维生素D治疗肥胖合并非酒精性脂肪肝儿童的临床研究

doi:10.11852/zgetbjzz2022-0367

摘要/Abstract

摘要： 目的分析肥胖合并非酒精性脂肪肝(NAFLD)儿童血清25羟维生素D[25(OH)D]水平以及补充维生素D(VD)对NAFLD的疗效,为VD用于儿童NAFLD治疗提供临床依据。方法 1)2020年1月—2021年8月,纳入102名6～14周岁的肥胖儿童,依据肝脏超声分为肥胖合并NAFLD组和肥胖无NAFLD组;并纳入健康体检儿童作为对照组。比较3组儿童血清25(OH)D、血脂、转氨酶及胰岛素抵抗指数(HOMA-IR)等指标的差异。2)将58名肥胖合并NAFLD患儿随机分为:VD干预组和VD非干预组。两组儿童均予以饮食运动指导,VD干预组在此基础上补充骨化三醇800 U/d,共16周。检测并比较两组儿童干预前后各项指标的变化。结果 1)肥胖合并NAFLD 组血清25(OH)D水平[(20.94±6.88) ng/ml]显著低于肥胖无NAFLD组[(24.31±7.69) ng/ml, P＜0.05]及健康对照组[(29.19±5.44) ng/ml, P＜0.01]。且血清25(OH)D水平与BMI及HOMA-IR呈负相关(r＝-0.37、－0.71, P＜0.01)。2)肥胖合并NAFLD 组的VD缺乏及不足率(84.48%)高于肥胖无NAFLD组(68.18%)及健康对照组(35.00%),差异具有统计学意义(χ²＝25.85, P＜0.01)。3)干预前,VD干预组和VD非干预组各项指标无显著差异,而干预 16周后VD干预组血清25(OH)D水平显著高于VD非干预组(t＝2.22, P＜0.05),血脂、转氨酶、BMI、HOMA-IR水平均显著低于VD非干预组(P＜0.05),脂肪肝病变也有显著改善。结论肥胖合并NAFLD儿童普遍存在VD不足。补充VD能有效提高其血清25(OH)D水平,改善肝功能、高血脂、胰岛素抵抗及脂肪肝病变。

关键词: 维生素D, 儿童, 肥胖, 非酒精性脂肪肝病, 胰岛素抵抗

Abstract: Objective To analyze the level of serum 25 hydroxyvitamin D[25 (OH)D] in obese children with non-alcoholic fatty liver disease (NAFLD) and the effect of vitamin D (VD) supplements on NAFLD, and to provide a clinical basis for VD in the treatment of children with NAFLD. Methods 1) From January 2020 to August 2021, 102 obese children aged 6 to 14 years were enrolled in this study and were divided into two groups according to liver ultrasound results:obesity with NAFLD group (n=58) and obesity without NAFLD group (n=44). Meanwhile, 40 healthy children were included as controls. The differences of serum 25(OH)D, lipid, transaminase and homoeostasis model assessment of insulin resistance (HOMA-IR) among the three groups were compared. 2) Fifty eight obese children with NAFLD were randomly divided into VD intervention group and VD non-intervention group.Children of both groups were given diet and exercise guidance, and the VD intervention group was supplemented with calcitriol 800 U/d for 16 weeks additionally. The changes of parameters were compared. Results 1) Serum 25(OH)D level of children in obesity with NAFLD group [(20.94±6.88) ng/ml] was significantly lower than that in obesity without NAFLD group [(24.31±7.69) ng/ml, P<0.05] and healthy control group [(29.19±5.44) ng/ml, P<0.01]. Serum 25(OH)D level was negatively correlated with body mass index (BMI) and HOMA-IR (r=－0.37,－0.71, P<0.01). 2) The detection rate of VD deficiency and insufficiency in obese children with NAFLD (84.48%) was higher than that in obese children without NAFLD (68.18%) and healthy control group (35.00%), and the difference was significant (χ²=25.85, P<0.01). 3) Before intervention, there was no significant difference in parameters between VD intervention group and VD non-intervention group. After 16-week intervention, compared with the VD non-intervention group, serum 25(OH)D level was significantly higher (t=2.22, P<0.05) while the levels of serum lipid, transaminase, BMI and HOMA-IR were significantly lower in VD intervention group (P<0.05). The hepatic pathology also improved after intervention. Conclusions VD deficiency is common in obese children with NAFLD. VD supplementation can effectively improve serum 25(OH)D level, attenuate liver function, hyperlipidemia, insulin resistance and fatty liver.

Key words: vitamin D, children, obesity, nonalcoholic fatty liver disease, insulin resistance

中图分类号:

蒋雪, 高健, 洪泽, 周文娣. 维生素D治疗肥胖合并非酒精性脂肪肝儿童的临床研究[J]. 中国儿童保健杂志, 2022, 30(9): 970-974.

JIANG Xue, GAO Jian, HONG Ze, ZHOU Wen-di. Clinical study on treatment of obese children with nonalcoholic fatty liver disease by vitamin D[J]. Chinese Journal of Child Health Care, 2022, 30(9): 970-974.

