Association between Fasting and Postprandial Levels of Liver Enzymes with Metabolic Syndrome and Suspected Prediabetes in Prepubertal Children.

Elevated liver enzyme activity may be associated with metabolic syndrome (MetS); however, it is not included in the MetS definition for children. Postprandial changes in the levels of biochemistry tests are related to manifestations of metabolic abnormalities. We assessed the association between fasting and postprandial liver enzymes levels with MetS and elevated hemoglobin A1c (HbA1c) in children aged 9-11. The study included 51 girls and 48 boys, all presumably healthy. In all participants' anthropometric indices, fasting glucose, insulin, lipid profile and HbA1c were measured. Enzymes, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were assayed in fasting and postprandial states. Individuals were divided into subgroups: with (MetS(+): n = 26); without MetS (MetS(-): n = 73); with HbA1c levels ≤ 5.3% (n = 39); and ≥5.7% (n = 11). Elevated fasting GGT levels were found in 23% of MetS(+) children and rarely in MetS(-) children; increased postprandial GGT was noted in 35% of MetS(+) individuals. Postprandial GGT changes tend to predict MetS (OR = 1.16; p = 0.092). Increased fasting ALT was found rarely in MetS(+) children, but did not occur in MetS(-) children. HbA1c ≥ 5.7% occurred rarely and neither fasting ALT nor GGT were related to elevated HbA1c. However, postprandial change of ALT was a good positive predictor of increased HbA1c (OR = 1.33; p = 0.021). Postprandial GGT performs better as an indicator of metabolic syndrome occurrence, and instead postprandial ALT may predict prediabetes in prepubertal children.

Validation of Becton Dickinson Barricor™ tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I measuring systems.

BACKGROUND: BD Barricor™ tubes have been proposed to decrease laboratory turnaround time (TAT). We analytically validated and then clinically verified these tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I (hs-cTnI) assays. METHODS: hs-cTnI measurements were undertaken in paired Barricor™ and in-use PSTII™ tubes on both systems. 359 matched samples with hs-cTnI levels between 3 and 15,000 ng/L (Atellica® values) were used to assess the hemolysis rate and make method comparisons. 599 paired patient samples were collected on emergency department (ED) admission to compare the performance of the rapid acute myocardial infarction (AMI) rule-out strategy based on hs-cTnI concentrations lower than recommended thresholds (<4 ng/L Alinity™; <5 ng/L Atellica®) when different tubes and systems were employed. RESULTS: No between-tube differences in hemolysis rate were seen when free hemoglobin concentrations in plasma samples were ≥0.25 g/L, even if PSTII™ showed a significant increase of hemolysis rate vs. Barricor™ (31% vs. 22%, p=0.007) when a lower cut-off for hemolysis (≥0.11 g/L) was employed on the Atellica® detection system. The alternate use of these tubes did not influence the hs-cTnI results obtained from either of the two assays, which remained markedly biased (~40%) irrespective of the tube used. The expected optimal ability of very low hs-cTnI values on ED admission for ruling out AMI was confirmed by using both systems regardless of the tube type. CONCLUSIONS: Barricor™ and PSTII™ tubes can provide analytically equivalent hs-cTnI results when used on either Alinity™ or Atellica® hs-cTnI assays.

Diagnostic Performance of Biomarker-Based Scores as Predictors of Metabolic Dysfunction-Associated Fatty Liver Disease Risk in Healthy Children.

INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD)-a new definition for non-alcoholic fatty liver disease-reflects the impact of metabolic abnormalities on liver function. We assessed the diagnostic accuracy of biomarker-based scores for prediction of MAFLD in apparently healthy children. METHODS: This study included 144 children aged 9-11. MAFLD was recognized in 14 girls and 29 boys. Anthropometric indices, glycemia, insulin resistance, lipid profile, enzymes (ALT, AST, GGT, ALP), CRP, N-terminal propeptide of type I procollagen (P1NP) and collagen type I C-telopeptide (CTX-1) levels were measured. Fatty liver and hepatic steatosis index (FLI, HSI) and potential indicators of liver fibrogenesis: P1NP/ALP, P1NP/ALPxALT, P1NP/ALPxCRP were calculated. RESULTS: P1NP/ALPxALT and P1NP/ALPxCRP were significantly higher in subjects with MAFLD. FLI was a good, significant predictor of MAFLD occurrence, regardless of sex. In boys, P1NP/ALPxCRP was a comparable predictor as CRP (OR 1.14 vs. 1.17; p < 0.001). P1NP/ALPxCRP had better discrimination capability in boys (AUC = 0.79; p < 0.001). However, the use of this algorithm did not improve discriminatory power in comparison to CRP (AUC = 0.81; p < 0.001), but gave a better sensitivity for MAFLD prediction (86% vs. 59%). CONCLUSIONS: We suggest that P1NP/ALPXCRP is a reliable tool for MAFLD prediction in routine pediatric practice.

