Changes in liver enzymes are associated with changes in insulin resistance, inflammatory biomarkers and leptin in prepubertal children with obesity.

BACKGROUND: Non-alcoholic fatty liver disease is associated with obesity. A subclinical inflammation state, endothelial dysfunction, and parameters related to metabolic syndrome (MetS), have been documented in children with obesity. We aimed to determine the changes that occur in liver enzymes levels in response to the standard treatment of childhood obesity, also assessing any associations with liver enzyme levels, leptin, and markers of insulin resistance (IR), inflammation, and parameters related to MetS in prepubertal children. METHODS: We carried out a longitudinal study in prepubertal children (aged 6-9 years) of both sexes with obesity; a total of 63 participants were recruited. Liver enzymes, C-reactive protein (CRP), interleukin-6, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), soluble intercellular adhesion molecule-1 (sICAM-1), leptin, homeostasis model assessment for IR (HOMA-IR), and parameters related to MetS were measured. RESULTS: After standard treatment for 9 months, children who lowered their standardised body mass index (SDS-BMI) had significantly lower systolic blood pressure (p = 0.0242), diastolic blood pressure (p = 0.0002), HOMA-IR (p = 0.0061), and levels of alanine aminotransferase (ALT) (p = 0.0048), CRP (p = 0.0001), sICAM-1 (p = 0.0460), and IL-6 (p = 0.0438). There was a significant association between the changes that occur with treatment, in the ALT levels, and changes in leptin (p = 0.0096), inflammation biomarkers [CRP (p = 0.0061), IL-6 (p = 0.0337), NLR (p = 0.0458), PLR (p = 0.0134)], and HOMA-IR (p = 0.0322). CONCLUSION: Our results showed that a decrease in ALT levels after the standard treatment for 9 months was associated with favourable changes in IR markers (HOMA-IR) and inflammation (IL-6, CRP, NLR, and PLR).

Liver Enzymes Correlate With Metabolic Syndrome, Inflammation, and Endothelial Dysfunction in Prepubertal Children With Obesity.

Background: Metabolic syndrome (MetS) can start in children with obesity at very young ages. Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic component of metabolic syndrome. If left untreated, the clinical course of NAFLD can be progressive and can become chronic if not detected at an early stage. Objective: We aimed to quantify the differences in liver enzymes between prepubertal children with obesity and children with normal weight to determine any associations between them and parameters related to MetS, adipokines, or markers of endothelial dysfunction and inflammation. Methods: This cross-sectional study included 54 prepuberal children with obesity (aged 6-9 years) and 54 children with normal weight, matched by age and sex. Liver enzymes, C-reactive protein (CRP), interleukin-6, soluble intercellular adhesion molecule-1 (sICAM-1), adipokines, and parameters related to metabolic syndrome (MetS) were all measured. Results: Alanine aminotransferase (ALT) levels, serum butyryl cholinesterase (BChE), leptin, CRP, sICAM-1, triglycerides, blood pressure, and homeostasis model assessment for insulin resistance were significantly higher in children with obesity, while Apolipoprotein A-1, HDL-cholesterol, and adiponectin were significantly lower. In the children with obesity group, ALT and BChE levels correlated with anthropometric measurements, insulin resistance, and lipid parameters, leptin, interleukin-6, CRP, and sICAM-1 while BChE levels negatively correlated with adiponectin. Conclusions: Compared to children with normal weight, prepubertal children with obesity had elevated values for liver enzymes, leptin, markers of insulin resistance, inflammation, and endothelial dysfunction, and variables associated with MetS. There was also a correlation between these disorders and liver enzyme levels.

Effects of growth hormone therapy on metabolic parameters, adipokine and endothelial dysfunction in prepuberal children.

AIM: To determine whether non-obese prepubertal children with growth hormone deficiency (GHD) present changes in lipid metabolism, and adipokines, and to assess the short-term effects of growth hormone (GH) treatment on these parameters. METHODS: Prospective observational follow-up and case-control (36 GHD children and 38 healthy children) study lasted for six months. Means of values from groups were compared, control group versus GHD baseline group, and GHD baseline group versus GHD after six months of GH replacement therapy. Lipid profile, glucose, insulin, homeostatic model assessment - insulin resistance (HOMA-IR), leptin, adiponectin and soluble intercellular adhesion molecule-1 (sICAM-1) were all analysed. RESULTS: Growth hormone deficiency children show higher baseline levels of total cholesterol, LDL cholesterol, triglycerides, Apo B and sICAM-1, but lower levels of free fatty acids, insulin and HOMA-IR. After six months of treatment, cholesterol, LDL cholesterol, Apo B, T cholesterol/HDL cholesterol, insulin, HOMA-IR and leptin levels decreased. The changes in insulin and HOMA-IR levels correlated inversely with the changes in HDL cholesterol and Apo A1 levels. A correlation was also observed between the changes in adiponectin levels and the changes in HDL cholesterol and Apo A1 levels. Variations in leptin levels were correlated with changes in triglycerides. CONCLUSION: Prepubertal non-obese GHD children present altered lipid profiles and adipokine levels. Replacement therapy with GH improves these variables.

