Insulin Resistance In Prepubertal Children Research Articles

Circulating microRNA levels differ in the early stages of insulin resistance in prepubertal children with obesity

AimsThe increasing prevalence of childhood obesity escalates the risk for related complications. Circulating microRNAs (miRNAs) have been suggested as good predictive markers of insulin resistance in those with obesity. The aim was to identify a circulating miRNA profile that reflects insulin resistance in prepubertal children with obesity. Material and methodsPlasma miRNAs were measured in prepubertal children (n = 63, 5–9 years) using TaqMan Advanced miRNA Human Serum/Plasma plates and then were validated by RT-qPCR. Subjects were divided into normal weight (n = 20, NW) and overweight or obese (n = 43, OW/OB) groups according to their BMI z-scores. The OW/OB group was further subdivided into insulin sensitive or metabolically healthy obese (n = 26, MHO) and insulin resistant or metabolically unhealthy obese (n = 17, MUO) according to HOMA-IR. Key findingsWhile no differences were observed in the fasting plasma glucose levels, serum insulin levels were significantly elevated in the OW/OB compared to the NW group. Of 188 screened miRNAs, eleven were differentially expressed between the NW and OW/OB groups. Validation confirmed increased circulating levels of miR-146a-5p and miR-18a-5p in the OW/OB group, which correlated with BMI z-score. Interestingly, miR-146a-5p was also correlated with HOMA-IR index. While only miR-18a-5p was upregulated in the OW/OB children, independently of their degree of insulin sensitivity, miR-146-5p, miR-423-3p and miR-152-3p were associated with insulin resistance. SignificanceThe present study provides evidence of molecular alterations that occur early in life in prepubertal obesity. These alterations may potentially be crucial for targeted prevention or prompt precision therapeutic development and subsequent interventions.

Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

Psoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3–10 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was ≥ 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance.Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis.What is Known:• Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.• Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis.What is New:• This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.• In children with psoriasis metabolic syndrome risk factors should be assessed.

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity.

SummaryObjectivesS100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined.MethodsSixty‐five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty‐nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine.ResultsCirculating S100A4 levels were increased in both children (P = .002) and adults (P < .001) with obesity compared with their normal‐weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment‐insulin resistance (HOMA‐IR) in adults (βstd = .42, P = .008) but not in children (βstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC.ConclusionsOur human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti‐inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity.

Insulin Resistence in Obese and Non Obese Pre-Pubertal Children:Cross Sectional Study in Indonesia

High prevalence of childhood obesity increases risk of insulin resistance in pre-pubertal children. The purpose of this study is to identify the presence of insulin resistance in pre-pubertal obese children and compare with children who had normal nutritional status. Observational analytic study with a cross sectional design is used for this research. There are 60 elementary school students aged 6-9 years involved in this study, 30 obese students and 30 students with normal nutritional status based on BMI for Age. Fasting insulin, fasting blood glucose and HOMA IR index were carried out in Parahita Laboratory at Sidoarjo. Statistical analysis using independent t-test was used to determine differences in fasting blood glucose, fasting insulin and HOMA IR between two groups and linear regression to analyze the effect of obesity on insulin resistance with a significance value &lt; 0.05.The results showed mean scores of BMI obese and non-obese group were 25.6 and 15.96 respectively, the mean value of BMI z score among obese group and non-obese was 3.7 and-0.6 respectively; the abdominal circumference value of obese and non obese group consist of 84.95 and 59.48 cm. Statistical analysis showed no significant difference in fasting blood glucose levels, but fasting insulin levels and HOMA IR between 2 groups differed significantly. Obesity (BMI and abdominal circumference) influenced incidence of insulin resistance. Furthermore, obese and non-obese groups have different sensitivity of insulin response but had the same blood glucose level; obese group had higher HOMAIR than non-obese group. So, there needs an intervention to reduce obesity at an early age to reduce the risk of insulin resistance in pre-pubertal age.

