The Vitamin D Decrease in Children with Obesity Is Associated with the Development of Insulin Resistance during Puberty: The PUBMEP Study

Pires, Liliane Viana; González-Gil, Esther M.; Anguita‐Ruiz, Augusto; Bueno, Gloria; Gil-Campos, Mercedes; Vázquez-Cobela, Rocío; Pérez-Ferreirós, Alexandra; Moreno, Luís A.; Gil, Ángel; Leis, Rosaura; Aguilera, Concepción M.

doi:10.3390/nu13124488

Cited by 9 publications

(11 citation statements)

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“…This study was conducted within the context of the multicenter PUBMEP study in Spain “Puberty and metabolic risk in children with obesity”, previously published [9, 10]. Here, a sub-population of 119 pubertal children (54 boys and 65 girls) from the whole PUBMEP cohort was selected for analysis.…”

Section: Methodsmentioning

confidence: 99%

Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

Ruiz‐Ojeda

Anguita‐Ruiz

Rico

et al. 2022

Preprint

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Purpose: The aims of this study were; 1) to evaluate if there is an association between the serum levels of the novel insulin-like adipokine isthmin-1 (ISM1) and obesity-related phenotypes in a population of Spanish children, 2) to investigate the plausible molecular alterations behind the alteration of the serum levels of this protein in children with obesity. Methods: The study population is a sub-cohort of the PUBMEP research project, consisting of a cross-sectional population of 119 pubertal children with overweight (17 boys, 19 girls), obesity (20 boys, 25 girls) and normal weight (17 boys, 21 girls). All subjects were classified into experimental groups according to their sex, obesity and insulin resistance (IR) status. They counted on anthropometry, glucose, and lipid metabolism, inflammation and cardiovascular biomarkers as well as ISM1 serum levels measured. This population was intended as a discovery population in which to elucidate the relationship between obesity and ISM1 levels in children. Furthermore, the study population had blood whole-genome DNA methylation allowing deepening into the obesity-ISM1 molecular relationship. Results: Higher serum levels of ISM1 were observed in boys with obesity when compared with normal-weight (P=0.004), and overweight (P=0.007). ISM1 serum levels were positively associated with BMI Z-score (P=0.005), and negatively with myeloperoxidase (MPO) (p=0.043) in boys. Nevertheless, we did not find associations between ISM1 serum levels and metabolic outcomes in girls, indicating a putative sexual dimorphism. DNA methylation levels in two-enhancer-related CpG sites of ISM1 (cg03304641 and cg14269097) were associated with serum levels of ISM1 in children. Discussion: We report an unprecedented study that provides a major step forward showing that ISM1 is robustly associated with obesity in pubertal boys, elucidating how this protein might be of special relevance as a new biomarker of obesity in children.

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Section: Methodsmentioning

confidence: 99%

Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

Ruiz‐Ojeda

Anguita‐Ruiz

Rico

et al. 2022

Preprint

Self Cite

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“…Obesity-related insulin resistance and low-grade chronic inflammation seem to be the most important predictive factors for the development of complications of overweight and obesity such as metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and osteopenia/osteoporosis ( 47 ). The associations between vitamin D status and insulin sensitivity parameters in obese pediatric population have been previously reported ( 12 , 48 – 53 ). The effects of vitamin D on glucose homeostasis, exerted mainly by its active form 1,25-dihydroxycholecalciferol, include the increase of peripheral and hepatic glucose uptake, the improvement in synthesis and secretion of insulin, the protection of β-cells from cytokine induced apoptosis and attenuation of inflammation ( 47 , 54 – 56 ).…”

Section: Discussionmentioning

confidence: 77%

“…( 62 ), among a group of more than one hundred obese children with 25(OH)D levels above or below 20 ng/ml, found higher total cholesterol and LDL-C levels in the group with vitamin D deficit. It should be noted that the stage of puberty also affects the relationship between vitamin D and the components of metabolic syndrome in obese children ( 53 , 70 , 71 ). Pires et al.…”

