Association between Plasmatic Ceramides Profile and AST/ALT Ratio: C14:0 Ceramide as Predictor of Hepatic Steatosis in Adolescents Independently of Obesity.

OBJECTIVE: To assess the association between plasma ceramides and hepatic steatosis (HS) in adolescents, independently of obesity. MATERIALS AND METHODS: Ninety-four adolescents from two previous studies conducted and published by our crew were included. Study subjects were stratified in three groups: normal weight (n = 18), obesity (n = 34), and obesity + HS (n = 42). The presence of HS was defined when ALT/AST ratio was <1. Ceramides subspecies (C14:0, C16:0, C18:0, C24:0, and C24:1) were determined by LC/MS. RESULTS: All ceramides correlated directly with ALT levels and inversely with ALT/AST ratio; the strongest correlation was observed among C14:0 ceramide (r = 0.41 and r = -0.54, resp.; P < 0.001). Furthermore, significant correlations were observed between cholesterol and all ceramides except for C24:1 ceramide. Interestingly ceramides C14:0, C18:0, and C24:1 correlated directly with both fasting insulin and HOMA-IR index. For assessing HS, a cut-off point of 10.3 nmol/L for C14:0 ceramide reported a sensitivity of 92.7% and a specificity of 73.5% when normal weight and obesity groups (n = 52) were compared against obesity + HS group (n = 42). Positive and negative predictive values were 77.5% and 90.2%, respectively. CONCLUSIONS: Plasma ceramides are closely associated with hepatic steatosis in adolescents. C14:0 ceramide could be a novel biomarker of HS independently of obesity.

The 13C-Glucose Breath Test for Insulin Resistance Assessment in Adolescents: Comparison with Fasting and Post-Glucose Stimulus Surrogate Markers of Insulin Resistance.

OBJECTIVE: To evaluate the use of the 13C-glucose breath test (13C-GBT) for insulin resistance (IR) detection in adolescents through comparison with fasting and post-glucose stimulus surrogates. METHODS: One hundred thirty-three adolescents aged between 10 and 16 years received an oral glucose load of 1.75 g per kg of body weight dissolved in 150 mL of water followed by an oral dose of 1.5 mg/kg of U-13C-Glucose, without a specific maximum dose. Blood samples were drawn at baseline and 120 minutes, while breath samples were obtained at baseline and at 30, 60, 90, 120, 150, and 180 minutes. The 13C-GBT was compared to homeostasis model assessment (HOMA) IR (≥p95 adjusted by gender and age), fasting plasma insulin (≥p90 adjusted by gender and Tanner stage), results of 2-h oral glucose tolerance test (OGTT), insulin levels (≥65 µU/mL) in order to determine the optimal cut-off point for IR diagnosis. RESULTS: 13C-GBT data, expressed as adjusted cumulative percentage of oxidized dose (A% OD), correlated inversely with fasting and post-load IR surrogates. Sexual development alters A% OD results, therefore individuals were stratified into pubescent and post-pubescent. The optimal cut-off point for the 13C-GBT in pubescent individuals was 16.3% (sensitivity=82.8% & specificity=60.6%) and 13.0% in post-pubescents (sensitivity=87.5% & specificity=63.6%), when compared to fasting plasma insulin. Similar results were observed against HOMA and 2-h OGTT insulin. CONCLUSION: The 13C-GBT is a practical and non-invasive method to screen for IR in adolescents with reasonable sensitivity and specificity.