Vitamin D, vitamin D-binding protein and parathyroid hormone in children and adolescents with obesity and dysfunction of the hypothalamus
DOI:
https://doi.org/10.15574/PP.2023.94.97Keywords:
hypothalamus dysfunction, obesity, children, vitamin D, parathyroid hormone, vitamin D-binding proteinAbstract
According to modern concepts, hypothalamic dysfunction (HD) is a neuroendocrine syndrome caused by dysfunction of the hypothalamic-pituitary system and is manifested mainly by hormonal and metabolic disorders and vegetative-vascular disorders. Adolescent obesity, associated in many cases with HD, and with a high risk of developing vitamin D (vitD) deficiency. Obesity in association with HD and vitD deficiency causes serious health problems, and the vitD/parathyroid hormone (PTH) axis plays a potential role in their etiopathogenesis.
Purpose - to study the relationship between vitD, vitamin D-binding protein (VDBP) and parathyroid hormone levels in adolescents with obesity against the background of HD.
Materials and methods. The serum level of vitD was determined by the immunochemiluminescence method on microparticles (Abbott, USA) in 87 children and adolescents with overweight/obesity against the background of HD aged 10-16 years. The VDBP level was determined using enzyme-linked immunospecific assay (ELISA) with commercial standard kit Elabsciense Biotechnology Co., Ltd (USA). The PTH level - by immunochemiluminescence assay with commercial standard kit Monobind (USA).
Results. Insufficiency of vitD was noted in 32.2%, deficiency - in 56.3% of patients. The severity of obesity was associated with the levels of vitD: a decrease in the level of vitD in children and adolescents with overweight (69.30±5.14 nmol/l) and the I stage of obesity (52.60±4.17 nmol/l), a significant deficiency of vitD in persons with the II and III stages of obesity (36.20±3.75 nmol/l, 23.10±3.12 nmol/l respectively). A significant decrease of vitD level in obese patients was accompanied by a significant increase of the PTH level. In the III stage of obesity, the level of PTH was twice as high as the level of PTH in practically healthy children and adolescents with normal MT and in patients with excess body weight (p<0.05). With a body mass index (BMI) >30 kg/m2, there was a significant decrease in the content of vitD, associated with a significant increase in the level of PTH and a sharp decrease in the level of VDBP. The level of VDBP had a positive correlation with vitD level and a negative relationship with BMI. A significant decrease in the content of VDBP (58.71±18.43 ng/ml)) was established in comparison with a group of practically healthy children and adolescents with normal body weight (141.65±25.34 ng/ml) (р<0.05).
Conclusions. The results indicate the presence of certain changes in the PTH/vitD/VDBP axis in children and adolescents with excess body weight/obesity against the background of HD, which are an integral part of the complex manifestation of the disease. Maintaining an adequate vitD status can contribute to the prevention of such disorders.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
References
Akter R, Afrose A, Sharmin S, Rezwan R, Rahman MR, Neelotpol S. (2022). A comprehensive look into the association of vitamin D levels and vitamin D receptor gene polymorphism with obesity in children. Biomed Pharmacother. 153: 113285. https://doi.org/10.1016/j.biopha.2022.113285; PMid:35728355
Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, Köstenberger M, Tmava Berisha A et al. (2020). Vitamin D deficiency 2.0: an update on the current status worldwide. Eur J Clin Nutr. 74 (11): 1498-1513. https://doi.org/10.1038/s41430-020-0558-y; PMid:31959942 PMCid:PMC7091696
Bahlous A, Krir A, Mrad M, Bouksila M, Kalai S, Kilani O et al. (2022). Vitamin D in healthy Tunisian population: Preliminary results. J Med Biochem. 41 (2): 168-175. https://doi.org/10.5937/jomb0-30247; PMid:35510205 PMCid:PMC9010047
Barja-Fernández S, Aguilera CM, Martínez-Silva I, Vazquez R, Gil-Campos M, Olza et al. (2018). 25-Hydroxyvitamin D levels of children are inversely related to adiposity assessed by body mass index. J Physiol Biochem. 74 (1): 111-118. https://doi.org/10.1007/s13105-017-0581-1; PMid:28744831
Bivona G, Gambino CM, Iacolino G, Ciaccio M. (2019). Vitamin D and the nervous system. Neurol Res. 41 (9): 827-835. https://doi.org/10.1080/01616412.2019.1622872; PMid:31142227
Botsyurko VI. (2014). Hypothalamic syndrome. In 100 selected lectures on endocrinology (second edition). Eds. Yu.I. Karachentsev, A.V. Kazakov, N.A. Kravchun, I.M. Ilyina. Kharkov: «S.A.M.»: 776-781.
