RELATIONSHIP BETWEEN GESTATIONAL DIABETES MELLITUS AND VITAMIN D, CALCITONIN AND PARATHORMONE

Öz

ABSTRACT: Objective: There is growing evidence that Vitamin D has important role in glucose metabolism. Calcitonin and parathyroid hormone were not fully investigated in gestational diabetes mellitus (GDM). The aim of our study was to investigate the effects of vitamin D, calcitonin (Cal) and parathormone in GDM. Material and Methods: We evaluated retrospectively demographic and anthropometric parameters, vitamin D, active vitamin D, calcitonin and parathormone levels of 100 pregnant women including 50 with normal glucose metabolism and 50 with GDM whose ages and body mass indices (BMI) were similar in summer season. We classified the women according to age, parity, being veiled, BMI and vitamin D levels, and compared all parameters, then searched the correlation of all the parameters in groups and subgroups. Results: 25 hydroxy vitamin D (VitD) levels were non-significantly low in GDM and also in older, multiparous, veiled and obese GDM subgroups. Calcitonin and parathormone levels were not different in two groups. Vitamin D-deficient and obese GDM subgroups had significantly higher calcitonin levels than their opposite subgroups. There was a positive correlation between Cal and BMI in GDM, in Vit D deficient, older, or veiled GDM subgroups. Positive correlation between vitamin D and C peptide was found in only obese GDM. In logistic regression analysis including GDM subgroups and calcium metabolism hormones, except younger age (OR=0.116 (95% CI=0.04-0.338, p=<0.001)), VitD, active VitD, Cal, and PTH had no effect on GDM prediction. Conclusion: Although we could not find a significant difference in VitD, Cal and PTH levels of our GDM patients in summer season, we thought that VitD could play a role in obese GDM patients.We also concluded that Cal and PTH did not have roles in gestational diabetes mellitus. Larger, carefully designed studies including throughout pregnancy and postpartum periods and seasonal variations are required.

Anahtar Kelimeler

• gestational diabetes mellitus
• Vitamin D
• calcitonin
• parathormone

GESTASYONEL DİYABETES MELLİTUS İLE D VİTAMİNİ, KALSİTONİN VE PARATHORMON İLİŞKİSİ

Öz

ÖZET: Amaç: D vitamininin glukoz metabolizmasında önemli rol oynadığına dair kanıtlar artmaktadır. Kalsitonin ve paratiroid hormonu, gestasyonel diyabette tam olarak araştırılmamıştır. Çalışmamızın amacı gestasyonel diyabetes mellitusta (GDM) D vitamini, kalsitonin ve paratiroid hormonununun etkilerini araştırmaktır. Gereç ve Yöntemler: Retrospektif olarak yaz sezonunda 50 normal glukoz metabolizması (NGT) olan ve 50 gestasyonel diyabetli (GDM), toplam 100 gebe kadının demografik ve antropometrik parametrelerini, vitamin D, Aktif vitamin D, kalsitonin ve paratiroid hormon düzeylerini değerlendirdik. Kadınları yaş, parite, örtülü olup olmama, vücut kitle indeksi (VKİ) ve vitamin D düzeylerine göre sınıflandırdık ve tüm parametreleri karşılaştırdık, daha sonra tüm parametrelerin diyabetik grupta ve alt gruplarda korelasyonunu araştırdık. Bulgular: GDM grubunda ve ayrıca ileri yaş, multipar, örtülü ve obez GDM alt gruplarında 25 hidroksi vitamin D düzeyi istatistiksel anlamlı olmayan derecede düşüktü. Kalsitonin ve paratiroid hormon düzeyleri iki grupta farklı değildi. D vitamini eksikliği olan ve obez GDM alt gruplarının kalsitonin seviyeleri, kendi karşıt alt gruplarından belirgin olarak daha yüksekti. GDM'de, Vit D eksikliği olan, yaşlı veya örtülü GDM alt gruplarında kalsitonin ile VKİ arasında pozitif bir korelasyon vardı. Vitamin D ile C peptid arasında ise sadece obez GDM alt grubunda pozitif korelasyon saptandı. GDM alt grupları ve kalsiyum metabolizma hormonlarını içeren lojistik regresyon analizinde, genç yaş hariç (OR= 0.116 (% 95 CI = 0.04-0.338, p = <0.001)), VitD, aktif VitD, kalsiyum ve PTH'nin GDM öngörme üzerine etkisi yoktu. Sonuç: Yaz mevsiminde GDM hastalarımızda D vitamini, parathormon ve kalsitonin düzeylerinde anlamlı bir fark bulunamamasına rağmen, D vitaminin obez GDM hastalarında rol oynayabileceğini düşündük. Ayrıca Cal ve PTH'nin gestasyonel diabetes mellitusta rolü olmadığı sonucuna vardık. Tüm gebelik ve doğum sonrası dönemleri ve mevsimsel farklılıkları içeren geniş çaplı prospektif çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• gestasyonel diabetes mellitus
• vitamin D
• kalsitonin
• parathormon