Association of serum uric acid levels to inflammation biomarkers and endothelial dysfunction in obese prepubertal children.

BACKGROUND: High serum uric acid (SUA) levels are present in patients with metabolic syndrome (MetS), when the latter is associated with endothelial dysfunction, inflammation, and hypertension. This increase in SUA levels may have a key role in cardiovascular diseases. OBJECTIVE: We aim to quantify the differences in inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS in obese prepubertal children compared to non-obese children, and determine if there is a relationship between uric acid levels and these variables. METHODS: A cross-sectional study was carried out on obese children (6-9 yr old). The study included 43 obese children and the same number of non-obese children (control group), matched by age and sex. SUA, C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), glucose, insulin, lipid profile, and blood pressure were all measured. RESULTS: SUA levels, CRP, and sICAM-1 were significantly higher in obese children. In the obese group, SUA levels showed a positive correlation with body mass index (BMI), insulin, homeostasis model assessment for insulin resistance (HOMA-IR), CRP, IL-6, sICAM-1, and triglycerides (TGs), and correlated negatively with high-density lipoprotein cholesterol (HDL-C) and Apo-AI, but not with Apo-B. When adjusted for age, sex, and creatinine, it was noted that SUA levels are independent predictive factors for sICAM-1, CRP, and IL-6. CONCLUSIONS: Inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS are elevated in obese prepubertal children and correlate to uric acid levels.

Relationship between changes in plasma leptin concentrations and plasminogen activator inhibitor-1 in obese prepubertal children after nine months of treatment.

BACKGROUND/AIMS: The metabolic syndrome (MS) is associated with insulin resistance (IR), inappropriate fibrinolysis and high plasma leptin concentrations. The aim of this study was to quantify fibrinolysis and MS-related variables in obese prepubertal children and to evaluate changes in these variables as a result of improved body mass index (BMI), IR and leptin levels following 9 months of treatment. METHODS: The homeostasis model assessment for insulin resistance (HOMA-IR), leptin, plasminogen activator inhibitor-1 (PAI-1) and lipid profile were studied at baseline in obese (n = 50) and nonobese children (n = 50), and after 9 months of treatment in obese children. RESULTS: In the cross-sectional study the mean values for insulin, HOMA-IR, triglycerides, leptin and PAI-1 were significantly higher in obese children than in controls. High-density lipoprotein cholesterol (HDLc) and apolipoprotein A-1 were significantly lower. In the longitudinal study, after 9 months, children with lowered BMI standard deviation score displayed a significant decrease in insulin, HOMA-IR, PAI-1, leptin and triglyceride levels, and an increase in HDLc. Only leptin proved to be an independent predictive factor for changes in PAI-1 (p = 0.010). CONCLUSION: Obesity-linked disorders appear in obese children prior to puberty; these disorders can be improved by decreasing BMI. Changes in leptin levels were found to independently predict changes in PAI-1 in obese children and can help to diagnose complications associated with the obesity.

Short-term effects of GH treatment on coagulation, fibrinolysis, inflammation biomarkers, and insulin resistance status in prepubertal children with GH deficiency.

OBJECTIVE: The aims of this study was to determine whether prepubertal GH deficiency (GHD) children showed any impairment in coagulation- and fibrinolysis-related parameters and in inflammatory and insulin resistance markers and to evaluate the effect of short-term GH therapy on these parameters. DESIGN: This was a 6-month, prospective, observational, case-control study (36 prepubertal children with GHD and 38 healthy prepubertal children with no differences in BMI). Comparison of study parameter values in GHD AND control groups at baseline and after 6 months of GH treatment in the GHD group. The following were analyzed: glucose, insulin, fibrinogen, absolute plasminogen activator inhibitor type 1 (aPAI-1), von Willebrand factor (vWF), homeostasis model assessment for insulin resistance (HOMA-IR) index, C-reactive protein (CRP), and interleukin 6 (IL6) levels. RESULTS: Children with GHD showed higher baseline levels of aPAI-1 and fibrinogen and lower levels of glucose, insulin, and HOMA-IR index than healthy controls. No intergroup differences were found for vWF. After 6 months of treatment, aPAI-1 levels were lower but no changes were observed in fibrinogen or vWF levels, which were similar to those of controls. Glucose levels increased, though not significantly, while insulin levels and HOMA-IR index rose to normal levels. A positive correlation was found between changes in insulin status/HOMA-IR index and levels of aPAI-1, fibrinogen, vWF, CRP, and IL6. CONCLUSIONS: At early ages, GH therapy appears to exert beneficial effects on the amount of aPAI-1. At the same time, it increases the state of insulin resistance (HOMA-IR index) without modifying the levels of fibrinogen, vWF, CRP, and IL6.

