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  • Kofoed posted an update 9 months, 1 week ago

    The recent reported Vildagliptin Efficacy in combination with metfoRmin For earlY treatment of T2DM (VERIFY) study results have provided significant new evidence confirming long-term glycaemic durability and tolerability of a specific early combination in the management of newly diagnosed, treatment-naïve patients worldwide. These results have also contributed to changes in clinical treatment guidelines and standards of care while clinical implementation and individualised treatment decisions based on VERIFY results might face barriers beyond the existing scientific evidence.The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (-0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was -0.9%±1.2% (P less then 0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was -0.7%±1.2% (P less then 0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.

    To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term durable glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

    In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (<7.0%) <3, 3 to 6 (early achievement group), and ≥6 months (late achievement group). Risks of microvascular complications including diabetic retinopathy, nephropathy, and neuropathy as well as macrovascular events including ischemic heart disease, ischemic stroke, and peripheral arterial disease were assessed by multivariable Cox proportional hazards analysis.

    During a median follow-up of 6.53 years, 66 microvascular and 14 macrovascular events occurred. Maintenance of durable glycemic control over 6 years was more likely in the early achievement groups than in the late achievement group (34.5%, 30.0%, and 16.1% in <3, 3 to 6, and ≥6 months, respectively, P=0.039). Early target HbA1c achievement was associated with lower risk of composite diabetic complications (adjusted hazard ratio [HR, 0.47; 95% confidence interval [CI], 0.26 to 0.86 in <3 months group) (adjusted HR, 0.50; 95% CI, 0.23 to 1.10 in 3 to 6 months group, in reference to ≥6 months group). Similar trends were maintained for risks of microvascular and macrovascular complications, although statistical significance was not reached for macrovascular complications.

    Early target HbA1c achievement was associated with long-term durable glycemic control and reduced risk of diabetic complications in newly diagnosed T2DM.

    Early target HbA1c achievement was associated with long-term durable glycemic control and reduced risk of diabetic complications in newly diagnosed T2DM.Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage.We investigated the distribution of Dermacentor spp. and their infection by zoonotic bacteria causing SENLAT (scalp eschar neck lymphadenopathy) in Turin province, northwestern Italy. We collected ticks in a mountain and in a periurban park, from vegetation and different animal sources, and we sampled tissues from wild boar. Dermacentor marginatus (n = 121) was collected in both study areas, on vegetation, humans, and animals, while D. reticulatus (n = 13) was exclusively collected on wild boar from the periurban area. selleck chemicals Rickettsia slovaca and Candidatus Rickettsia rioja infected 53.1% of the ticks, and R. slovaca was also identified in 11.3% of wild boar tissues. Bartonella spp. and Francisella tularensis were not detected, however, Francisella-like endosymbionts infected both tick species (9.2%). Our findings provide new insights on the current distribution of Dermacentor spp. and their infection with a spotted-fever group rickettsiae in the Alps region. Wild boar seem to play a major role in their eco-epidemiology and dispersion in the study area.

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