Kaynakça

1. 1. Egan AM, Dow ML, Vella A. A Review of the Pathophysiology and Management of Diabetes in Pregnancy [published online ahead of print, 2020 Jul 28]. Mayo Clin Proc. 2020; S0025-6196(20)30202-0.
2. 2. Rosen CJ, Donahau LR, Hunter SJ. Insulin like growth factors and bone: the osteoporosis connection. Proc Soc Exp Biol Med.1994;206:83-102.3. Lee NK, Karsenty G. Reciprocal regulation of bone and energy metabolism. J Muskuloskelet Neuronal Interact. 2008; 19:161-6.
3. 3. Mizokami A, Yasutake Y, Gao J, et al.Osteocalcin induces release of glucagon-like peptide-1 and thereby stimulates insulin secretion in mice. PLoS One. 2013;8(2): e57375.
4. 4.Mizokami A, Yasutake Y, Higashi S, et al. Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion. Bone. 2014; 69:68-79.
5. 5.Winhofer Y, Handisurya A, Tura A, Bittighofer C, Klein K. Osteocalcin is related to enhanced insulin secretion in gestational diabetes mellitus. Diabetes Care. 2010; 33:139-43.
6. 6. Alemzadeh R, Kichler J, Babar G, Calhoun M. Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism. 2008; 57:183-91.
7. 7. Chonchol M, Scragg R. 25-Hydroxyvitamin D, insulin resistance, and kidney function in the Third National Health and Nutrition Examination Survey. Kidney Int. 2007; 71:134-9.
8. 8. Farrant HJF, Krishnaveni GV, Hill JC, et al. Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size. Eur J Clin Nutr.2009; 63:646-52.

