Browsing by Author "Santoro, Nicola"

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    Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes
    (Oxford University Press, 2021) Galderisi, Alfonso; Moran, Antoinette; Evans-Molina, Carmella; Martino, Mariangela; Santoro, Nicola; Caprio, Sonia; Cobelli, Claudio; Pediatrics, School of Medicine
    Context: Clinical onset of type 1 diabetes (Stage 3 T1D) is preceded by a presymptomatic phase characterized by multiple islet autoantibodies with normal glucose tolerance (Stage 1 T1D). Objective: The aim was to explore the metabolic phenotypes of β-cell function and insulin sensitivity and clearance in normoglycemic youth with Stage 1 T1D and compare them with healthy nonrelated peers during a 3-hour oral glucose tolerance test (OGTT). Methods: Twenty-eight lean youth, 14 with ≥2 islet autoantibodies (cases) and 14 healthy controls underwent a 3-hour 9-point OGTT with measurement of glucose, C-peptide, and insulin. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI=φtotal×SI). Fasting insulin clearance (CL0) was calculated as the ratio between the fasting insulin secretion rate (ISR) and plasma insulin levels (ISR0/I0), while postload clearance (CL180) was estimated by the ratio of AUC of ISR over the plasma insulin AUC for the 3-hour OGTT (ISRAUC/IAUC). Participants with impaired fasting glucose, impaired glucose tolerance, or any OGTT glucose concentration ≥200 mg/dL were excluded. Results: Cases (10.5 years [8, 15]) exhibited reduced DI (P < .001) due to a simultaneous reduction in both φtotal (P < 0.001) and SI (P = .008) compared with controls (11.5 years [10.4, 14.9]). CL0 and CL180 were lower in cases than in controls (P = .005 and P = .019). Conclusion: Presymptomatic Stage 1 T1D in youth is associated with reduced insulin sensitivity and lower β-cell responsiveness, and the presence of blunted insulin clearance.
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    Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?
    (Mary Ann Liebert, 2018-11-30) Tricò, Domenico; Di Sessa, Anna; Caprio, Sonia; Chalasani, Naga; Liu, Wanqing; Liang, Tiebing; Graf, Joerg; Herzog, Raimund I.; Johnson, Casey D.; Umano, Giuseppina Rosaria; Feldstein, Ariel E.; Santoro, Nicola; Medicine, School of Medicine
    We tested whether oxidized linoleic acid metabolites (OXLAM) are associated with pediatric metabolic syndrome (MetS) and a proatherogenic lipoprotein profile in 122 obese adolescents. Furthermore, we examined whether genetic and metagenomic factors can modulate plasma OXLAM concentrations by genotyping the fatty acid desaturase 1/2 (FADS) gene and by characterizing the gut microbiota. Subjects with MetS (n = 50) showed higher concentrations of 9- and 13-oxo-octadecadienoic acid (9- and 13-oxo-ODE) than subjects without MetS (n = 72). Both metabolites were associated with an adverse lipoprotein profile that was characterized by elevated very small-dense low-density lipoprotein (p < 0.005) and large very low-density lipoprotein particles (p = 0.01). Plasma 9- and 13-oxo-ODE were higher in subjects carrying the haplotype AA of the FADS gene cluster (p = 0.030 and p = 0.048, respectively). Furthermore, the reduced gut bacterial load was associated with higher 9-oxo-ODE concentrations (p = 0.035). This is the first study showing that high plasma OXLAM concentrations are associated with MetS and suggesting that the leading factors for high plasma concentrations of OXLAM might be the genetic background and the composition of the gut microbiota. In conclusion, high concentrations of 9- and 13-oxo-ODE, which may be the result of a genetic predisposition and a reduced gut bacterial load, are associated with MetS and with a proatherogenic lipoprotein profile in obese adolescents.