Gestational Diabetes and Vitamin D - many studies

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Gestational Diabetes: 30% increase in US since 2016 (reported July 2023)

Gestational diabetes impacts nearly 75,000 pregnant individuals and their unborn babies each year in the United States, and according to the Centers for Disease Control cases have risen 30% since 2016.
Which is probably similar to the increase of Diabetes in the same time period

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Disrupted placental vitamin D metabolism and calcium signaling in gestational diabetes and pre-eclampsia patients - April 2023

Endocrine . 2023 Apr;80(1):191-200. doi: 10.1007/s12020-022-03272-9
Shweta Varshney # 1, Ramu Adela # 1 2, Garima Kachhawa 3, Reema Dada 4, Vidushi Kulshreshtha 3, Rajesh Kumari 3, Ramesh Agarwal 5, Rajesh Khadgawat 6

Introduction: Gestational diabetes (GDM) and pre-eclampsia (PE) represents the unrecognized risk factors for reduced bone content in neonates. The present study is planned to explore the components of vitamin D metabolism and calcium transport in placenta of GDM and PE cases and its effect on the neonatal bone mass determination using bone densitometry system.

Methods: We have collected serum and placenta tissues from GDM (n = 20), PE (n = 20), and healthy pregnancies (n = 20). In the present study, we found mRNA expression of oxidative stress markers, vitamin D metabolic components and calcium channels, calcium channel binding proteins, plasma membrane calcium ATPase, ATP synthase and Ca2+ release genes; Ryanodine receptors genes were assessed by quantitative real-time PCR (qRT-PCR) in placental tissue of GDM, PE, and healthy pregnancies.

Results: We observed high level of oxidative stress in both GDM and PE placenta compared to normal pregnancies.

• CYP2R1 and VDR mRNA expression was significantly downregulated and
• upregulation of CYP27B1 and CYP24A1 in GDM and PE compared with healthy cases.

Similarly, calcium transporters were downregulated in GDM and PE placental tissues. In addition, CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression were correlated with BMC of neonates.

Discussion: Oxidative stress is probably relevant to disrupted vitamin D homeostasis and calcium transport in the placenta of GDM and PE cases. The altered regulatory mechanism of CYP24A1 and VDR could indicates more pronounced serum 25(OH)D reduction. Additionally, reduced BMC in the neonates of these cases might be as consequences of modified CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression.
Other Genes

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>30 ng of Vitamin D in 2nd tri. associated with 39% less risk of Gestational Diabetes - April 2024

Maternal vitamin D status and risk of gestational diabetes mellitus in twin pregnancies: a longitudinal twin pregnancies birth cohort study
Nutr J. 2024 Apr 10;23(1):41. doi: 10.1186/s12937-024-00944-2.
Da-Yan Li # 1 2 3, Lan Wang # 3 4, Li Li 3 4, Shuwei Zhou 3 4, Jiangyun Tan 3 4, Chunyan Tang 3 4, Qianqian Liao 3 4, Ting Liu 3 4, Li Wen 5 6, Hong-Bo Qi 7 8

Background: Gestational diabetes mellitus (GDM) is a common complication of pregnancy, with significant short-term and long-term implications for both mothers and their offspring. Previous studies have indicated the potential benefits of vitamin D in reducing the risk of GDM, yet little is known about this association in twin pregnancies. This study aimed to investigate maternal vitamin D status in the second trimester and examine its association with the risk of GDM in twin pregnancies.

Methods: We conducted a prospective cohort study based on data from the Chongqing Longitudinal Twin Study (LoTiS). Peripheral blood serum was collected from the mothers in the second trimester to measure 25(OH)D concentrations. GDM was diagnosed at 23-26 weeks of gestation using a 75-g 2-h oral glucose tolerance test. We used multivariable logistic regression analyses to examine the correlations between vitamin D status and the risk of GDM.

Results: Of the total participants, 93 (29.9%) women were diagnosed with GDM. The mean serum 25(OH)D concentration in the second trimester was 31.1 ± 11.2 ng/mL, and the rate of vitamin D insufficiency and deficiency were 23.5% and 18.7%, respectively. Compared to women with a 25(OH)D concentration < 30 ng/mL, those with a 25(OH)D concentration ≥ 30 ng/mL had a significantly lower risk of GDM (RR 0.61; 95% CI: 0.43, 0.86), especially those who were overweight before pregnancy (RR 0.32; 95% CI: 0.16, 0.64). The restricted cubic splines model showed an inverted J-shaped relationship between vitamin D concentrations and GDM risk.

