Insulin Resistance In Boys Research Articles

The CCR2+ Monocyte Subsets Increase in Obese Boys but Not Girls with Abnormally High Carotid Intima-Media Thickness: A Pilot Study.

The differential contribution of monocyte subsets expressing the C-C chemokine receptor 2 (CCR2) to subclinical atherosclerosis in girls and boys is unclear. In this pilot study, we compared classical, intermediate, and nonclassical monocyte subsets expressing CCR2 in 33 obese children of both sexes aged 8 to 16 divided by carotid intima-media thickness (IMT), considering values above the 75th percentile (p75) as abnormally high IMT. Obesity was defined as body mass index above the 95th percentile according to age and sex. Flow cytometry analyses revealed that boys but not girls with IMT ≥ p75 displayed increased CCR2+ cell percentage and CCR2 expression in the three monocyte subsets, compared to boys with IMT < p75. The CCR2+ cell percentage and CCR2 expression in the three monocyte subsets significantly correlated with increased IMT and insulin resistance in boys but not girls, where the CCR2+ nonclassical monocyte percentage had the strongest associations (r = 0.73 and r = 0.72, respectively). The role of CCR2+ monocyte subpopulations in identifying an abnormally high IMT shows a marked sexual dimorphism, where boys seem to be at higher subclinical atherosclerosis risk than girls.

Особливості ендокринного статусу в дітей з ожирінням та поліморфізмами гена лактази

Актуальність. Ожиріння — це дисбаланс імуноцитокінової та нейроендокринної регуляції енергетичного обміну з надлишковим накопиченням жирової тканини в організмі, пов’язаний з формуванням хронічної прозапальної імунної відповіді, асоційованої з генотипом С/С 13910 гена лактази. Мета дослідження: визначити особливості тиреоїдного, статевого гормонального статусу, жирового обміну та формування лептинорезистентності в дітей з ожирінням та поліморфізмами (SNP) гена лактази (LCT). Матеріали та методи. Проведено комплексне обстеження згідно з діючим протоколом зі спеціальності «дитяча ендокринологія» 76 дітей віком 6–18 років з ожирінням та SNP LCT. Першу групу (n = 36) становили діти з генотипом С/С 13910, що асоціюється з лактазною недостатністю дорослого типу. До другої групи (n = 40) увійшли фенотипово схожі діти з генотипами С/Т та Т/Т 13910, що асоціюються з лактазною персистенцією. Визначення порушень жирового обміну проводили методом біоімпедансометрії на електронних вагах Tefal Bodysignal (Франція). Дослідження ендокринного статусу виконували за допомогою імунохімічного методу тестування з електрохемілюмінісцентною детекцією (ECLIA), генотипування гену лактази — за допомогою полімеразної ланцюгової реакції в режимі реального часу. Результати. У дітей з генотипом С/С 13910 виявляються статистично значимі відмінності в ендокринному статусі, пов’язані з підвищенням інсулінорезистентності у хлопчиків до 6,79 ± 1,12 за індексом НОМА проти 3,29 ± 0,99 у хлопчиків з генотипами С/Т та Т/Т 13910 при р = 0,028. У дівчаток з генотипом С/С 13910 відмічається відносне, в межах фізіологічної норми, зниження вільного естрадіолу до 40,10 ± 0,05 пг/мл порівняно з рівнем у дівчаток з генотипами С/Т та Т/Т 13910 — 75,61 ± 4,6 пг/мл при р &lt; 0,01, з одночасним патологічним підвищенням в 3,5 раза дегідроепіандростерону сульфату у віці 15–18 років до 594,50 ± 8,81 мкг/дл відносно рівня у дівчаток з генотипами С/Т та Т/Т 13910 — 167,06 ± 12,80 мкг/дл при р &lt; 0,01. Для дівчаток з генотипом С/С 13910 характерне статистично значиме (р &lt; 0,05) підвищення рівня лептину до 47,84 ± 4,40 нг/мл порівняно з дівчатками з генотипами С/Т та Т/Т 13910 — 32,54 ± 4,30 нг/мл. Порушення жирового обміну асоціюються з більш високим рівнем жирової маси тіла (ЖМТ) у хлопчиків та дівчат з генотипом С/С 13910 відносно дітей з генотипами С/Т та Т/Т 13910, а саме: у хлопчиків з генотипом С/С 13910 середній рівень ЖМТ становив 35,46 ± 2,52 %, тоді як у хлопчиків з генотипами С/Т та Т/Т 13910 — 25,04 ± 2,14 %. У дівчаток з генотипом С/С 13910 середній рівень ЖМТ становив 38,19 ± 2,25 %, тоді як у дівчат з генотипами С/T та Т/Т 13910 середній рівень ЖМТ — 28,99 ± 0,76 % при р &lt; 0,001. Висновки. Фактором ризику ожиріння в дітей є генотип С/С 13910 гена лактази, що асоціюється з лактазною недостатністю дорослого типу. Хлопчики 6–18 років, хворі на ожиріння, носії даного генотипу, мають в 1,5 раза вищий ризик формування інсулінорезистентності. Дівчата 15–18 років з генотипом С/С 13910, хворі на ожиріння, мають в 1,5 раза вищий ризик виникнення лептинорезистентності та в 3,5 раза вищий ризик інвертованого перебігу пубертатного періоду за рахунок гіперандрогенії надниркового генезу.

