Comparative Effectiveness of DPP-4 Inhibitors Versus Sulfonylurea for the Treatment of Type 2 Diabetes in Routine Clinical Practice: A Retrospective Multicenter Real-World Study

Introduction: DPP-4 inhibitors (DPP4i) and sulfonylureas are popular second-line therapies for type 2 diabetes (T2D), but there is a paucity of real-world studies comparing their effectiveness in routine clinical practice. Methods: This was a multicenter retrospective study on diabetes outpatient clinics comparing the effectiveness of DPP4i versus gliclazide extended release. The primary endpoint was change from baseline in HbA1c. Secondary endpoints were changes in fasting plasma glucose, body weight, and systolic blood pressure. Automated software extracted data from the same clinical electronic chart system at all centers. Propensity score matching (PSM) was used to generate comparable cohorts to perform outcome analysis. Results: We included data on 2410 patients starting DPP4i and 1590 patients starting gliclazide (mainly 30–60 mg/day). At baseline, the two groups differed in disease duration, body weight, blood pressure, HbA1c, fasting glucose, HDL cholesterol, triglycerides, liver enzymes, eGFR, prevalence of microangiopathy, and use of metformin. Among DPP4i molecules, no difference in glycemic effectiveness was detected. In matched cohorts (n = 1316/group), patients starting DPP4i, as compared with patients starting gliclazide, experienced greater reductions in HbA1c (− 0.6% versus − 0.4%; p < 0.001), fasting glucose (− 14.1 mg/dl versus − 8.8 mg/dl; p = 0.007), and body weight (− 0.4 kg versus − 0.1 kg; p = 0.006) after an average 6 months follow-up. DPP4i improved glucose control more than gliclazide, especially in patients who had failed with other glucose-lowering medications or were on basal insulin. Conclusions: This large retrospective real-world study shows that, in routine clinical practice, starting a DPP4i allows better glycemic control than starting low-dose gliclazide. Funding: The Italian Diabetes Society, with external support from AstraZeneca

Critical analysis of the value of the rabbit median nerve model for biomedical research on peripheral nerve grafts.

The rabbit has been proposed to represent an animal model that allows studying peripheral nerve regeneration across extended gap lengths. We describe here our experiences with the rabbit median nerve model and the obstacles it comes along with. This short communication is meant to inform the community and to prevent other researcher from investing time and animal lives in a model with low translational power

Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes

Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by Eco™ Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 x 10-4) and GC rs4588 (p = 1 x 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 x 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 x 10-7). In conclusion, DHCR7 rs12785878 and GC rs4588, but not CYP2R1 rs10741657, are significantly associated with vitamin D levels. When the 3 variants were considered together as GRS, a strong association with vitamin D levels and vitamin D insufficiency was observed, thus providing robust evidence that genes involved in vitamin D metabolism modulate serum vitamin D in T2D

Characterization of Glial Cell Models and In Vitro Manipulation of the Neuregulin1/ErbB System

The neuregulin1/ErbB system plays an important role in Schwann cell behavior both in normal and pathological conditions. Upon investigation of the expression of the neuregulin1/ErbB system in vitro, we explored the possibility to manipulate the system in order to increase the migration of Schwann cells, that play a fundamental role in the peripheral nerve regeneration. Comparison of primary cells and stable cell lines shows that both primary olfactory bulb ensheathing cells and a corresponding cell line express ErbB1-ErbB2 and neuregulin1, and that both primary Schwann cells and a corresponding cell line express ErbB2-ErbB3, while only primary Schwann cells express neuregulin1. To interfere with the neuregulin1/ErbB system, the soluble extracellular domain of the neuregulin1 receptor ErbB4 (ecto-ErbB4) was expressed in vitro in the neuregulin1 expressing cell line, and an unexpected increase in cell motility was observed. In vitro experiments suggest that the back signaling mediated by the transmembrane neuregulin1 plays a role in the migratory activity induced by ecto-ErbB4. These results indicate that ecto-ErbB4 could be used in vivo as a tool to manipulate the neuregulin1/ErbB system

Effect of Local Delivery of GDNF Conjugated Iron Oxide Nanoparticles on Nerve Regeneration along Long Chitosan Nerve Guide

Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half‐life of few minutes. In previous studies, it was demonstrated that conjugation of various neurotrophic factors to iron oxide nanoparticles (IONP) led to stabilization of the growth factors and to the extension of their biological activity compared to the free factors. In vitro studies performed on organotypic dorsal root ganglion (DRG) cultures seeded in NVR gel (composed mainly of hyaluronic acid and laminin) revealed that the glial cell–derived neurotrophic factor (GDNF) conjugated to IONP‐enhanced early nerve fiber sprouting and accelerated the onset and progression of myelin significantly earlier than the free GDNF and other free and conjugated factors. The present article summarizes results of in vivo study, aimed to test the effect of free versus conjugated GDNF on regeneration of the rat sciatic nerve after a severe segment loss. We confirmed that nerve device enriched with a matrix with GDNF gives more successful results in term of regeneration and functional recovery in respect to the hollow tube; moreover, there are no detectable differences between free versus conjugated GDNF