Changes in body mass index are associated with changes in inflammatory and endothelial dysfunction biomarkers in obese prepubertal children after 9 months of body mass index SD score loss.

The metabolic syndrome is associated with insulin resistance, a systemic low-grade inflammatory state, and endothelial dysfunction. These disorders may arise at a very early age in obese children. The aim of this study was to confirm changes in endothelial dysfunction and inflammatory biomarkers in obese prepubertal children and to evaluate the effect of body mass index (BMI) modification on these biomarkers. Biomarkers for inflammation, endothelial dysfunction, and insulin resistance were measured in obese children (47) and healthy controls (47). Baseline pretreatment levels of insulin (P = .019), homeostasis model assessment of insulin resistance (P = .004), soluble intercellular adhesion molecule (sICAM) (P = .003), and C-reactive protein (CRP) (P < .001) were significantly higher in obese children than in controls. After 9 months of treatment, obese children with lowered BMI SD score (SDS-BMI) displayed a significant decrease in insulin (P = .011), homeostasis model assessment of insulin resistance (P = .012), CRP (P = .006), and interleukin-6 (IL-6) (P = .045) levels compared with obese children with stable SDS-BMI; they also displayed a nonsignificant drop in sICAM levels. Similarly, obese children with lowered SDS-BMI displayed a decrease in CRP (P = .005) and IL-6 (P = .065) compared with baseline levels before treatment. In the total obese group, changes in SDS-BMI correlated positively with changes in CRP (P = .035), IL-6 (P = .027), and sICAM-1 (P = .038) levels. Only SDS-BMI was an independent predictive factor for CRP (P = .031), IL-6 (P = .027), and sICAM-1 (P = .033). Prepubertal obese children displayed alterations indicative of endothelial dysfunction, insulin resistance, and inflammatory state. Lowering of the SDS-BMI after 9 months of treatment was associated with an improvement in these variables compared with those in obese children with stable SDS-BMI status.

Hyperhomocysteinemia correlates with insulin resistance and low-grade systemic inflammation in obese prepubertal children.

Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin (P = .003), C-reactive protein (P = .033), and leptin (P < .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group (P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .001) and leptin (P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .005) and leptin (P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity.

Metabolic cardiovascular syndrome in obese prepubertal children: the role of high fasting insulin levels.

The aim of this study was to detect the presence and degree of impairment of cardiovascular disease (CVD) risk factors, grouped as metabolic cardiovascular syndrome (MCS), in obese prepubertal children. We also assessed the influence of high fasting insulin levels in this pathological status. A cross-sectional study was performed on obese children based on fasting blood samples. Subjects were 61 obese children (aged 6 to 9 years) and an equal number of non-obese children paired by age and sex. The obese children presented the following characteristics in comparison to the non-obese group: significantly high levels of insulin (8.2 +/- 0.52 v 6.12 +/- 0.34 microU/mL), triglycerides (TG) (0.79 +/- 0.04 v 0.60 +/- 0.02 mmol/L), uric acid (0.24 +/- 0.005 v 0.21 +/- 0.004 mmol/L), systolic (SBP) (94.59 +/- 1.06 v 88.85 +/- 1.2 mm Hg) and diastolic (56.49 +/- 1.07 v 52.21 +/- 1.06 mm Hg) blood pressure (DBP), and low levels of high-density lipoprotein cholesterol (HDL-C) (1.30 +/- 0.04 v 1.46 +/- 0.03 mmol/L), and nonesterified fatty acids (0.407 +/- 0.02 v 0.505 +/- 0.02 mmol/L). The hyperinsulinemic obese children showed the same types of differences when compared with the normoinsulinemic group. In the obese group, having adjusted for age, waist/hip ratio (WHR), body mass index (BMI), and sex hormone-binding globulin (SHBG), insulin was an independent prediction factor for triglycerides (P =.0004), apolipoprotein A-I (Apo-AI) (P =.005), and alanine aminotransferase (ALT) (P =.029). BMI was an independent prediction factor for HDL-C (P =.001) and triglycerides (P =.027). However, insulin was an independent prediction factor in the control group for triglycerides (P =.0002) and SBP (P =.012), just as BMI was for HDL-C (P =.011) and uric acid (P =.041). We conclude that the cluster of CVD risk factors associated with MCS and intra-abdominal fat is present in obese prepubertal children. This situation seems to depend, to a large extent, on the insulin basal level. The apparent association between BMI and MCS is due to the correlation between BMI and insulin, and to the fact that insulin associates with MCS. Within the obese group, hyperinsulinemic children present the greatest impairment in the parameters considered to be constituents of MCS.