Effects of X-chromosome Tenomodulin Genetic Variants on Obesity in a Children\u2019s Cohort and Implications of the Gene in Adipocyte Metabolism

Tenomodulin (TNMD) is a type II transmembrane glycoprotein that has been recently linked to obesity, and it is highly expressed in obese adipose tissue. Several sex-dependent associations have been observed between single-nucleotide polymorphisms (SNPs) of the TNMD gene, which is located in the X-chromosome, and obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome in adults. On the other hand, results are lacking for children. We aimed (i) to study the association between TNMD genetic variants and metabolic complications related to childhood obesity and (ii) to investigate the function of TNMD in human adipocytes. We conducted a case-control, multicenter study in 915 Spanish children and demonstrated significant positive associations between TNMD genetic variants and BMI z-score, waist circumference, fasting glucose, and insulin resistance in boys, highlighting the SNP rs4828038. Additionally, we showed a BMI-adjusted inverse association with waist circumference in girls. Second, in vitro experiments revealed that TNMD is involved in adipogenesis, along with glucose and lipid metabolism in differentiated adipocytes, and these effects may be mediated through AMPK activation. Hence, these results suggest that TNMD genetic variants could be potentially useful as early life risk indicators for obesity and T2DM. In addition, we support the fact that TNMD exhibits significant metabolic functions in adipocytes.

Dietary behaviors throughout childhood are associated with adiposity and estimated insulin resistance in early adolescence: a longitudinal study

BackgroundDespite the growing prevalence of excess weight and prediabetes in children, the contributing role of dietary behaviors throughout childhood remains poorly understood. We examined longitudinal associations of dietary behaviors throughout childhood with adiposity and estimated insulin resistance (HOMA-IR) in adolescence.MethodsAmong 995 children from Project Viva, a pre-birth cohort, we examined associations of child dietary behaviors (frequency of eating breakfast, fast food, family dinner, and eating meals while watching television) reported annually throughout childhood (from ages 4 to 11 years) with body mass index z-score (BMI-z; n = 991), waist circumference (WC; n = 995), DXA overall and central adiposity measurements (n = 721), and HOMA-IR (n = 579) in early adolescence (13.2 ± 0.9 years old). We used mixed effects models adjusted for potential confounders.ResultsEating breakfast daily throughout childhood was associated with lower BMI-z and DXA-measured overall and central adiposity in boys and girls (e.g. for whole-body fat %: β − 1.43% [95% CI: -2.42, − 0.45] and − 1.47% [− 2.25, − 0.68]), and with lower HOMA-IR in boys (% difference − 15.6% [− 22.7, − 7.9]). Daily family dinner and eating fast food less than once per week throughout childhood were both associated with lower BMI-z and adiposity in girls (for BMI-z: β − 0.17 units [− 0.24, − 0.11] and β − 0.09 units [− 0.17, − 0.02]) and lower insulin resistance in boys (% difference − 7.3% [− 12.4,− 1.8] and − 7.6% [− 13.2, − 1.7]). Finally, eating meals while watching television < 1/week throughout childhood was associated with lower adolescent adiposity (e.g. WC: − 1.55 cm [− 2.39, − 0.71]) and HOMA-IR (% difference: − 10.7% [− 15.8, − 5.2]) in boys.ConclusionHealthful dietary behaviors throughout childhood are associated with less adiposity and lower estimated insulin resistance in early adolescence.Trial registrationNCT02820402

Evidence of muscle loss delay and improvement of hyperinsulinemia and insulin resistance in Duchenne muscular dystrophy supplemented with omega-3 fatty acids: A randomized study