Relationships between Bone Turnover Markers and Factors Associated with Metabolic Syndrome in Prepubertal Girls and Boys.

The associations between individual components of metabolic syndrome (MetS) and bone health in children are complex, and data on this topic are sparse and inconsistent. We assessed the relationship between bone turnover markers and markers of the processes underlying MetS (insulin resistance and inflammation) in a group of presumably healthy children aged 9-11 years: 89 (51 girls, 38 boys) presenting without any features of MetS and 26 (10 girls, 16 boys) with central obesity and two features of MetS. Concentrations of glucose, triglycerides (TG), HDL cholesterol (HDL-C), C-reactive protein (CRP), HbA1c, total 25-hydroxyvitamin D (25(OH)D), intact-P1NP (N-terminal propeptide of type I procollagen), CTX-1 (C-terminal telopeptide of type I collagen) were assayed and insulin resistance was assessed (HOMA-IR). BMI centile, waist circumference (WC) and blood pressure were measured. The presence of MetS in girls resulted in significantly lower concentrations of CTX-1 and a trend to lower CTX-1 in boys. The concentrations of bone formation marker i-P1NP were not affected. Among the features associated with MetS, HOMA-IR appeared as the best positive predictor of MetS in girls, whereas CRP was the best positive predictor in boys. A significant influence of HOMA-IR on the decrease in CTX-1 in girls was independent of BMI centile and WC, and the OR of having CTX-1 below the median was 2.8-fold higher/1SD increased in HOMA-IR (p = 0.003). A weak relationship between CTX-1 and CRP was demonstrated in girls (r = -0.233; p = 0.070). Although TG, as a MetS component, was the best significant predictor of MetS in both sexes, there were no correlations between bone markers and TG. We suggest that dyslipidemia is not associated with the levels of bone markers in prepubertal children whereas CRP is weakly related to bone resorption in girls. In prepubertal girls, insulin resistance exerts a dominant negative impact on bone resorption, independent of BMI centile and waist circumference.

Low Serum 25-hydroxyvitamin D Level Does Not Adversely Affect Bone Turnover in Prepubertal Children.

Both vitamin D and insulin-like growth factor 1 (IGF-1) play essential roles in bone metabolism and may interact during prepubertal bone accrual. We investigated the association of low serum 25-hydroxyvitamin D (25(OH)D) (<20 ng/mL) with the circulating bone turnover markers, when compared to their interaction with IGF-1. SUBJECTS AND METHODS: Serum 25(OH)D, IGF-I, P1NP (N-terminal propeptide of type I procollagen), and CTX-1 (C-terminal telopeptide of type I collagen) were measured, and the bone turnover index (BTI) was calculated in 128 healthy children, aged 9-11 years. RESULTS: Mean 25(OH)D concentration was 21.9 ± 4.9 ng/mL, but in 30.5% of participants it was <20 ng/mL (<50 nmol/L). We observed a trend for higher P1NP (p < 0.05) and IGF-1 (p = 0.08), towards lower 25(OH)D in tertiles. Levels of P1NP in the lowest 25(OH)D tertile (<20 ng/mL) were the highest, while CTX and BTI remained unchanged. Additionally, 25(OH)D negatively correlated with IGF-1, while the correlation with P1NP was not significant. A strong positive correlation of IGF-1 with P1NP and BTI but weak with CTX was observed. Low 25(OH)D (<20 ng/mL) explained 15% of the IGF-1 variance and 6% of the P1NP variance. CONCLUSIONS: Low levels of 25(OH)D do not unfavorably alter bone turnover. It seems that serum 25(OH)D level may not be an adequate predictor of bone turnover in children.

Relationship between Serum Angiopoietin-like Proteins 3 and 8 and Atherogenic Lipid Biomarkers in Non-Diabetic Adults Depends on Gender and Obesity.

Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25-74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.

Effect of fasting hyperglycemia and insulin resistance on bone turnover markers in children aged 9-11 years.

