Biopolym. Cell. 2011; 27(2):85-92.
Reviews
Role of vitamin D in modulating gestational diabetes
1, 2, 3Arora Chander P.
  1. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center; Burns-Allen Research Institute and the Division of Maternal-Fetal Medicine
    Los Angeles, USA
  2. David Geffen School of Medicine, University of California
    Los Angeles, USA
  3. International Research and Innovation Management; Burns-Allen Research Institute; Department of Academic Affairs, Cedars-Sinai Medical Center
    Los Angeles, USA

Abstract

Low maternal levels of major circulating form of vitamin D could be a perplexing factor that leads to expression of gestational diabetes mellitus (GDM). Insufficient or deficient levels of vitamin D may allow diabetic insult during pregnancy leading to gestational diabetes and inducing changes in a variety of key functional molecules and gene expression. Autocrine metabolism of vitamin D promotes anti-inflammatory response to maternal decidua and fetal trophoblasts. Immunomodulatory actions of vitamin D are likely to be compromised under conditions of low vitamin D levels with potential detrimental physiological consequences. Recent data are now available to implicate autocrine/paracrine impact of maternal vitamin D status can result in both increased insulin resistance and reduced insulin secretion, linking inflammation to metabolic disorder in the mother. Insulin and cytokines are the main contributors to the cascade of events and potential regulators of placental function in GDM. This article aims at exploring the possible mechanisms underlying GDM that could be regulated by pleotropic effects of vitamin D
Keywords: vitamin D, gestational diabetes, placenta, insulin, immune response

References

[1] Lehmann B. The vitamin D3 pathway in human skin and its role for regulation of biological processes Photochem. Photobiol 2005 81, N 6 P. 1246–1251.
[2] Holick M. F. McCollum Award Lecture, 1994: vitamin D – new horizons for the 21st century Am. J. Clin. Nutr 1994 60, N 4 P. 619–630.
[3] Ritz E., Boland R., Kreusser W. Effects of vitamin D and parathyroid hormone on muscle: potential role in uremic myopathy Am. J. Clin. Nutr 1980 33, N 7 P. 1522–1529.
[4] Arora C. P., Hobel C. J. Vitamin D - a novel role in pregnancy Biopolym. Cell 2010 26, N 2 P. 97–104.
[5] Dawson-Hughes B., Heaney R. P., Holick M. F., Lips P., Meunier P. J., Vieth R. Estimates of optimal vitamin D status Osteoporos. Int 2005 16, N 7 P. 713–716.
[6] Arora C. P., Hobel C. J. Vitamin D – a novel role in pregnancy Biopolym. Cell 2010 26, N 2 P. 97–104.
[7] Wolf M., Sauk J., Shah A., Smirnakis K. V., Jimenez-Kimble R., Ecker J. L., Thandhani R. Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus Diabetes Care 2004 27, N 1 P. 21–27.
[8] Kaufmann P., Mayhew T. M., Charnock-Jones D. S. Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy Placenta 2004 25, N 2 P. 114 –126.
[9] Mayhew T. M. Fetoplacental angiogenesis during gestation is biphasic, longitudinal and occurs by proliferation and remodelling of vascular endothelial cells Placenta 2002 23, N 10 P. 742–750.
[10] Radaelli T., Varastehpour A., Catalano P., Hauguel-de Mouzon S. Gestational diabetes induces placental genes for chro nic stress and inflammatory pathways Diabetes 2003 52, N 12 P. 2951–2958.
[11] Ategbo J M., Grissa O., Yessoufou A., Hichami A., Dramane K. L., Moutairou K., Miled A., Grissa A., Jerbi M., Tabka Z., Khan N. A. Modulation of adipokines and cytokines in gestational diabetes and macrosomia J. Clin. Endocrinol. Metab 2006 91, N 10 P. 4137–4143.
[12] Raghupathy R. Pregnancy: success and failure within the Th1/ Th2/Th3 paradigm Semin. Immunol 2001 13, N 4 P. 219– 227.
[13] Reinhard G., Noll A., Schlebusch H., Mallmann P., Ruecker A. V. Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes Biochem. Biophys. Res. Commun 1998 245, N 3 P. 933–938.
[14] Radaelli T., Uvena-Celebrezze J., Minium J., Huston-Presley L., Catalano P., Hauguel de Mouzon S. Maternal interleukin-6: marker of fetal growth and adiposity J. Soc. Gynecol. Investig 2006 13, N 1 P. 53–57.
[15] Retnakaran R., Hanley A. J., Raif N., Connelly P. W., Sermer M., Zinman B. C-reactive protein and gestational diabetes: the central role of maternal obesity J. Clin. Endocrinol. Metab 2003 88, N 8 P. 3507–3512.