Duchenne Muscular Dystrophy (DMD) is the most prevalent dystrophy of childhood and is characterized by generalized motor delays due to progressive muscular weakness, leading to loss of muscle mass. Additionally, patients with DMD develop obesity, hyperinsulinemia, and Insulin Resistance (IR). Omega-3 Long-Chain PolyUnsaturated Fatty Acids (Ω-3LCPUFA) increase fat mass, decrease lean mass, and decrease hyperinsulinemia and IR. The aim of this study was to analyze the impact of Ω-3LCPUFA consumption on lean mass, fat mass, hyperinsulinemia, and IR in children with DMD. This placebo-controlled, double-blind, randomized study was carried out in 28 patients with DMD supplemented with 2.9g/d of Ω-3LCPUFA (n=14) or sunflower oil (placebo, n=14) during 6 months. Serum glucose and insulin were measured at baseline and thereafter at months 3 and 6 of the intervention to estimate IR by HOmeostasis Model Assessment. Body composition was assessed by Dual Energy X-ray Absorptiometry. The percentage of change in EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes was significantly (p<0.05) higher in boys who consumed Ω-3LCPUFA than in the placebo group. Lean mass and fat mass (both in g/kg of Body Weight [BW]) had a trend toward being higher (p=0.07 at month 3 and p=0.085 at month 6) and lower (p=0.05 at month 3 and p=0.085 at month 6) respectively, in boys with DMD supplemented with Ω-3LCPUFA compared with the placebo group. The loss of lean mass was delayed in the Ω-3LCPUFA group; it started at month 6 but, in placebo, it started at month 3 of supplementation in comparison with the baseline of each group. Fasting insulin, percentage of boys with hyperinsulinemia, and IR were similar between the placebo and Ω-3LCPUFA groups during the 6 months of supplementation. The percentage of boys with IR was significantly (p=0.045) lower at month 6 of supplementation in the Ω-3LCPUFA group than in the placebo group. This study suggests that Ω-3LCPUFA (2.9g/day) intake during 6 months likely slows the progression of muscle loss, decreases the fat mass, and reduces IR in boys with DMD. The findings of this study provide scientific background for conducting a randomized trial focused of confirming the possible beneficial role of Ω-3LCPUFA on the previously mentioned alterations mentioned in boys with early muscle damage (without fibrosis) DMD. This research was registered at clinicaltrials.gov (NCT018264229).

Upper Normal Alanine Aminotransferase Range and Insulin Resistance in Korean Adolescents: Korean National Health and Nutrition Examination Survey, 2009–2010

Alanine aminotransferase (ALT) has been one of the most useful biomarkers reflecting liver damage. Some studies have proposed that serum ALT levels, even those within the conventional normal range, are associated with metabolic syndrome and fatty liver. We examined the correlation between ALT levels and insulin resistance (IR) and ALT cutoff value for high IR status in Korean adolescents. A total of 886 subjects (461 boys and 425 girls) who participated in the 2009-2010 Korea National Health and Nutrition Examination Survey were included in this study. Multivariable adjusted logistic regression analyses were used to examine the odds ratios and 95% confidence intervals (CIs) of the prevalence of the highest quartile of the homeostasis model assessment of IR (HOMA-IR) according to the ALT quartile. The cutoff value of ALT for the highest HOMA-IR quartile (Q4) were obtained using receiver operating characteristic curve analysis. The mean ALT value increased as the number of metabolic syndrome components increased, but in only boys (p for trend <0.001), while the IR quartile increased in both boys and girls (all p for trends <0.001). The prevalence of IR (Q4) was only increased in ALT (Q4) in boys after the adjustment for age, body mass index, and waist circumference (OR 2.49; 95% CI 1.05-5.91; p for trend=0.017). The cutoff values were 17.0IU/L in boys and 11.0IU/L in girls. The highest ALT quartile was associated with an increased prevalence of the highest quartile of IR in boys but not in girls.

Do changes in physical activity, fitness, adiposity or diet influence insulin resistance in boys and girls? The LOOK study

Do changes in physical activity, fitness, adiposity or diet influence insulin resistance in boys and girls? The LOOK study

Prepubertal insulin resistance

Prepubertal insulin resistance

Acylation stimulating protein but not complement C3 associates with metabolic syndrome components in Chinese children and adolescents

Childhood obesity is increasing worldwide and is increasingly associated with metabolic syndrome (MetS). Our aim was to examine acylation stimulating protein (ASP) and its precursor complement C3, in normal, overweight, and obese Chinese children and adolescents, and the relationships with body size, blood parameters, pubertal development, family environment, and MetS. Children and adolescents (n=1603) from 6 to 18 years, boys (n=873) and girls (n=730), including normal weight (n=603), overweight (n=291) and obese (n=709) were assessed for body size parameters, pubertal development, blood lipids, glucose, insulin, ASP, and C3. ASP levels were increased in overweight and obese versus normal weight (P<0.001), while C3 showed little variation. This effect of overweight/obesity remained throughout early stages when boys and girls were separated by pubertal development or age, although age and pubertal status itself had no effect. Separation based on ASP quintiles demonstrated significant associations with blood cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-Chol), glucose, insulin, and homeostatic model assessment of insulin resistance in boys, and LDL-Chol, high-density lipoprotein cholesterol, and glucose in girls. A positive correlation with mother's body mass index in boys and girls (P=0.002 and P=0.014 respectively) as well as birth weight (P<0.001) was noted. MetS was strongly associated with increased ASP, the presence of a single MetS factor (especially hypertension, central obesity, or hyperglycemia) was associated with increased ASP. Changes in the plasma adipokine ASP in early obesity are associated with blood lipid and glucose modifications, family environment, and distinct MetS risk factors.