Chun RF. (2012). New perspectives on the vitamin D binding protein. Cell Biochem Funct. 30 (6): 445-456. https://doi.org/10.1002/cbf.2835; PMid:22528806
Corica D, Zusi C, Olivieri F, Marigliano M, Piona C, Fornari E et al. (2019). Vitamin D affects insulin sensitivity and β-cell function in obese non-diabetic youths. Eur J Endocrinol. 181 (4): 439-450. https://doi.org/10.1530/EJE-19-0369; PMid:31408845
Cunha KA, Magalhães EI, Loureiro LM, Sant'Ana LF, Ribeiro AQ, Novaes JF. (2015). Calcium intake, serum vitamin D and obesity in children: is there an association? Rev Paul Pediatr. 33 (2): 222-229. https://doi.org/10.1016/j.rpped.2015.03.001; PMid:25890445 PMCid:PMC4516377
Delanghe JR, Speeckaert R, Speeckaert MM. (2015, Oct). Behind the scenes of vitamin D binding protein: more than vitamin D binding. Best Pract Res Clin Endocrinol Metab. 29 (5): 773-786. https://doi.org/10.1016/j.beem.2015.06.006; PMid:26522461
Emerging Risk Factors Collaboration; Wormser D, Kaptoge S, Di Angelantonio E, Wood AM, Pennells L et al. (2011). Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet. 377 (9771): 1085-1095. https://doi.org/10.1016/S0140-6736(11)60105-0; PMid:21397319
Fiamenghi VI, Mello ED. (2021). Vitamin D deficiency in children and adolescents with obesity: a meta-analysis. J Pediatr (Rio J). 97 (3): 273-279. https://doi.org/10.1016/j.jped.2020.08.006; PMid:33022267 PMCid:PMC9432231
Frolova TV, Osman NS. (2022). Structural and functional state of bone tissue in children during the second growth spurt. Modern Pediatrics. Ukraine. 1 (121): 31-35. https://doi.org/10.15574/SP.2022.121.31
Fu Z, Xu C, Shu Y, Xie Z, Lu C, Mo X. (2020). Serum 25-hydroxyvitamin D is associated with obesity and metabolic parameters in US children. Public Health Nutr. 23 (7): 1214-1222. https://doi.org/10.1017/S1368980019001137; PMid:31120008 PMCid:PMC10200621
Grama A, Burac L, Aldea CO, Bulata B, Delean D, Samasca G et al. (2020). Vitamin D-binding protein (Gc-globulin) in acute liver failure in children. Diagnostics (Basel). 10 (5): 278. https://doi.org/10.3390/diagnostics10050278; PMid:32375318 PMCid:PMC7278011
Gutiérrez Medina S, Gavela-Pérez T, Domínguez-Garrido MN, Gutiérrez-Moreno E, Rovira A, Garcés C, Soriano-Guillén L. (2015). The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance. J Pediatr Endocrinol Metab. 28 (1-2): 105-110. https://doi.org/10.1515/jpem-2014-0033; PMid:25153219
Harms LR, Cowin G, Eyles DW, Kurniawan ND, McGrath JJ, Burne TH. (2012). Neuroanatomy and psychomimetic-induced locomotion in C57BL/6J and 129/X1SvJ mice exposed to developmental vitamin D deficiency. Behav Brain Res. 230 (1): 125-131. https://doi.org/10.1016/j.bbr.2012.02.007; PMid:22343129
Hedesan OC, Fenzl A, Digruber A, Spirk K, Baumgartner-Parzer S, Bilban M, et al. (2019). Parathyroid hormone induces a browning program in human white adipocytes. Int J Obes (Lond). 43 (6): 1319-1324. https://doi.org/10.1038/s41366-018-0266-z; PMid:30518824 PMCid:PMC6411131
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Holmøy T, Moen SM. (2010). Assessing vitamin D in the central nervous system. Acta Neurol Scand Suppl. 190: 88-92. https://doi.org/10.1111/j.1600-0404.2010.01383.x; PMid:20586743
Jiang L, Tian W, Wang Y, Rong J, Bao C, Liu Y et al. (2012). Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis. Joint Bone Spine. 79 (3): 291-297. https://doi.org/10.1016/j.jbspin.2011.05.015; PMid:21803633
Karampela I, Sakelliou A, Vallianou N, Christodoulatos GS, Magkos F, Dalamaga M. (2021). Vitamin D and Obesity: Current Evidence and Controversies. Curr Obes Rep. 10 (2): 162-180. https://doi.org/10.1007/s13679-021-00433-1; PMid:33792853
Kelishadi R, Farajzadegan Z, Bahreynian M. (2014). Association between vitamin D status and lipid profile in children and adolescents: a systematic review and meta-analysis. Int J Food Sci Nutr. 65 (4): 404-410. https://doi.org/10.3109/09637486.2014.886186; PMid:24524677
Khizhnyak OO, Plekhova EI, Sulima TN. (2003). The role of hereditary and environmental factors in the formation of the hypothalamic syndrome of the pubertal period in boys. Endocrinology. 8 (2): 221-227.
