Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
The Children's Obesity Clinic, Accredited European Centre for Obesity Management, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
EBioMedicine. 2024 Jul;105:105205. doi: 10.1016/j.ebiom.2024.105205. Epub 2024 Jun 24.
Birth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. We aimed to determine the modifying effect of childhood obesity on these associations.
We used data from The cross-sectional HOLBAEK Study with 4263 participants (median [IQR] age, 11.7 [9.2, 14.3] years; 57.1% girls and 42.9% boys; 48.6% from an obesity clinic and 51.4% from a population-based group). We gathered information on BW and gestational age, anthropometrics, cardiometabolic risk factors, calculated a PGS for BW, and measured plasma proteins using Olink Inflammation and Cardiovascular II panels. We employed multiple linear regression to examine the associations with BW as a continuous variable and performed interaction analyses to assess the effect of childhood obesity on cardiometabolic risk and plasma protein levels.
BW and a PGS for BW associated with cardiometabolic risk and plasma protein levels in childhood and adolescence. Childhood obesity modified the associations between BW and measures of insulin resistance, including HOMA-IR (βadj [95% CI per SD] for obesity: -0.12 [-0.15, -0.08]; normal weight: -0.04 [-0.08, 0.00]; Pinteraction = 0.004), c-peptide (obesity: -0.11 [-0.14, -0.08]; normal weight: -0.02 [-0.06, 0.02]; Pinteraction = 5.05E-04), and SBP SDS (obesity: -0.12 [-0.16, -0.08]; normal weight: -0.06 [-0.11, -0.01]; Pinteraction = 0.0479). Childhood obesity also modified the associations between BW and plasma levels of 14 proteins (e.g., IL15RA, MCP1, and XCL1; Pinteraction < 0.05).
We identified associations between lower BW and adverse metabolic phenotypes, particularly insulin resistance, blood pressure, and altered plasma protein levels, which were more pronounced in children with obesity. Developing effective prevention and treatment strategies for this group is needed to reduce the risk of future CMD.
Novo Nordisk Foundation (NNF15OC0016544, NNF0064142 to T.H., NNF15OC0016692 to T.H. and A.K., NNF18CC0033668 to S.E.S, NNF18SA0034956 to C.E.F., NNF20SA0067242 to DCA, NNF18CC0034900 to NNF CBMR), The Innovation Fund Denmark (0603-00484B to T.H.), The Danish Cardiovascular Academy (DCA) and the Danish Heart Foundation (HF) (PhD2021007-DCA to P.K.R, 18-R125-A8447-22088 (HF) and 21-R149-A10071-22193 (HF) to M.A.V.L., PhD2023009-HF to L.A.H), EU Horizon (668031, 847989, 825694, 964590 to A.K.), Innovative Health Initiative (101132901 for A.K.), A.P. Møller Foundation (19-L-0366 to T.H.), The Danish National Research Foundation, Steno Diabetes Center Sjælland, and The Region Zealand and Southern Denmark Health Scientific Research Foundation.
出生体重（BW）与成年人心血管代谢疾病（CMD）的风险相关，这可能取决于肥胖的状态，尤其是在年轻时发生的肥胖。我们假设 BW 和 BW 的多基因评分（PGS）与儿童和青少年的心血管代谢风险和相关血浆蛋白水平相关。我们旨在确定儿童肥胖对这些关联的修饰作用。
我们使用来自横断面霍尔贝克研究的数据，其中包括 4263 名参与者（中位数[IQR]年龄，11.7[9.2，14.3]岁；57.1%女孩和 42.9%男孩；48.6%来自肥胖诊所，51.4%来自基于人群的组）。我们收集了 BW 和胎龄、人体测量学、心血管代谢危险因素的信息，计算了 BW 的 PGS，并使用 Olink 炎症和心血管 II 面板测量了血浆蛋白。我们采用多元线性回归来检验 BW 作为连续变量的关联，并进行了交互分析，以评估儿童肥胖对心血管代谢风险和血浆蛋白水平的影响。
BW 和 BW 的 PGS 与儿童和青少年的心血管代谢风险和血浆蛋白水平相关。儿童肥胖改变了 BW 与胰岛素抵抗指标之间的关联，包括 HOMA-IR（肥胖的βadj[95%CI 每 SD]：-0.12[-0.15，-0.08]；正常体重：-0.04[-0.08，0.00]；P 交互=0.004）、c-肽（肥胖：-0.11[-0.14，-0.08]；正常体重：-0.02[-0.06，0.02]；P 交互=5.05E-04）和 SBP SDS（肥胖：-0.12[-0.16，-0.08]；正常体重：-0.06[-0.11，-0.01]；P 交互=0.0479）。儿童肥胖也改变了 BW 与 14 种血浆蛋白水平之间的关联（例如，IL15RA、MCP1 和 XCL1；P 交互<0.05）。
我们发现 BW 较低与代谢不良表型，特别是胰岛素抵抗、血压和血浆蛋白水平改变相关，在肥胖儿童中更为明显。需要制定有效的预防和治疗策略来治疗该人群，以降低未来 CMD 的风险。
诺和诺德基金会（NNF15OC0016544、NNF0064142 给 T.H.、NNF18CC0033668 给 S.E.S.、NNF18SA0034956 给 C.E.F.、NNF20SA0067242 给 DCA、NNF18CC0034900 给 NNF CBMR）、丹麦创新基金会（0603-00484B 给 T.H.）、丹麦心血管学院（DCA）和丹麦心脏基金会（HF）（PhD2021007-DCA 给 P.K.R.、18-R125-A8447-22088 （HF）和 21-R149-A10071-22193 （HF）给 M.A.V.L.、PhD2023009-HF 给 L.A.H.）、欧盟地平线（668031、847989、825694、964590 给 A.K.）、创新健康倡议（101132901 给 A.K.）、A.P. 莫勒基金会（19-L-0366 给 T.H.）、丹麦国家研究基金会、Steno 糖尿病中心 Zealand 和南丹麦健康科学研究基金会。