[16] Ramsay J. E., Ferrell W. R., Crawford L., Wallace A. M., Greer I. A., Sattar N. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways J. Clin. Endocrinol. Metab 2002 87, N 9 P. 4231–4237.
[17] Rajala M. W., Scherer P. E. Minireview: the adipocyte – at the crossroads of energy homeostasis, inflammation, and atherosclerosis Endocrinology 2003 144, N 9 P. 3765–3773.
[18] Guerre-Millo M. Adipose tissue and adipokines: for better or worse Diabete Metab 2004 30, N 1 P. 13–19.
[19] Desoye G., Hartmann M., Blaschitz A., Dohr G., Hahn T., Kohnen G., Kaufmann P. Insulin receptors in syncytiotrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern Histochemistry 1994 101, N 4 P. 277–285.
[20] Desoye G., Hartmann M., Jones C. J., Wolf H. J., Kohnen G., Kosanke G., Kaufmann P. Location of insulin receptors in the placenta and its progenitor tissues Microsc. Res. Tech 1997 38, N 1–2 P. 63–75.
[21] Hiden U., Maier A., Bilban M., Ghaffari-Tabrizi N., Wadsack C., Lang I., Dohr G., Desoye G. Insulin control of placental gene expression shifts from mother to foetus over the course of pregnancy Diabetologia 2006 49, N 1 P. 123–131.
[22] Desoye G., Korgun E. T., Ghaffari-Tabrizi N., Cetin I., Hahn T. Selective upregulation of placental glycogenin-2 in gestational diabetes is independent of hyperglycemia or hyperinsulinemia J. Soc. Gynecol. Investig 2004 11, suppl P. 299A.
[23] Hoegh M., Minium J., Bernard A., Varastehpour A., Catalano P., Hauguel de Mouzon S. Placental contribution to maternal adiponectin and resistin in late pregnancy J. Soc. Gynecol. Investig 2005 12, suppl P. 229A.
[24] Chen H. L., Yang Y. P., Hu X. L., Yelavarthi K. K., Fishback J. L., Hunt J. S. Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation Am. J. Pathol 1991 139, N 2 P. 327– 335.
[25] Phillips T. A., Ni J., Hunt J. S. Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are transcribed in human placentae, cytotrophoblasts, placental macrophages and placental cell lines Placenta 2001 22, N 8–9 P. 663– 672.
[26] Challier J., Galtier M., Bintein T., Cortez A., Lepercq J., Hauguelde Mouzon S. Placental leptin receptor isoforms in normal and pathological pregnancies Placenta 2003 24, N 1 P. 92–99.
[27] Kauma S. W., Herman K., Wang Y., Walsh S. W. Differential mRNA expression and production of interleukin-6 in placental trophoblast and villous core compartments Am. J. Reprod. Immunol 1993 30, N 2–3 P. 131–135.
[28] Lepercq J., Challier J. C., Guerre-Millo M., Cauzac M., Vidal H., Hauguel-de Mouzon S. Prenatal leptin production: evidence that fetal adipose tissue produces leptin J. Clin. Endocrinol. Metab 2001 86, N 6 P. 2409–2413.
[29] Kirwan J. P., Hauguel-De Mouzon S., Lepercq J., Challier J. C., Huston-Presley L., Friedman J. E., Kalhan S. C., Catalano P. M. TNF-alpha is a predictor of insulin resistance in human pregnancy Diabetes 2002 51, N 7 P. 2207–2213.
[30] Lepercq J., Cauzac M., Lahlou N., Timsit J., Girard J., Auwerx J., Hauguel-de Mouzon S. Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin Diabetes 1998 47, N 5 P. 847–850.
[31] Boucher B. J. Inadequate vitamin D status: does it contribute to the disorders comprising syndrome «X»? Br. J. Nutr 1998 79, N 4 P. 315–327.
[32] McKeigue P. M., Pierpoint T., Ferrie J. E., Marmot M. G. Relationship of glucose intolerance and hyperinsulinaemia to body fat pattern in south Asians and Europeans Diabetologia 1992 35, N 8 P. 785–791.
[33] Baynes K. C., Boucher B. J., Feskens E. J., Kromhout D. Vitamin D, glucose tolerance and insulinaemia in elderly men Diabetologia 1997 40, N 3 P. 344–347.
[34] Hotamisligil G. S., Spiegelman B. M. Tumor necrosis factor alpha: a key component of the obesity-diabetes link Diabetes 1994 43, N 11 P. 1271–1278.