Truncal Distribution of Fat Mass, Metabolic Profile and Hypothalamic-Pituitary Adrenal Axis Activity in Prepubertal Obese Children

To investigate whether truncal distribution of fat mass (TDFM) is associated with variations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in prepubertal obese children. TDFM, assessed with dual energy X-ray absorptiometry and a comprehensive set of measures of HPA axis activity and reactivity have been studied in 45 prepubertal obese children aged 6 to 11 years (girls) and 6 to 13 years (boys). After adjustment for whole body fat mass (%) (WBFM), TDFM correlated positively with insulin (r = 0.50, 95% CI [0.23; 0.70]) and homeostasis model assessment of insulin resistance (r = 0.52, 95% CI [0.25; 0.71]). When adjusted for WBFM, TDFM correlated positively with morning plasma cortisol (r = 0.38, 95% CI [0.15; 0.64]) in the total population. TDFM correlated negatively with the rise of salivary cortisol after a standard meal (r = -0.43, 95% CI [-0.71; -0.02]), obviously in girls. When adjusted for WBFM and TDFM, morning plasma cortisol correlated positively with total cholesterol (r = 0.41, 95% CI [0.11; 0.65]) and triglyceride (r = 0.44, 95% CI [0.14; 0.67]). The rise of salivary cortisol after a standard meal was negatively (r = -0.56, 95% CI [-0.85; -0.01]) and positively (r = 0.74, 95% CI [0.16; 0.94]) correlated with homeostasis model assessment of insulin resistance in boys and girls, respectively. Association exists in prepubertal obese children between TDFM and markers of HPA axis activity. These data suggest that HPA axis could be involved early in life in obesity associated with pejorative metabolic profile.

Sex-related differences between adiponectin and insulin resistance in schoolchildren.

To study the effect of body composition and adiponectin on insulin resistance and beta-cell function in schoolchildren during puberty. Plasma adiponectin level and its relationships with insulin sensitivity and beta-cell function were analyzed in 500 randomly recruited nondiabetic Taiwanese schoolchildren (245 boys and 255 girls) aged 6-18 years in a national survey program for diabetes in 1999. Insulin resistance and beta-cell function were evaluated by homeostasis model assessment (HOMA). Plasma adiponectin concentrations were determined with radioimmunoassay. Plasma glucose levels remained stable, whereas insulin resistance increased with a compensatory rise in beta-cell function during this period. A transient drop of adiponectin level with a trough at 10-12 years was found in boys but not in girls. This pubertal drop of adiponectin levels in boys coincides with the sharp rise in testosterone concentration. A negative correlation between testosterone levels and adiponectin concentration was also noted in boys (r = -0.142, P = 0.032). Plasma adiponectin levels correlated inversely with relative body weight, fasting insulin concentrations, and insulin resistance index by HOMA in boys aged 15-18 years and in girls aged 11-14 years. No association was observed between adiponectin levels and beta-cell function by HOMA. There is a transient drop in the level of adiponectin during male puberty, correlated with the increase in testosterone level in boys. Plasma adiponectin levels were inversely correlated with obesity and insulin resistance in boys and girls during the pubertal period.

Association between the insulin resistance of puberty and the insulin-like growth factor-I/growth hormone axis.

To test the hypothesis that the relative insulin resistance of puberty is associated with changes in IGF-I levels, we compared IGF-I, IGF binding protein-3 (IGFBP-3), and IGFBP-1 levels to insulin resistance [M(lbm), milligrams glucose used per kilogram of lean body mass (LBM) per minute] measured during euglycemic, hyperinsulinemic clamp studies in 342 children and adolescents. IGF-I levels rose and fell during the Tanner stages of puberty in a pattern that closely followed the rise and fall of insulin resistance. IGF-I levels were significantly related to M(lbm) in boys (P = 0.0006) and girls (P = 0.02). IGF-I was significantly related to fasting insulin levels only in girls (P = 0.006; boys, P = 0.26), and this relation was significantly influenced in girls by body fat (P = 0.007), with the strongest association between IGF-I and fasting insulin seen in thin girls. IGFBP-1 correlated negatively with insulin resistance in both boys (P = 0.0004) and girls (P = 0.04), whereas IGFBP-3 correlated positively with insulin resistance in boys (P = 0.0004) but not girls (P = 0.85). These data suggest that the GH/IGF-I axis is an important contributor to the insulin resistance of puberty.