9. 9. Park S, Yoon H, Ryu H, et al. Maternal vitamin D deficiency in early pregnancy is not associated with gestational diabetes mellitus development or pregnancy outcomes in Korean Pregnant women in a prospective study. J Nutr Sci Vitaminol. 2014; 60:269-75.
10. 10. Al-Daghri NM, Al-Attas OS, Al-Okail MS, et al. Severe hypovitaminosis D is widespread and more common in non-diabetics than diabetics in Saudi adults. Saudi Med J. 2010; 31:775-80.
11. 11. Eggemoen ÅR, Waage CW, Sletner L, Gulseth HL, Birkeland KI, Jenum AK. Vitamin D, Gestational Diabetes, and Measures of Glucose Metabolism in a Population-Based Multiethnic Cohort. J Diabetes Res. 2018; 2018:8939235.
12. 12. Hu L, Zhang Y, Wang X, You L, Xu P, Cui X, Zhu L, Ji C, Guo X, Wen J. Maternal Vitamin D Status and Risk of Gestational Diabetes: A Meta-Analysis. Cell Physiol Biochem. 2018;45(1):291-300.
13. 13.Wilson RL, Leviton AJ, Leemaqz SY, et al. Vitamin D levels in an Australian and New Zealand cohort and the association with pregnancy outcome. BMC Pregnancy Childbirth. 2018;18(1):251.
14. 14. Kim HS, Hwang HS, Kwon HS, Lim JY, Sohn IS. A comparative analysis of maternal and fetal 25-hydroxyvitamin D in pregnant women with and without gestational diabetes mellitus. J Matern Fetal Neonatal Med. 2018 Oct;31(20):2748-55.
15. 15. Cho GJ, Hong SC, Oh MJ, Kim HJ. Vitamin D deficiency in gestational diabetes mellitus and the role of the placenta. Am J Obstet Gynecol. 2013;209(6): 560.e1-560.e5608.
16. 16. Zuhur SS, Erol RS, Kuzu I, Altuntas Y. The relationship between low maternal serum 25-hydroxyvitamin D levels and gestational diabetes mellitus according to the severity of 25-hydroxyvitamin D deficiency. Clinics (Sao Paulo). 2013;68(5):658-64.
17. 17. Schaerström R, Hamfelt A, Söderhjelm L. Parathyroid hormone and calcitonin in diabetes mellitus. Ups J Med Sci. 1986;91(1):99-104.
18. 18. Metzger BE, Gabbe SG, Persson B. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010; 33:676-82.
19. 19. Amraei M, Mohamadpour S, Sayehmiri K, Mousavi SF, Shirzadpour E, Moayeri A. Effects of Vitamin D Deficiency on Incidence Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis. Front Endocrinol (Lausanne). 2018; 9:7.
20. 20. Senti J, Thiele DK, Anderson CM. Maternal vitamin D status as a critical determinant in gestational diabetes. J. Obstet. Gynecol. Neonatal. Nurs. 2012, 41, 328–38.
21. 21. Lau SL, Gunton JE, Athayde NP, et al. Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: A double-blind randomized controlled clinical trial. Am. J. Clin. Nutr. 2013, 98, 1425–32.
22. 22. Moan J, Lagunova Lindberg F, Poronjnicu AC. Seasonal variation of 1,25 dihdroxy vitamin D and its association with body mass index and age. J Steroid Biochem Mol Biol. 2009; 113:217-21.
23. 23. Need AG, O’Loughlin PD, Horowitz M, Nordin BE. Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxy vitamin D in postmenopausal women. Clin Endocrinol (Oxf). 2005; 62:738-41.
24. 24. Tai K, Need AG, Horowitz M, Chapman IM. Vitamin D, glucose, insulin, and insulin sensitivity. Nutrition.2008;24:279-85.
25. 25. Beaulieu C, Kestekian R, Havrankova J, Gascon-Barre M.Calcium is essential in normalizing intolerance to glucose that accompanies vitamin D depletion in vivo. Diabetes. 1993; 42:35-43.
26. 26. Kovacs CS. Calcium and bone metabolism in pregnancy and lactation. J Clin Endocrinol Metab. 2001; 86:2344-48.
27. 27. Sergeev, I.N.; Rhoten, W.B. 1,25-dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology 1995, 136, 2852–61.
28. 28. Matheu C, Gysemans C. Vitamin D and diabetes. Diabetologia. 2005; 48:1247-57.
29. 29. Flores M. A role of vitamin D in low intensity chronic inflammation and insulin resistance in type 2 diabetes mellitus. Nutr Res Rev. 2005; 18:175-82.
30. 30. Moan J, Lagunova Lindberg F, Poronjnicu AC. Seasonal variation of 1,25 dihdroxy vitamin D and its association with body mass index and age. J Steroid Biochem Mol Biol. 2009; 113:217-21.
31. 31. Ahlman T, Sjoberg HE, Bucht E. Calcium homeostasis in normal pregnancy and puerperium. Acta Obstet Gynecol Scand. 1994; 73:393-8.
32. 32. Glorieux FH, Arabian A, Delvin EE. Pseudo vitamin D deficiency: absence of 25-hydroxyvitamin D 1 alpha hdroxylase activity in human placenta decidual cells. J Clin Endocrinol Metab. 1995;800: 2255-58.
33. 33. Schaerström R, Hamfelt A, Söderhjelm L.Parathyroid hormone and calcitonin in diabetes mellitus. Ups J Med Sci.1986; 91:99-104.
34. 34. Simmonds CS, Kovacs CS. Role of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in regulating mineral homeostasis during fetal development. Crit. Rev. Eukaryot. Gene Expr. 2010, 20, 235–73.
35. 35. Avila E, Diaz L, Barrera D, et al. Regulation of vitamin D hydroxylases gene expression by 1,25-dihydroxyvitamin D3 and cyclic AMP in cultured human syncytiotrophoblasts. J. Steroid Biochem. Mol. Biol. 2007, 103, 90–6.
36. 36. Nachankar A, Kotwal N, Upreti V, Verma V, Hari Kumar KVS. Association of Vitamin D and Parathyroid Hormone with Insulin Sensitivity, Beta Cell Function and Gestational Diabetes in Pregnancy: A Cross-Sectional, Observational Study. Diabetes Ther. 2018 Oct;9(5):2081-90.