[35] Allegra V., Luisetto G., Mengozzi G., Martimbianco L., Vasile A. Glucose-induced insulin secretion in uremia: role of 1 alpha, 25(HO)2-vitamin D3 Nephron 1994 68, N 1 P. 41–47.
[36] Stene L. C., Ulriksen J., Magnus P., Joner G. Use of cod liver oil during pregnancy associated with lower risk of type I diabetes in the offspring Diabetologia 2000 43, N 9 P. 1093–1098.
[37] Hypponen E., Laara E., Reunanen A., Jarvelin M. R., Virtanen S. M. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study Lancet 2001 358, N 9292 P. 1500–1503.
[38] Statistisches Bundesamt Gesundheitsbericht fur Deutschland 1998. Diabetes Mellitus Stuttgart: Metzler und Poeschel, 1998 P. 237–242.
[39] Chang T. J., Lei H. H., Yeh J. I., Chiu K. C., Lee K. C., Chen M. C., Tai T. Y., Chuang L. M. Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population Clin. Endocrinol. (Oxf.)–2000 52, N 5 P. 575–580.
[40] Ortlepp J. R., Lauscher J., Hoffmann R., Hanrath P., Joost H. G. The vitamin D receptor gene variant is associated with the prevalence of type 2 diabetes mellitus and coronary artery disease Diabet. Med 2001 18, N 10 P. 842–845.
[41] Bell N. H., Epstein S., Greene A., Shary J., Oexmann M. J., Shaw S. Evidence for alteration of the vitamin D-endocrine system in obese subjects J. Clin. Invest 1985 76, N 1 P. 370– 373.
[42] Wortsman J., Matsuoka L. Y., Chen T. C., Lu Z., Holick M. F. Decreased bioavailability of vitamin D in obesity Am. J. Clin. Nutr. 2000; 72, N 3 P. 690–693.
[43] Evans K. N., Bulmer J. N., Kilby M. D., Hewison M. Vitamin D and placental-decidual function J. Soc. Gynecol. Investig 2004 11, N 5 P. 263–271.
[44] Zehnder D., Evans K. N., Kilby M. D., Bulmer J. N., Innes B. A., Stewart P. M., Hewison M. The ontogeny of 25-hydroxyvitamin D(3) 1alpha-hydroxylase expression in human placenta and decidua Am. J. Pathol 2002 161, N 1 P. 105–114.
[45] Staeva-Vieira T. P., Freedman L. P. 1,25-dihydroxyvitamin D3 inhibits IFN-gamma and IL-4 levels during in vitro polarization of primary murine CD4+ T cells J. Immunol 2002 168, N 3 P. 1181–1189.
[46] Hill J. A., Polgar K., Anderson D. J. T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion JAMA 1995 273, N 24 P. 1933–1936.
[47] Lemire J. M., Archer D. C., Beck L., Spiegelberg H. L. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions J. Nutr 1995 125, N 6 (Suppl.) P. 1704S–1708S.
[48] Challis J. R., Lockwood C. J., Myatt L., Norman J. E., Strauss J. F. 3rd, Petraglia F. Inflammation and pregnancy Reprod. Sci 2009 16, N 2 P. 206–215.
[49] Weiss G., Goldsmith L. T., Taylor R. N., Bellet D., Taylor H. S. Inflammation in reproductive disorders Reprod. Sci 2009 16, N 2 P. 216–229.
[50] Romero R., Espinoza J., Goncalves L. F., Kusanovic J. P., Friel L., Hassan S. The role of inflammation and infection in preterm birth Semin. Reprod. Med 2007 25, N 1 P. 21–39.
[51] El-Shazly S., Makhseed M., Azizieh F., Raghupathy R. Increased expression of pro-inflammatory cytokines in placentas of women undergoing spontaneous preterm delivery or premature rupture of membranes Am. J. Reprod. Immunol 2004 52, N 1 P. 45–52.
[52] Dudley D. J. Pre-term labor: an intra-uterine inflammatory response syndrome? J. Reprod. Immunol 1997 36, N 1–2 P. 93–109.
[53] Thacher T. D., Clarke B. L. Vitamin D insufficiency Mayo. Clin. Proc 2011 86, N 1 P. 50–60.
[54] Morris H. A., Anderson P. H. Autocrine and paracrine actions of vitamin D Clin. Biochem. Rev 2010 31, N 4 P. 129–138.
[55] Jeffery L. E., Burke F., Mura M., Zheng Y., Qureshi O. S., Hewison M., Walker L. S., Lammas D. A., Raza K., Sansom D. M. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3 J. Immunol 2009 183, N 9 P. 5458–5467.