AIM: Impaired regulation of glucose metabolism in childhood adversely affects bone health. We assessed the effect of fasting hyperglycemia and insulin resistance on bone turnover markers in prepubertal children with normal glycemia (<100 mg/dL) and fasting hyperglycemia (100-125 mg/dL). METHODS: Glucose, hemoglobin A1c, IGF-I (insulin-like growth factor I), iP1NP (N-terminal propeptide of type I procollagen), CTX-1 (C-terminal telopeptide of type I collagen) and insulin were measured. Bone turnover index (BTI) and HOMA-IR (homeostasis model assessment) were calculated. RESULTS: Bone resorption marker (CTX) levels were decreased by 26.5% in boys with hyperglycemia, though only 7% in girls. Hyperglycemia had no effect on the bone formation marker iP1NP. IGF-1, the best predictor of bone marker variance accounted for 25% of iP1NP and 5% of CTX variance. Girls presented significantly higher BTI indicating the predominance of bone formation over resorption. Insulin resistance significantly decreased CTX. In girls, HOMA-IR and IGF-1 predicted 15% of CTX variance. CONSLUSIONS: Fasting hyperglycemia and insulin resistance in children impact bone turnover suppressing bone resorption. Hyperglycemia decreased resorption, particularly in boys, while suppression of resorption by insulin resistance was more pronounced in girls. We suggest that the progression of disturbances accompanying prediabetes, may interfere with bone modelling and be deleterious to bone quality in later life.

Association between Fasting Glucose Concentration, Lipid Profile and 25(OH)D Status in Children Aged 9⁻11.

BACKGROUND: The aim of this study was to assess the relationship between vitamin D status and the prevalence of dyslipidemia and impaired fasting glucose (IFG) in children. Methods and Summary: 284 children (150 boys and 134 girls) aged 9⁻11 were included in the study. Children with deficient 25(OH)D (25-hydroxycholecalciferol) levels ≤20 ng/mL (50 nmol/L) were characterized by a more frequent occurrence of impaired fasting glucose (IFG) (Odd ratios (OR) = 1.966, 95% confidence interval (CI): 1.055⁻3.663; p = 0.033) when compared to children with 25(OH)D >20 ng/mL. Serum 25(OH)D with concentration lower by 1 ng/mL (2.5 nmol/L) was linked to higher fasting glucose (by 0.25 mg/dL, 0.013 mmol/L; p = 0.017), higher total cholesterol (TC) by almost 1 mg/dL (0.96 mg/dL, 0.25 mmol/L; p = 0.006) and higher high-density lipoprotein cholesterol (HDL-C) (by 0.57 mg/dL, 0.015 mmol/L; p < 0.001). CONCLUSION: 25(OH)D deficiency may negatively affect fasting glucose and total cholesterol concentration in children aged 9⁻11. Vitamin D-deficient children are twice as likely to develop prediabetes as reflected by impaired fasting glucose when compared to those with a 25(OH)D level above 20 ng/mL (50 nmol/L).

Non-fasting lipid profile determination in presumably healthy children: Impact on the assessment of lipid abnormalities.

OBJECTIVE: Despite the common use of non-fasting measurements for lipid profile in children it remains unclear as to the extent non-fasting conditions have on laboratory results of lipids measurements. We aimed to assess the impact of non-fasting lipid profile on the occurrence of dyslipidemia in children. MATERIALS AND METHODS: Basic lipid profile including: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), as well as small, dense-LDL-C (sd-LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)], were measured in 289 presumably healthy children aged 9-11 in both fasting and non-fasting condition. The clinical impact of non-fasting lipid profile was evaluated individually for each child with estimation of false positive (FP) and false negative (FN) results. RESULTS: The highest percentage of FP results in non-fasting condition was observed for TG (42.3%) being significantly higher when compared to FN results (p = 0.003). In contrast, the highest percentage of FN results in a non-fasting state were shown for LDL-C (14.3%), but the difference was statistically insignificant when compared to FP results. When comparing fasting and non-fasting lipid profile a number of significant differences was shown for: TG (p<0.001), HDL-C (p = 0.002) LDL-C (p<0.001) and ApoAI (p<0.001), respectively. The occurrence of dyslipidemia, recognized on the basis of non-fasting lipids was significantly higher (p = 0.010) when compared to fasting lipid profile. CONCLUSIONS: A higher occurrence of dyslipidemia, based on the measurement of non-fasting lipids in children, is suggestive of possible disorders in lipid metabolism. However, accurate identification of dyslipidemia by assessment of non-fasting lipids requires the establishment of appropriate cut-off values for children.