This retrospective cohort study aimed to determine whether severe calcidiol deficiency [25-hydroxyvitamin (OH)D <30 nmol/L] improvement has a beneficial effect on cardiometabolic parameters in children and adolescents (5-17 years) with or without metabolic syndrome (MetS). Logistic regression analysis was performed to test for multivariate associations between potential confounders and changes in vitamin D (VD) status from baseline to follow-up care when predicting binary categorical outcomes. Of 562 participants, 146 (26%) had MetS. Individuals with severe VD deficiency (VDD) were more likely to have MetS with elevated blood pressure than those with sufficient (≥75 nmol) VD levels (adjusted odds ratio [AOR], 4.46; 1.08-18.43; p < .05) at follow-up. In the logistic regression model, every unit increase in VD across time decreased the odds of MetS (AOR, 0.98; 95% confidence interval: [0.96, 0.99]; p < .05). Improvement in VD status demonstrated a beneficial metabolic effect in children and adolescents with severe VDD.
NCD Risk Factor Collaboration (NCD-RisC). 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. 2017;390:2627-2642. doi:10.1016/S0140-6736(17)32129-3.
2.
NoubiapJJNansseuJRLontchi-YimagouE, et alGlobal, regional, and country estimates of metabolic syndrome burden in children and adolescents in 2020: a systematic review and modelling analysis. Lancet Child Adolesc Health. 2022;6:158-170. doi:10.1016/S2352-4642(21)00374-6.
3.
ChissiniRBCKuschnirMCde OliveiraCL, et alCutoff values for HOMA-IR associated with metabolic syndrome in the study of cardiovascular risk in adolescents (ERICA Study). Nutrition. 2020;71:110608. doi:10.1016/j.nut.2019.110608.
4.
FiteAWangLSeyoumB.Vitamin D deficiency is associated with metabolic syndrome. J Diabetes Complicat. 2020;1:1-8. doi:10.31487/j.JDMC.2020.01.03.
5.
ChallaASMakariouSESiomouEC.The relation of vitamin D status with metabolic syndrome in childhood and adolescence: an update. J Pediatr Endocrinol Metab. 2015;28:1235-1245. doi:10.1515/jpem-2014-0485.
6.
IsartFAIsart-InfanteFJHeidelER, et alAcanthosis nigricans is a strong predictor of low blood calcidiol levels in children and adolescents. Metab Syndr Relat Disord. 2022;20:509-516. doi:10.1089/met.2022.0005.
7.
Melguizo-RodríguezLCostela -RuizVJGarcía-RecioE, et alRole of vitamin D in the metabolic syndrome. Nutrients. 2021;13:830. doi:10.3390/nu13030830.
8.
TheikNWYRajiOEShenwaiP, et alRelationship and effects of vitamin D on metabolic syndrome: a systematic review. Cureus. 2021;13:e17419. doi:10.7759/cureus.17419.
9.
MooreCELiuY.Elevated systolic blood pressure of children in the United States is associated with low serum 25-hydroxyvitamin D concentrations related to body mass index: national Health and Examination survey 2007–2010. Nutr Res. 2017;38:64-70. doi:10.1016/j.nutres.2017.01.008.
10.
FuZXuCShuY, et alSerum 25-hydroxyvitamin D is associated with obesity and metabolic parameters in US children. Public Health Nutr. 2020;23:1214-1222. doi:10.1017/S1368980019001137.
11.
MunnsCFShawNKielyM, et alGlobal consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab. 2016;101:394-415. doi:10.1210/jc.2015-2175.
12.
RossACMansonJEAbramsSA, et alThe 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-58. doi:10.1210/jc.2010-2704.
13.
ZhangYTanHTangJ, et alEffects of vitamin D Supplementation on prevention of Type 2 diabetes in patients with prediabetes: a systematic review and meta-analysis. Diabetes Care. 2020;43:1650-1658. doi:10.2337/dc19-1708.
14.
MansonJECookNRLeeIM, et alVitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380:33-44. doi:10.1056/NEJMoa1809944.
15.
WeissRDziuraJBurgertTS, et alObesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004;350:2362-2374. doi:10.1056/NEJMoa031049.
16.
SkinnerACSteinerMJChungAE, et alCholesterol curves to identify population norms by age and sex in healthy weight children. Clin Pediatr (Phila). 2012;51:233-237. doi:10.1177/0009922811430344.
17.
BurrowsRCorrea-BurrowsPReyesM, et alHealthy Chilean adolescents with HOMA-IR ≥ 2.6 have increased cardiometabolic risk: association with genetic, biological, and environmental factors. J Diabetes Res. 2015;2015:783296. doi:10.1155/2015/783296.
18.
ClarkeNJ. Vitamin D Testing. Increasing Accuracy, Improving Patient Management. San Juan Capistrano, CA: Clinical Education Center, Quest-Nichols Institute. Accessed January 1, 2023. https://www.questdiagnostics.com.
19.
ChenHMcCoyLFSchleicherRL, et alMeasurement of 25-hydroxyvitamin D3 (25OHD3) and 25-hydroxyvitamin D2 (25OHD2) in human serum using liquid chromatography-tandem mass spectrometry and its comparison to a radioimmunoassay method. Clin Chim Acta. 2008;391:6-12. doi:10.1016/j.cca.2008.01.017.
20.
QuHQLiQRentfroAR, et alThe definition of insulin resistance using HOMA-IR for Americans of Mexican descent using machine learning. PLoS ONE. 2011;6:e21041. doi:10.1371/journal.pone.0021041.
21.
MatthewsDRHoskerJPRudenskiAS, et alHomeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419. doi:10.1007/BF00280883.
22.