Khundmiri SJ, Murray RD, Lederer E. (2016). PTH and vitamin D. Compr Physiol. 6 (2): 561-601. https://doi.org/10.1002/cphy.c140071; PMid:27065162
Kir S, Komaba H, Garcia AP, Economopoulos KP, Liu W, Lanske B et al. (2016). PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer. Cell Metab. 23 (2): 315-323. https://doi.org/10.1016/j.cmet.2015.11.003; PMid:26669699 PMCid:PMC4749423
Kir S, White JP, Kleiner S, Kazak L, Cohen P, Baracos VE, Spiegelman BM. (2014). Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. 513 (7516): 100-104. doi: 10.1038/nature13528.https://doi.org/10.1038/nature13528; PMid:25043053 PMCid:PMC4224962
Klish WJ, Skelton JA. (2019). Definition; epidemiology; and etiology of obesity in children and adolescents. Up To Date: 12-26.
Kumar S, Kelly AS. (2017). Review of childhood obesity: From epidemiology, etiology, and comorbidities to clinical assessment and treatment. Mayo Clin Proc. 92 (2): 251-265. https://doi.org/10.1016/j.mayocp.2016.09.017; PMid:28065514
Lang F, Ma K, Leibrock CB. (2019). 1,25(OH)2D3 in brain function and neuropsychiatric disease. Neurosignals. 27 (1): 40-49. https://doi.org/10.33594/000000182; PMid:31769259
Lee WM, Emerson DL, Werner PA, Arnaud P, Goldschmidt-Clermont P, Galbraith RM. (1985, Mar-Apr). Decreased serum group-specific component protein levels and complexes with actin in fulminant hepatic necrosis. Hepatology. 5 (2): 271-275. https://doi.org/10.1002/hep.1840050220; PMid:4038965
Lin CI, Chang YC, Kao NJ, Lee WJ, Cross TW, Lin SH. (2020). 1,25(OH)2D3 alleviates Aβ(25-35)-induced tau hyperphosphorylation, excessive reactive oxygen species, and apoptosis through interplay with glial cell line-derived neurotrophic factor signaling in SH-SY5Y cells. Int J Mol Sci. 21 (12): 4215. https://doi.org/10.3390/ijms21124215; PMid:32545801 PMCid:PMC7352552
Marushko YuV, Hyshchak TV. (2021). Prevention of vitamin D deficiency in children. The state of the problem in the world and in Ukraine. Modern pediatrics. Ukraine. 4 (116): 36-45. https://doi.org/10.15574/SP.2021.116.36
NCD Risk Factor Collaboration (NCD-RisC). (2017). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 390 (10113): 2627-2642. https://doi.org/10.1016/S0140-6736(17)32129-3; PMid:29029897
Patriota P, Borloz S, Ruiz I, Bouthors T, Rezzi S, Marques-Vidal P, Hauschild M. (2022). High prevalence of hypovitaminosis D in adolescents attending a Reference Centre for the Treatment of Obesity in Switzerland. Children (Basel). 9 (10): 1527. https://doi.org/10.3390/children9101527; PMid:36291463 PMCid:PMC9601272
Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB. (2015). Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev. 16 (4): 341-349. https://doi.org/10.1111/obr.12239; PMid:25688659
Pop TL, Sîrbe C, Benţa G, Mititelu A, Grama A. (2022). The role of vitamin D and vitamin D binding protein in chronic liver diseases. Int J Mol Sci. 23 (18): 10705. https://doi.org/10.3390/ijms231810705; PMid:36142636 PMCid:PMC9503777
Rafiq S, Jeppesen PB. (2018). Is hypovitaminosis D related to incidence of type 2 diabetes and high fasting glucose level in healthy subjects: A systematic review and meta-analysis of Observational Studies. Nutrients. 10 (1): 59. https://doi.org/10.3390/nu10010059; PMid:29320437 PMCid:PMC5793287
