Periodic 48 h feed withdrawal improves glucose tolerance in growing pigs by enhancing adipogenesis and lipogenesis

Background

Adipocyte numbers and peroxisome proliferators activated receptor?? (PPAR??) expression of retroperitoneal tissue increased while area under the curve (AUC) during the glucose tolerance test (GTT) was reduced in rats subjected to certain feed withdrawal (FW) regimens. Thus, using pigs as the experimental model, the hypothesis that FW regimens influence glucose tolerance by influencing fat cell function was evaluated with the objective of determining the effect of a single (FWx1; at age of 19 wk for 48 h) or periodic, multiple (FWx4; 24 h FW at 7 and 11 wk of age and 48 h FW at 15 and 19 wk of age) FW on AUC of glucose and insulin during the GTT relative to pigs that did not experience FW (Control).

Methods

Growth, body composition, adipocyte numbers, PPAR?? expression, lipogenic potential as glucose uptake into fat of adipocytes of varying diameter in omental (OM) and subcutaneous (SQ) fat as affected by FW regimens were determined in pigs initiated into the study at 5 wk of age and fed the same diet, ad libitum.

Results

Blood glucose concentrations for prior to and 120 min post glucose meal tended to be lower (p = 0.105 and 0.097, respectively) in pigs in FW treatments. In OM fat; cell numbers, glucose Universal¹⁴C [U¹⁴C] incorporation into fat and rate of incorporation per 10⁴ cells was greatest for cells with diameters of 90-119 ??m. Pigs undergoing FWx4 tended to have greater (p = 0.0685; by 191%) number of adipocytes, increased (p = 0.0234) glucose U¹⁴C incorporation into adipocytes and greater (p = 0.0872) rate of glucose uptake into cells of 119-150 ??m diameter than of cells from control or FWx1 pigs. Subcutaneous adipocyte numbers in 22-60 and 61-90 ??m diameter ranges from pigs in FWx1 tended to be greater (p = 0.08 and 0.06, respectively) than for those in FWx4 treatment, yet PPAR?? expression and total cell number were not affected by treatment.

Conclusions

Results suggest that FW regimens influence fat cell function or lipogenesis rather than number, affecting glucose metabolism and may have implications in drug-free control of metabolic syndrome symptoms.     

Performance of a novel human immunodeficiency virus (HIV) type 1 total nucleic acid-based real-time PCR assay using whole blood and dried blood spots for diagnosis of HIV in infants

The new Cobas AmpliPrep/Cobas TaqMan HIV-1 Qual test offers advanced automation for the detection of human immunodeficiency virus type 1 (HIV-1) RNA and DNA in dried blood spots (DBS) and whole blood. An analytical evaluation using an HIV-1 secondary standard yielded limits of detection of 514, 710, and 1,090 HIV RNA copies/ml for EDTA plasma, whole blood, and DBS, respectively. The precision and reproducibility of HIV-1 detection was equivalent for DBS and whole blood. Inclusivity was demonstrated for a reference panel of HIV-1 subtypes A to N. A clinical evaluation of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Qual test was performed at a center for routine diagnostics in Johannesburg, South Africa, using 1,013 clinical specimens from HIV-1 exposed children. The Amplicor HIV-1 DNA test v1.5 with the MagNApure DNA isolation procedure was used as the reference method. A total of 995 valid results for whole blood with both methods yielded 691 and 303 concordant negative and positive results for the Cobas AmpliPrep/Cobas TaqMan HIV-1 Qual test, respectively. For the 800 valid DBS specimen results, 495 and 300 concordant negative and positive results were obtained, respectively. The resulting clinical specificities and sensitivities of the new test were 100% and 99.7% for whole blood and DBS, respectively. The new test was characterized by its robustness, enhanced automation, and improved sample throughput. The Cobas AmpliPrep/Cobas TaqMan HIV-1 Qual test will support early, reliable diagnosis of HIV in children in routine laboratory settings.     

The cost-effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: A European health-economic analysis of the DELIVER trial

Aims

To determine the cost-effectiveness of dapagliflozin, added to usual care, in patients with heart failure (HF) with mildly reduced or preserved ejection fraction for the UK, German and Spanish payers using detailed patient-level data from the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial.

Methods and results

A lifetime Markov state-transition cohort model was developed. Quartiles of the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) defined health states and monthly transition count data informed transition probabilities. Multivariable generalized estimating equations captured the incidence of HF hospitalizations and urgent HF visits, while cardiovascular deaths and all-cause mortality were estimated using adjusted parametric survival models. Health state costs were assigned to KCCQ-TSS quartiles (2021 British pound [GBP]/Euro) and patient-reported outcomes were sourced from DELIVER. Future values of costs and effects were discounted according to country-specific rates. In the UK, dapagliflozin treatment was predicted to increase quality-adjusted life years (QALYs) and life-years by 0.231 and 0.354, respectively, and extend the time spent in the best quartile of KCCQ-TSS by 4.2 months. Comparable outcomes were projected for Germany and Spain. The incremental cost-effectiveness ratios were £7761, €9540 and €5343/QALY in the UK, Germany and Spain, respectively. According to regional willingness-to-pay thresholds, 91%, 89% and 92% of simulations in the UK, Germany and Spain, respectively, were cost-effective following probabilistic sensitivity analyses.

Conclusion

Dapagliflozin, added to usual care, is very likely cost-effective for HF with mildly reduced or preserved ejection fraction in several European countries.