Impact of overweight and obesity on epicardial adipose tissue in children with type 1 diabetes.

OBJECTIVES: Epicardial adipose tissue (EAT) thickness, a novel marker of cardiovascular disease (CVD), is increased in children with a healthy weight and type 1 diabetes (T1D). The prevalence of obesity has increased in children with T1D and may confer additional CVD risk. The purpose of this study was to examine EAT thickness in youth with and without T1D in the setting of overweight/obesity. METHODS: Youth with overweight/obesity and T1D (n=38) or without T1D (n=34) between the ages of 6-18 years were included in this study. Echocardiogram using spectral and color flow Doppler was used to measure EAT and cardiac function. Waist circumference, blood pressure, and HbA1c, were used to calculate estimated glucose disposal rate (eGDR) to estimate insulin resistance in children with T1D. RESULTS: EAT thickness was not significantly different in youth with T1D compared to controls (2.10 ± 0.67 mm vs. 1.90 ± 0.59 mm, p=0.19). When groups were combined, EAT significantly correlated with age (r=0.449, p≤0.001), BMI (r=0.538, p≤0.001), waist circumference (r=0.552, p≤0.001), systolic BP (r=0.247, p=0.036), myocardial performance index (r=-0.287, p=0.015), ejection fraction (r=-0.442, p≤0.001), and cardiac output index (r=-0.306, p=0.009). In the group with T1D, diastolic BP (r=0.39, p=0.02) and eGDR (r=-0.48, p=0.002) correlated with EAT. CONCLUSIONS: EAT was associated with measures of adiposity and insulin resistance but does not differ by diabetes status among youth with overweight/obesity. These findings suggest that adiposity rather than glycemia is the main driver of EAT thickness among youth with T1D.

Intact plasma quantification of the large therapeutic lipopeptide bulevirtide.

Bulevirtide is a first-in-class entry inhibitor of the hepatitis B and hepatitis delta virus blocking the sodium/bile acid co-transporter NTCP, and was recently approved for the treatment of hepatitis D as a priority medicine (prime) in an accelerated assessment by the European Medicines Agency. It is a very large lipopeptide comprising 47 amino acids in its sequence and a myristoylation at the N-terminus. For support of clinical development, we established highly sensitive plasma quantification assays using 100 µL of plasma, spanning concentrations of 0.1 to 100 ng/mL and 1 to 1000 ng/mL with the option to measure ten-fold diluted samples up to 10,000 ng/mL. Quantification was performed with UPLC-MS/MS measurements after extraction with protein precipitation. Both assays were fully validated according to the pertinent guidelines of the FDA and EMA, including incurred sample reanalyses and cross-validation using clinical study samples. Graphical abstract.