Towards a simple marker of hepato‐visceral adiposity and insulin resistance: The Z‐score change from weight‐at‐birth to BMI‐in‐childhood

Insulin resistance and hepato-visceral (central) fat excess are thought to contribute to an earlier timing of adrenarche/pubarche and puberty/menarche; this earlier timing in turn relates often to a mismatch between prenatal and postnatal weight gain, which can be estimated by calculating the Z-score change from birth weight (BW) to body mass index (BMI) in childhood. We tested the hypothesis that this calculation may serve as a proxy of insulin resistance and hepato-visceral adiposity in prepuberty by reappraising a cohort of children (mean age, 8.5years), born appropriate- (AGA, n=41) or small-for-gestational age (SGA, n=45), followed since birth (n=76) or since the age of 3 years (n=10). Assessments included anthropometry; fasting glucose and insulin; liver volume; and hepatic fat, subcutaneous fat, and visceral fat in the abdominal region (by magnetic resonance imaging [MRI]). Z-score change BW-BMI closely associated to central fat (R=0.74; P<.0001) and insulin resistance (R=0.71; P<.0001). These results suggest that Z-score change BW-BMI could be viewed as a simple candidate-marker for hepato-visceral adiposity and insulin resistance in prepubertal children.

Insulin Resistance in Prepubertal Children in Relation to Intrauterine Exposure to Overnutrition

Background and aims: Intrauterine factors contributing to fetal overnutrition have been associated with greater insulin resistance in neonates, however it is unknown whether this persists into childhood.

Elevated circulating levels of the serum acute-phase protein YKL-40 (chitinase 3-like protein 1) are a marker of obesity and insulin resistance in prepubertal children

YKL-40 (chitinase 3-like protein 1) is a newly recognized protein that is secreted by activated macrophages and neutrophils and expressed in a broad spectrum of inflammatory conditions and cancers. It has also been associated with endothelial dysfunction and diabetes in adults. Its role in childhood obesity has not been evaluated yet. Our aim was to evaluate the associations of serum YKL-40 levels with markers of obesity, inflammation, and insulin resistance in children. Forty-one obese prepubertal children and 41 age- and sex-matched lean controls were included, and serum YKL-40 levels were determined. Body mass index (BMI), blood pressure (BP), body fat percentage, fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR) index, whole-body insulin sensitivity index, lipids, white blood cell (WBC) count, C-reactive protein, and fibrinogen levels were also assessed. Obese children had higher YKL-40 levels compared with controls (P = .003). Insulin-resistant individuals showed higher YKL-40 compared with non–insulin-resistant individuals after adjusting for age and BMI (adjusted P = .039). Serum YKL-40 levels were positively correlated with age, BMI, body fat percentage, fasting glucose and insulin, HOMA-IR index, whole-body insulin sensitivity index, systolic BP, mean BP, and WBC count (P < .05). After adjustment for age, sex, BMI, WBC count, and systolic BP, HOMA-IR index remained significantly associated with YKL-40 levels (P < .001). The study suggests that YKL-40 levels are elevated in obese youth and represent a marker of insulin resistance even in childhood. Prospective studies are needed to determine whether children with elevated YKL-40 levels are at higher risk for future cardiovascular disease.

Retinol-binding protein 4 correlates with triglycerides but not insulin resistance in prepubertal children with and without premature adrenarche

Retinol-binding protein 4 (RBP4) has been proposed as an early marker for insulin resistance (IR), but no prior studies have addressed RBP4 in an exclusively prepubertal population. Children with premature adrenarche (PA) are at increased risk for IR and metabolic syndrome (MeS); thus finding an appropriate early marker for IR in this population would allow for early intervention and prevention of morbidity related to IR and MeS. To determine whether prepubertal children with PA have higher levels of RBP4 than controls and whether RBP4 correlates with comorbidities of metabolic disease in prepubertal children. This study comprised 49 prepubertal children (24 with PA and 25 control subjects), 20 boys and 29 girls, who were between the ages of 5 and 9 years. This was a cross-sectional, case-control study conducted in a subspecialty ambulatory clinic based in a quaternary care center. RBP4 levels, hormonal values, lipids, and response to an oral glucose tolerance test were evaluated in children with PA and controls, and body composition measures were obtained in a subset of patients (n = 18). RBP4 correlated with triglycerides (r = 0.57, p < 0.0001) but did not correlate with IR in a body mass index z-score-adjusted Pearson correlation analysis. There was no difference in RBP4 levels between the PA and control groups. These findings suggest that RBP4 may be an early marker of dyslipidemia, which may herald future onset of hepatic IR, polycystic ovary syndrome, and MeS.