Section: Discussionmentioning

confidence: 99%

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The link between vitamin D, chemerin and metabolic profile in overweight and obese children - preliminary results

et al. 2023

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BackgroundVitamin D affects adipogenesis, oxidative stress, inflammation, secretion of adipocytokines, lipid metabolism and thermogenesis. Some researchers postulate that those effects could be exerted by the influence of vitamin D on chemerin levels.Aim of the studyWe aimed to investigate if there is a link between serum 25-hydroksyvitamin D [25(OH)D], chemerin and metabolic profile in overweight and obese children before and after vitamin D supplementation.Material and methodsThe prospective study included 65 overweight and obese children aged 9.08-17.5 years and 26 peers as a control. None of the patients in the study group had received vitamin D within the last twelve months before the study.ResultsThe study group had lower baseline 25(OH)D (p<0.001) and higher chemerin (p<0.001), triglycerides (TG, p<0.001), triglycerides/high density lipoprotein cholesterol (TG/HDL-C, p<0.001), C-reactive protein (CRP, p<0.05), fasting insulin (p<0.001), Homeostasis Model Assessment - Insulin Resistance (HOMA-IR, p<0.001), alanine aminotransferase (ALT, p<0.001) and uric acid (p<0.001) compared to the control group. Baseline vitamin D was related to fasting insulin (R=-0.29, p=0.021), HOMA-IR (R=-0.30, p=0.016), HDL-C (R=0.29, p=0.020) and uric acid (R=-0.28, p=0.037) in the study group. Baseline chemerin was related to insulin at 30’ (R=0.27, p=0.030), 60’ (R=0.27, p=0.033), 90’ (R=0.26, p=0.037) and 120’ (R=0.26, p=0.040) during the oral glucose tolerance test (OGTT) and ALT (R=0.25, p=0.041) in the study group. Correlation between vitamin D and chemerin (R=-0.39, p=0.046) was found only in the control group. After six months of vitamin D supplementation a decrease in CRP (p<0.01), total cholesterol (p<0.05), ALT (p<0.01), glucose at 150’ OGTT (p<0.05) was observed. Moreover, we noticed a tendency for negative association between 25(OH)D and chemerin levels (p=0.085). Multivariable backward linear regression models were build using baseline vitamin D, baseline chemerin and six months chemerin as the dependent variables.ConclusionsOur study confirmed that vitamin D has positive effect on metabolic profile in overweight and obese children. The relationship between vitamin D and chemerin is not clear, nevertheless we have observed a tendency to decrease chemerin concentrations after improving vitamin D status, even without a significant reduction in body fat mass.

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“…An adequate 1,25-dihydroxyvitamin D3 level is essential for normal insulin secretion[ 44 , 45 ]. Pires et al [ 46 ] showed that vitamin D deficiency in children with overweight or obesity increases the risk of IR during puberty.…”

Section: Risk Factors For Irmentioning

confidence: 99%

Insulin-resistance in paediatric age: Its magnitude and implications

Al‐Biltagi¹,

Bediwy²,

Saeed³

2022

WJD

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Insulin resistance (IR) is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues. IR is becoming more common in children and adolescents than before. There is a strong association between obesity in children and adolescents, IR, and the metabolic syndrome components. IR shows marked variation among different races, crucial to understanding the possible cardiovascular risk, specifically in high-risk races or ethnic groups. Genetic causes of IR include insulin receptor mutations, mutations that stimulate autoantibody production against insulin receptors, or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules; all induce abnormal energy pathways and end with the development of IR. The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR. Most patients with IR do not develop diabetes mellitus (DM) type-II. However, IR is a crucial risk factor to develop DM type-II in children. Diagnostic standards for IR in children are not yet established due to various causes. Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test. Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance. The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR, enhance insulin sensitivity, and treat possible complications. There are three main lines for treatment: Lifestyle and behavior modification, pharmacotherapy, and surgery. This review will discuss the magnitude, implications, diagnosis, and treatment of IR in children.

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The Vitamin D Decrease in Children with Obesity Is Associated with the Development of Insulin Resistance during Puberty: The PUBMEP Study

Cited by 9 publications

References 58 publications

Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

The link between vitamin D, chemerin and metabolic profile in overweight and obese children - preliminary results

Insulin-resistance in paediatric age: Its magnitude and implications

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