultraviolet Light in Human Health, Diseases and Environment. Advances in Experimental Medicine and Biology, vol 996. Springer, Cham. https://doi.org/10.1007/978-3-319-56017-5_16
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