Rendina-Ruedy E, Rosen CJ. (2022). Parathyroid hormone (PTH) regulation of metabolic homeostasis: An old dog teaches us new tricks. Mol Metab. 60: 101480. https://doi.org/10.1016/j.molmet.2022.101480; PMid:35338013 PMCid:PMC8980887
Samuel L, Borrell LN. (2013). The effect of body mass index on optimal vitamin D status in U.S. adults: the National Health and Nutrition Examination Survey 2001-2006. Ann Epidemiol. 23 (7): 409-414. https://doi.org/10.1016/j.annepidem.2013.05.011; PMid:23790345
Shulhai AMA, Pavlyshyn HA, Shulhai OM. (2019). Peculiarities of the prevalence and risk factors for vitamin D deficiency in overweight and obese adolescents in Ukraine. Arch Balk Med Union. 54 (1): 57-63. https://doi.org/10.31688/ABMU.2019.54.1.08
Singh GM, Danaei G, Farzadfar F, Stevens GA, Woodward M, Wormser D et al. (2013). The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS One. 8 (7): e65174. https://doi.org/10.1371/journal.pone.0065174; PMid:23935815 PMCid:PMC3728292
Soheilipour F, Hamidabad NM. (2022). Vitamin D and calcium status among adolescents with morbid obesity undergoing bariatric surgery. Obes Surg. 2 (3): 738-741. https://doi.org/10.1007/s11695-021-05809-9; PMid:34799812
Speeckaert MM, Speeckaert R, Delanghe JR. (2021). Vitamin D and vitamin D binding protein: the inseparable duo in COVID-19. J Endocrinol Invest. 44 (10): 2323-2324. https://doi.org/10.1007/s40618-021-01573-w; PMid:33840080 PMCid:PMC8038533
Ströhle A. (2011). The updated recommendations of the US Institute of Medicine (IOM) on the intake of vitamin D. A critical appraisal. Med Monatsschr Pharm. 34 (8): 291-298.
Turer CB, Lin H, Flores G. (2013). Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics. 131 (1): e152-61. https://doi.org/10.1542/peds.2012-1711; PMid:23266927
Van Cromphaut SJ, Rummens K, Stockmans I, Van Herck E, Dijcks FA, Ederveen AG et al. (2003). Intestinal calcium transporter genes are upregulated by estrogens and the reproductive cycle through vitamin D receptor-independent mechanisms. J Bone Miner Res. 18 (10): 1725-1736. https://doi.org/10.1359/jbmr.2003.18.10.1725; PMid:14584880
Wakayo T, Whiting SJ, Belachew T. (2016). Vitamin D deficiency is associated with overweight and/or obesity among schoolchildren in Central Ethiopia: A Cross-Sectional Study. Nutrients. 8 (4): 190. https://doi.org/10.3390/nu8040190; PMid:27043619 PMCid:PMC4848659
Wojcik M, Janus D, Kalicka-Kasperczyk A, Sztefko K, Starzyk JB. (2017). The potential impact of the hypovitaminosis D on metabolic complications in obese adolescents - Preliminary results. Ann Agric Environ Med. 24 (4): 636-639. https://doi.org/10.5604/12321966.1230676; PMid:29284239
Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. (2000). Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 72 (3): 690-693. https://doi.org/10.1093/ajcn/72.3.690; PMid:10966885
Yanai H, Yoshida H. (2019). Beneficial effects of adiponectin on glucose and lipid metabolism and atherosclerotic progression: Mechanisms and perspectives. Int J Mol Sci. 20 (5): 1190. https://doi.org/10.3390/ijms20051190; PMid:30857216 PMCid:PMC6429491
Yao Y, Zhu L, He L, Duan Y, Liang W, Nie Z et al. (2015). A meta-analysis of the relationship between vitamin D deficiency and obesity. Int J Clin Exp Med. 8 (9): 14977-14984.
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