Conclusions: The risk of GDM was significantly reduced in twin pregnant women with vitamin D concentrations ≥ 30 ng/mL in the second trimester.

Trial registration: ChiCTR-OOC-16,008,203. Retrospectively registered on 1 April 2016.
Some of the References

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• Zhu WW, Fan L, Yang HX, Kong LY, Su SP, Wang ZL, Hu YL, Zhang MH, Sun LZ, Mi Y, et al. Fasting plasma glucose at 24–28 weeks to screen for gestational diabetes mellitus: new evidence from China. Diabetes Care. 2013;36:2038–40.
• Coustan DR, Lowe LP, Metzger BE, Dyer AR. International Association of D, pregnancy study G: the hyperglycemia and adverse pregnancy outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus. Am J Obstet Gynecol. 2010;202:e654651–656. -
• Fatima K, Asif M, Nihal K, Hussain HU, Hasan AW, Zahid M, Burney MH, Asad F, Fatima S, Saleem MB, Khalid MA. Association between vitamin D levels in early pregnancy and gestational diabetes mellitus: a systematic review and meta-analysis. J Family Med Prim Care. 2022;11:5569–80.
• Milajerdi A, Abbasi F, Mousavi SM, Esmaillzadeh A. Maternal vitamin D status and risk of gestational diabetes mellitus: a systematic review and meta-analysis of prospective cohort studies. Clin Nutr. 2021;40:2576–86.
• Shang M, Zhao N. Early pregnancy vitamin D insufficiency and gestational diabetes mellitus. J Obstet Gynaecol Res. 2022;48:2353–62.
• Aslan Cin NN, Yalcin M, Yardimci H. Vitamin D Deficiency during the first trimester of pregnancy and the risk of developing gestational diabetes Mellitus. J Obstet Gynecol Neonatal Nurs. 2022;51:526–35.
• Xia J, Song Y, Rawal S, Wu J, Hinkle SN, Tsai MY, Zhang C. Vitamin D status during pregnancy and the risk of gestational diabetes mellitus: a longitudinal study in a multiracial cohort. Diabetes Obes Metab. 2019;21:1895–905.
• Chen P, Li M, Mu Y, Wang Y, Liu Z, Li Q, Li X, Dai L, Xie Y, Liang J, Zhu J. Temporal trends and adverse perinatal outcomes of twin pregnancies at differing gestational ages: an observational study from China between 2012–2020. BMC Pregnancy Childbirth. 2022;22:467.
• Ashwal E, Berger H, Hiersch L, Yoon EW, Zaltz A, Shah B, Halperin I, Barrett J, Melamed N. gestational diabetes and fetal growth in twin compared with singleton pregnancies. Am J Obstet Gynecol. 2021;225:420. e421-420 e413. -
• Lai FY, Johnson JA, Dover D, Kaul P. Outcomes of singleton and twin pregnancies complicated by pre-existing diabetes and gestational diabetes: a population-based study in Alberta, Canada, 2005-11. J Diabetes. 2016;8:45–55.
• Luo ZC, Simonet F, Wei SQ, Xu H, Rey E, Fraser WD. Diabetes in pregnancy may differentially affect neonatal outcomes for twins and singletons. Diabet Med. 2011;28:1068–73.
• Simoes T, Queiros A, Correia L, Rocha T, Dias E, Blickstein I. gestational diabetes mellitus complicating twin pregnancies. J Perinat Med. 2011;39:437–40.
• Hiersch L, Berger H, Okby R, Ray JG, Geary M, McDonald SD, Murray-Davis B, Riddell C, Halperin I, Hasan H, et al. gestational diabetes mellitus is associated with adverse outcomes in twin pregnancies. Am J Obstet Gynecol. 2019;220:102. e101-102 e108. -
• Dave ED, Bodnar LM, Vani K, Himes KP. Perinatal outcomes in twin pregnancies complicated by gestational diabetes. Am J Obstet Gynecol MFM. 2021;3:100396.
• Alkaabi J, Almazrouei R, Zoubeidi T, Alkaabi FM, Alkendi FR, Almiri AE, Sharma C, Souid AK, Ali N, Ahmed LA. Burden, associated risk factors and adverse outcomes of gestational diabetes mellitus in twin pregnancies in Al Ain, UAE. BMC Pregnancy Childbirth. 2020;20:612.
• Tward C, Barrett J, Berger H, Kibel M, Pittini A, Halperin I, Cohen H, Melamed N. Does gestational diabetes affect fetal growth and pregnancy outcome in twin pregnancies? Am J Obstet Gynecol. 2016;214:e653651–658. -
• Lin D, Fan D, Li P, Chen G, Rao J, Zhou Z, Zhang H, Luo X, Ma H, Feng J, et al. Perinatal outcomes among twin pregnancies with gestational diabetes mellitus: a nine-year retrospective cohort study. Front Public Health. 2022;10:946186.
• Mei Y, Yu J, Wen L, Fan X, Zhao Y, Li J, Qiao J, Fu H, Leong P, Saffery R, et al. Perinatal outcomes and offspring growth profiles in twin pregnancies complicated by gestational diabetes mellitus: a longitudinal cohort study. Diabetes Res Clin Pract. 2021;171:108623.
• Wen L, Chen Y, Liu T, Wang Y, Baker PN, Qi H, Wang L. Different subtypes of gestational diabetes mellitus are associated with distinct perinatal outcomes in twin pregnancies. Diabetes Res Clin Pract. 2023;204:110920.