The role of metabolic syndrome components and adipokines in insulin resistance in prepubertal children

Insulin resistance has a central role in the pathophysiology of cardiovascular atherosclerotic disease. Adipose tissue is of capital importance in view of its production of adipokines. The present study aims to determine the association of metabolic syndrome components, which constitute risk factors for cardiovascular atherosclerotic disease, and leptin and adiponectin with insulin resistance in prepubertal children. We conducted a cross-sectional study involving 197 children. Of these, 112 children were obese, 36 were overweight and 49 had normal weight. The association of sex, waist circumference, Acanthosis nigricans, age, BMI Z-score, serum lipids, leptin and adipocytokines with insulin resistance [defined as the homeostatic model assessment for insulin resistance (HOMA-IR) index higher than or equal to 2.5] was investigated using logistic regression. There was positive association of sex (female), age, BMI Z-score, triglycerides and leptin with insulin resistance (p<0.05). Among the conventional components of metabolic syndrome, the role of BMI Z-score and triglycerides stands out in insulin resistance of prepubertal children. Sex (female), age and leptin also showed to be of major importance.

Intrahepatic and intramyocellular lipids are determinants of insulin resistance in prepubertal children

We hypothesised that ectopic fat deposition is present in liver and skeletal muscle before puberty and that both are potentially important factors in the early pathogenesis of insulin resistance. Proton magnetic resonance spectroscopy was used to evaluate intramyocellular and intrahepatic lipids in 50 male and 42 female multi-ethnic, prepubertal (Tanner < 2) children (8.1 ± 0.8 years; 35.4 ± 10.7 kg; 27.9 ± 8.3% body fat; means ± SD). Intramyocellular lipid was measured in soleus muscle and intrahepatic lipid in the middle right lobe. Abdominal fat was measured by magnetic resonance imaging, body fat by dual energy X-ray absorptiometry, and insulin resistance using homeostatic model assessment. Intrahepatic lipid ranged from 0.11% to 4.6% relative to the liver water signal (mean 0.79 ± 0.79%) whereas intramyocellular lipid ranged from 0.13% to 1.86% relative to the muscle water signal (mean 0.51 ± 0.28%). Intramyocellular and intrahepatic lipids were significantly correlated with total adiposity (r = 0.49 and 0.59), abdominal adiposity (r = 0.44 and 0.54), and each other (r = 0.39, p < 0.05, Spearman). Both intramyocellular and intrahepatic lipid were positively correlated with fasting insulin (r = 0.37 and 0.38 respectively) and insulin resistance (r = 0.37 and 0.37; p < 0.01). After adjustment for race and sex, the relations between ectopic fat and insulin resistance remained, whereas both disappeared when further adjusted for body fat or BMI z scores. These results suggest that typical relations between body composition, ectopic fat and insulin resistance are present in children before puberty. Thus, interventions aimed at reducing adiposity have the potential to decrease ectopic fat accumulation, delay the onset of insulin resistance and decrease the risk for development of type 2 diabetes in children.

The Influence of Fat Mass and Physical Activity on Insulin Resistance in Prepubertal Youth

Recent studies have investigated the relationship of fat mass (FM) and physical activity (PA) levels on insulin resistance (IR) in adolescents; however few studies have examined this effect in prepubertal youth. PURPOSE: To examine the relationship of PA and FM to IR in a bi-ethnic sample of 7-9 year old prepubertal youth (n = 20; M = 10, F = 10; Caucasian = 14, African American and other = 6; 7.85 ± 0.67 yrs. [mean ± SD]). METHODS: Fat mass was measured by DEXA, PA by accelerometry (GT1M ActiGraph), and IR was calculated by Homeostasis Model Assessment (HOMA).Figure: Caption not available.RESULTS: We observed a moderate, non-significant correlation (r = 0.42, p=0.20) between PA and IR and a strong, significant correlation (r = 0.86, p<0.001) between FM and IR. CONCLUSION: Increased amounts of total FM were strongly associated with increased IR in this sample of prepubertal youth. The results from this investigation confirm those of others and suggest that increased FM contributes to insulin resistance in prepubertal children and thus serves as a potential risk factor for the development of type II diabetes later in adolescence or adulthood. Supported by National Institute of Child Health & Human Development (HD41071; 41076), National Institutes of Health, USA