参考文献

[1] 周雪莲, 傅君芬. 儿童非酒精性脂肪肝病诊断与治疗专家共识[J]. 中国实用儿科杂志, 2018,33(7):487-492.
[2] Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children:Recommendations from the expert committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)[J]. J Pediatr Gastroenterol Nutr, 2017,64(2):319-334.
[3] Targher G, Byrne CD, Tilg H. NAFLD and increased risk of cardiovascular disease:Clinical associations, pathophysiological mechanisms and pharmacological implications[J]. Gut, 2020,69(9):1691-1705.
[4] Watt MJ, Miotto PM, De Nardo W, et al. The liver as an endocrine organ-linking NAFLD and insulin resistance[J]. Endocr Rev, 2019,40(5):1367-1393.
[5] Nobili V, Alisi A, Valenti L, et al. NAFLD in children:new genes, new diagnostic modalities and new drugs[J]. Nat Rev Gastroenterol Hepatol, 2019,16(9):517-530.
[6] Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease[J]. Nutrients, 2020,12(7):2097.
[7] Barchetta I, Cimini FA, Cavallo MG. Vitamin D and metabolic dysfunction-associated fatty liver disease (MAFLD):An update[J]. Nutrients, 2020,12(11):3302.
[8] Borges CC, Salles AF, Bringhenti I, et al. Vitamin D deficiency increases lipogenesis and reduces beta-oxidation in the liver of diet-induced obese mice[J]. J Nutr Sci Vitaminol (Tokyo), 2018,64(2):106-115.
[9] Zhang H, Shen Z, Lin Y, et al. Vitamin D receptor targets hepatocyte nuclear factor 4alpha and mediates protective effects of vitamin D in nonalcoholic fatty liver disease[J]. J Biol Chem, 2020,295(12):3891-3905.
[10] Tabrizi R, Moosazadeh M, Lankarani KB, et al. The effects of vitamin D supplementation on metabolic profiles and liver function in patients with non-alcoholic fatty liver disease:A systematic review and meta-analysis of randomized controlled trials[J]. Diabetes Metab Syndr, 2017,11(Suppl 2):975-982.
[11] 李辉, 季成叶, 宗心南, 等. 中国0～18岁儿童、青少年体块指数的生长曲线[J]. 中华儿科杂志, 2009,47(7):493-498.
[12] 中华医学会儿科学分会内分泌遗传代谢学组.儿童非酒精性脂肪肝病诊断与治疗专家共识[J].中华儿科杂志, 2018,33(7):487-492.
[13] 中华医学会骨质疏松和骨矿盐疾病分会. 维生素D及其类似物临床应用共识[J]. 中华骨质疏松和骨矿盐疾病杂志, 2018,11(1):1-19.
[14] Ganmaa D, Enkhmaa D, Nasantogtokh E, et al. Vitamin D, respiratory infections, and chronic disease:Review of Meta-analyses and randomized clinical trials[J]. J Intern Med, 2022,291(2):141-164.
[15] Holick MF. The vitamin D deficiency pandemic:Approaches for diagnosis, treatment and prevention[J]. Rev Endocr Metab Disord, 2017,18(2):153-165.
[16] Hu Y, Chen J, Wang R, et al. Vitamin D nutritional status and its related factors for Chinese children and adolescents in 2010—2012[J]. Nutrients, 2017,9(9):1024.
[17] 梁虹, 于立君. 肥胖和维生素D缺乏相关性的研究进展[J]. 中国儿童保健杂志, 2016,24(1):40-42.
[18] Borges CC, Salles AF, Bringhenti I, et al. Vitamin D deficiency increases lipogenesis and reduces beta-oxidation in the liver of diet-induced obese mice[J]. J Nutr Sci Vitaminol (Tokyo), 2018,64(2):106-115.
[19] Liu Y, Wang M, Xu W, et al. Active vitamin D supplementation alleviates initiation and progression of nonalcoholic fatty liver disease by repressing the p53 pathway[J]. Life Sci, 2020,241:117086.
[20] Hussain M, Iqbal J, Malik SA, et al. Effect of vitamin D supplementation on various parameters in non-alcoholic fatty liver disease patients[J]. Pak J Pharm Sci, 2019,32(3 Special):1343-1348.
[21] Mahmoudi L, Asadi S, Al-Mousavi Z, et al. A randomized controlled clinical trial comparing calcitriol versus cholecalciferol supplementation to reduce insulin resistance in patients with non-alcoholic fatty liver disease[J]. Clin Nutr, 2021,40(5):2999-3005.
[22] Barchetta I, Del BM, Angelico F, et al. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes:A randomized, double-blind, placebo-controlled trial[J]. BMC Med, 2016,14:92.
[23] Dabbaghmanesh MH, Danafar F, Eshraghian A, et al. Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease:A randomized double blind placebo controlled trial[J]. Diabetes Metab Syndr, 2018,12(4):513-517.