• Tong C, Wen L, Wang L, Fan X, Zhao Y, Liu Y, Wang X, Huang S, Li J, Li J et al. Cohort Profile: the Chongqing Longitudinal Twin Study (LoTiS). Int J Epidemiol 2022.
• Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine S. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.
• International Association of D, Pregnancy Study Groups, Consensus P, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva A, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33:676–82. -
• Yin WJ, Tao RX, Hu HL, Zhang Y, Jiang XM, Zhang MX, Jin D, Yao MN, Tao FB, Zhu P. The association of vitamin D status and supplementation during pregnancy with gestational diabetes mellitus: a Chinese prospective birth cohort study. Am J Clin Nutr. 2020;111:122–30.
• Shao B, Mo M, Xin X, Jiang W, Wu J, Huang M, Wang S, Muyiduli X, Si S, Shen Y, et al. The interaction between prepregnancy BMI and gestational vitamin D deficiency on the risk of gestational diabetes mellitus subtypes with elevated fasting blood glucose. Clin Nutr. 2020;39:2265–73.
• Wang L, Yu T, Jiao R, Fan X, Wang Y, Liu W, Wang S, Xie J, Zhao C. The association between vitamin D levels in the second trimester of pregnancy and gestational diabetes mellitus. J Obstet Gynaecol Res. 2022;48:2748–55.
• Cheng Y, Chen J, Li T, Pei J, Fan Y, He M, Liu S, Liu J, Zhang Q, Cheng H. Maternal vitamin D status in early pregnancy and its association with gestational diabetes mellitus in Shanghai: a retrospective cohort study. BMC Pregnancy Childbirth. 2022;22:819.
• Chen GD, Pang TT, Li PS, Zhou ZX, Lin DX, Fan DZ, Guo XL, Liu ZP. Early pregnancy vitamin D and the risk of adverse maternal and infant outcomes: a retrospective cohort study. BMC Pregnancy Childbirth. 2020;20:465.
• Wilson RL, Leviton AJ, Leemaqz SY, Anderson PH, Grieger JA, Grzeskowiak LE, Verburg PE, McCowan L, Dekker GA, Bianco-Miotto T, Roberts CT. Vitamin D levels in an Australian and New Zealand cohort and the association with pregnancy outcome. BMC Pregnancy Childbirth. 2018;18:251.
• Luo C, Li Z, Lu Y, Wei F, Suo D, Lan S, Ren Z, Jiang R, Huang F, Chen A, et al. Association of serum vitamin D status with gestational diabetes mellitus and other laboratory parameters in early pregnant women. BMC Pregnancy Childbirth. 2022;22:400.
• Salakos E, Rabeony T, Courbebaisse M, Taieb J, Tsatsaris V, Guibourdenche J, Senat MV, Haidar H, Jani JC, Barglazan D, et al. Relationship between vitamin D status in the first trimester of pregnancy and gestational diabetes mellitus - A nested case-control study. Clin Nutr. 2021;40:79–86.
• Magnusdottir KS, Tryggvadottir EA, Magnusdottir OK, Hrolfsdottir L, Halldorsson TI, Birgisdottir BE, Hreidarsdottir IT, Hardardottir H, Gunnarsdottir I. Vitamin D status and association with gestational diabetes mellitus in a pregnant cohort in Iceland. Food Nutr Res 2021, 65.
• Wen J, Hong Q, Zhu L, Xu P, Fu Z, Cui X, You L, Wang X, Wu T, Ding H, et al. Association of maternal serum 25-hydroxyvitamin D concentrations in second and third trimester with risk of gestational diabetes and other pregnancy outcomes. Int J Obes (Lond). 2017;41:489–96.
• Pham TTM, Huang YL, Chao JC, Chang JS, Chen YC, Wang FF, Bai CH. Plasma 25(OH)D concentrations and gestational diabetes Mellitus among pregnant women in Taiwan. Nutrients 2021, 13.
• Yaribeygi H, Maleki M, Sathyapalan T, Iranpanah H, Orafai HM, Jamialahmadi T, Sahebkar A. The molecular mechanisms by which vitamin D improve glucose homeostasis: a mechanistic review. Life Sci. 2020;244:117305.
• Mohd Ghozali N, Giribabu N, Salleh N. Mechanisms Linking Vitamin D Deficiency to Impaired Metabolism: An Overview. Int J Endocrinol 2022, 2022:6453882.
• Retnakaran R, Shah BR. Impact of Twin Gestation and fetal sex on maternal risk of diabetes during and after pregnancy. Diabetes Care. 2016;39:e110–111.
• Rauh-Hain JA, Rana S, Tamez H, Wang A, Cohen B, Cohen A, Brown F, Ecker JL, Karumanchi SA, Thadhani R. Risk for developing gestational diabetes in women with twin pregnancies. J Matern Fetal Neonatal Med. 2009;22:293–9.
• Papachatzopoulou E, Chatzakis C, Lambrinoudaki I, Panoulis K, Dinas K, Vlahos N, Sotiriadis A, Eleftheriades M. Abnormal fasting, post-load or combined glucose values on oral glucose tolerance test and pregnancy outcomes in women with gestational diabetes mellitus. Diabetes Res Clin Pract. 2020;161:108048.