HillNRLevyJCMatthewsDR.Expansion of the homeostasis model assessment of β-cell function and insulin resistance to enable clinical trial outcome modeling through the interactive adjustment of physiology and treatment effects: iHOMA2. Diabetes Care. 2013;36:2324-2330. doi:10.2337/dc12-0607.
23.
GanjiVZhangXShaikhN, et alSerum 25-hydroxyvitamin D concentrations are associated with prevalence of metabolic syndrome and various cardiometabolic risk factors in US children and adolescents based on assay-adjusted serum 25-hydroxyvitamin D data from NHANES 2001–2006. Am J Clin Nutr. 2011;94:225-233. doi:10.3945/ajcn.111.013516.
24.
OlsonMLMaaloufNMOdenJD, et alVitamin D deficiency in obese children and its relationship to glucose homeostasis. J Clin Endocrinol Metab. 2012;97:279-285. doi:10.1210/jc.2011-1507.
25.
ShulhaiAMPavlyshynHOleksandraS, et alThe association between vitamin D deficiency and metabolic syndrome in Ukrainian adolescents with overweight and obesity. Ann Pediatr Endocrinol Metab. 2022;27:113-120. doi:10.6065/apem.2142158.079.
26.
ChristakosSAjibadeDVDhawanP, et alVitamin D: metabolism. Endocrinol Metab Clin North Am. 2010;39:243-253. doi:10.1016/j.ecl.2010.02.002.
27.
HolickMFBinkleyNCBischoff-FerrariHA, et alEvaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930. doi:10.1210/jc.2011-0385.
28.
MarinoRMisraM.Extra-skeletal effects of vitamin D. Nutrients. 2019;11:1460. doi:10.3390/nu11071460.
29.
CaiBLuoXZhangP, et alEffect of vitamin D supplementation on markers of cardiometabolic risk in children and adolescents: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis. 2021;31:2800-2814. doi:10.1016/j.numecd.2021.06.013.
30.
HaugerHLaursenRPRitzC, et alEffects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr. 2020;59:873-884. doi:10.1007/s00394-019-02150-x.
31.
FeriraAJLaingEMHausmanDB, et alVitamin D supplementation does not impact insulin resistance in black and white children. J Clin Endocrinol Metab. 2016;101:1710-1718. doi:10.1210/jc.2015-3687.
32.
RouhaniPHajhashemyZSaneeiP.Circulating serum vitamin D levels in relation to metabolic syndrome in children: a systematic review and dose–response meta-analysis of epidemiologic studies. Obes Rev. 2021;22:e13314. doi:10.1111/obr.13314.
33.
ÇelikNDoğanHOZararsizG.Different threshold levels of circulating total and free 25-hydroxyvitamin D for the diagnosis of vitamin D deficiency in obese adolescents. Eur J Pediatr. 2021;180:2619-2627. doi:10.1007/s00431-021-04137-5.
34.
KhayyatzadehSSMirmoosaviSJFazeliM, et alHigh-dose vitamin D supplementation is associated with an improvement in several cardio-metabolic risk factors in adolescent girls: a nine-week follow-up study. Ann Clin Biochem. 2018;55:227-235. doi:10.1177/0004563217707784.
35.
WeissRBremerAALustigRH.What is metabolic syndrome, and why are children getting it?Ann N Y Acad Sci. 2013;1281:123-140. doi:10.1111/nyas.12030.
36.
WangHHLeeDKLiuM, et alNovel insights into the pathogenesis and management of the metabolic syndrome. Pediatr Gastroenterol Hepatol Nutr. 2020;23:189-230. doi:10.5223/pghn.2020.23.3.189.
37.
SlyperAHKashmerLHuangWM, et alAcanthosis nigricans, vitamin D, and insulin resistance in obese children and adolescents. J Pediatr Endocrinol Metab. 2014;27:1107-1111. doi:10.1515/jpem-2013-0465.
38.
SharifiFMousavinasabNMellatiAA.Defining a cutoff point for vitamin D deficiency based on insulin resistance in children. Diabetes Metab Syndr. 2013;7:210-213. doi:10.1016/j.dsx.2013.10.015.
39.
MansbachJMGindeAACamargoCA.Serum 25-hydroxyvitamin D levels among US children aged 1 to 11 years: do children need more vitamin D?Pediatrics. 2009;124:1404-1410. doi:10.1542/peds.2008-2041.
40.
WangDSuKDingZ, et alAssociation of vitamin D receptor gene polymorphisms with metabolic syndrome in Chinese children. Int J Gen Med. 2021;14:57-66. doi:10.2147/IJGM.S287205.
41.
RajakumarKMooreCGKhalidAT, et alEffect of vitamin D3 supplementation on vascular and metabolic health of vitamin D deficient overweigh and obese children: a randomized clinical trial. Am J Clin Nutr. 2020;111:757-768.
42.
WilliamsRNovickMLehmanE.Prevalence of hypovitaminosis D and its association with comorbidities of childhood obesity. Perm J. 2014;18:32-39. doi:10.7812/TPP/14-016.
43.
HerrickKAStorandtRJAffulJ, et alVitamin D status in the United States, 2011–2014. Am J Clin Nutr. 2019;110:150-157. doi:10.1093/ajcn/nqz037.
44.
VanderwallCEickhoffJRandallCR, et alBMI z-score in obese children is a poor predictor of adiposity changes over time. BMC Pediatr. 2018;18:187. doi:10.1186/s12887-018-1160-5.
45.
FreedmanDSWooJGDanielsSR.Longitudinal changes in various BMI metrics and adiposity in 3- to 7-year-olds. Pediatrics. 2022;150:e2022058302. doi:10.1542/peds.2022-058302.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