Trends, associations and predictions of insulin resistance in prepubertal children (EarlyBird 29)

Rising obesity has been observed in all age groups. Anthropometric cut-points have been used to predict metabolic risk in children, although they are not based on known outcomes. We examined the trends, associations and predictions of metabolic health from anthropometry in prepubertal children. Three hundred and seven healthy children were examined annually between 5 and 8 yr. height, weight, body mass index (BMI), sum of skinfold thickness at five sites (SSF) and waist circumference (WC). homeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Two hundred and thirty-one [131 boys (B) and 100 girls (G)] children had complete data sets at all four time points. (i) All measures of adiposity rose from 5 to 8 yr (BMI - B: +3.4%, G: +5.7%; WC - B: +10.4%, G: +11.8%; SSF - B: +23.3%, G: +30.7%, all p < 0.001). HOMA-IR unexpectedly fell (B: -16.6%, p = 0.01; G: -32.5%, p < 0.001). This fall was significant between 5 and 6 yr in both genders (5-6 yr - B: -17.8%, p < 0.001; G: -20.0%, p = 0.002) and between 6 and 7 yr in girls only (6-7 yr - B: -10.8%, p = 0.12; G: -19.2%, p = 0.001). HDL-C rose (B: +17.8%, G: +17.1%, both p < 0.001) and TG fell (B: -4.8%, p = 0.16; G: -11.6%, p = 0.006). (ii) Correlations between insulin resistance (IR) and anthropometry were poor at 5 yr but strengthened by 8 yr (BMI - B: r = 0.20/0.38, G: r = 0.28/0.49; WC - B: r = 0.25/0.40, G: r = 0.32/0.58; SSF - B: r = 0.11/0.36, G: r = 0.18/0.53). (iii) In girls, but not boys, adiposity at 5 yr predicted IR better at 8 yr (BMI - r(2 )= 0.17; WC - r(2 )= 0.28; SSF - r(2 )= 0.17, all p < 0.001) than it did at 5 yr (BMI - r(2 )= 0.08, p < 0.01; WC - r(2 )= 0.10, p < 0.01; SSF - r(2 )= 0.03, p = 0.07). Cross-sectional association cannot indicate direction of trend or predict the future. Predicting metabolic health from anthropometric measures in prepubertal children requires longitudinal data, tracking variables from childhood into adulthood. Until the data set reaches adulthood, it is probably not safe to make recommendations on which children to 'target' or whether early intervention would be of benefit.

Influence of family history of type 2 diabetes on insulin sensitivity in prepubertal children.

The objective of this study was to examine the influence of positive family history (FH) of type 2 diabetes (T2D) on aspects of insulin resistance in prepubertal children. Twenty-one children (Tanner stage I or II) with a positive FH were compared with children with no FH. FH was defined by presence of T2D in a parent or grandparent as assessed by interview. The two groups of children were matched for age, gender, Tanner stage, ethnicity, geographical location, and body fat mass using a pair-matched design. These 21 pairs of children included Caucasian, African American, and Hispanic children who were studied either in Birmingham, Alabama, or Los Angeles, California, using similar techniques. Insulin sensitivity (S(I)) and the acute insulin response to glucose (AIR) were determined by an iv glucose tolerance test and minimal modeling, and body composition was determined by dual-energy x-ray absorptiometry. There were no significant differences in fasting glucose or insulin, S(I), AIR, the disposition index (product of S(I) and AIR), or body composition between children with a FH vs. those without a FH of T2D, and there were no significant differences in these parameters when the data were analyzed separately in each ethnic group. In conclusion, a positive FH for T2D does not seem to have any significant effect on insulin sensitivity, as assessed by the minimal model and associated risk factors for T2D in young children.