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39+ VitaminDWiki pages have GESTATIONAL DIABETES in the title

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VitaminDWiki – Genetics category contains

343 articles in the Genetics category

see also

• Vitamin D Receptor has 530 items
• Vitamin D Binding Protein = GC has 178 items
• CYP27B1 has 63 items
• CYP24A1 in title of 34+ items
• CYP2R1 25+ items
• Calcidiol has 48 items
• Calcitriol has 62 items
• Topical Vitamin D
• Nanoemulsion Vitamin D may be a substantially better form
• 1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
• CYP3A4 (7 as of Dec 2022)
• Getting Vitamin D into your body
• 

Vitamin D blood test misses a lot

• Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
• Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
• A Vitamin D test in cells rather than blood was feasible (2017 personal communication)   Commercially available 2019
  • However, test results would vary in each tissue due to multiple genes
• Good clues that Vitamin D is being restricted from getting to the cells
  1) A vitamin D-related health problem runs in the family
      especially if it is one of 51+ diseases related to Vitamin D Receptor
  2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
  3) DNA and VDR tests - 100 to 200 dollars $100 to $250
  4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
     Genes are good, have enough Magnesium, etc.
  5) Back Pain
     probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
  • The founder of VitaminDWiki took action with clues #3&5

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VitaminDWiki - Pregnancy category contains

920 items in Pregnancy category

 - see also

• Overview Pregnancy and vitamin D
• Number of articles in both categories of Pregnancy and:Dark Skin 29;   Depression 21;   Diabetes 44;   Obesity 17;  Hypertension 44;   Breathing 35;  Omega-3 44;  Vitamin D Receptor 24 Click here for details
• All items in category Infant/Child 854 items
• Pregnancy needs at least 40 ng of vitamin D, achieved by at least 4,000 IU – Hollis Aug 2017
• 38+ papers with Breastfed etc, in the title
• Call to action – more Vitamin D for pregnancies, loading doses are OK – Holick Aug 2019
• 53+ preeclampsia studies
• 94+ studies with PRETERM in the title
• Fertility problem (PCOS) reduced by vitamin D, etc: many studies 15+
• 94+ Gestational Diabetes
• Caesarean birth much more likely if low Vitamin D - many studies 15+ studies
• Post-partum depression and low Vitamin D - many studies 15+ studies
• Stillbirth reduced by Vitamin D, Zinc, Omega-3 - several studies 5+ studies
• Search VitaminDWiki for "Assisted reproduction" 33 items as of Aug 2022
• Fertility and Sperm category listing has 142 items along with related searches
• (Stunting OR “low birth weight” OR LBW) 1180 items as of June 2020
• Less labor pain if higher level of vitamin D – August 2021
• Healthy pregnancies need lots of vitamin D
• Ensure a healthy pregnancy and baby - take Vitamin D before conception
  

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VitaminDWiki - 24 studies in both categories Pregnancy and VDR

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