Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus

We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c]>= 7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.Peer reviewe

Frustration driven C-4 symmetric orders in a naturally heterostructured superconductor Sr2VO3FeAs

A subtle balance between competing interactions in iron-based superconductors (FeSCs) can be tipped by additional interfacial interactions in a heterostructure, often inducing exotic phases with unprecedented properties. Particularly when the proximity-coupled layer is magnetically active, rich phase diagrams are expected in FeSCs, but this has not been explored yet. Here, using high-accuracy 75As and 51V nuclear magnetic resonance measurements, we investigate an electronic phase that emerges in the FeAs layer below T0 ~ 155 K of Sr2VO3FeAs, a naturally assembled heterostructure of an FeSC and a Mottinsulating vanadium oxide. We find that frustration of the otherwise dominant Fe stripe and V Neel fluctuations via interfacial coupling induces a charge/orbital order in the FeAs layers, without either static magnetism or broken C4 symmetry, while suppressing the Neel antiferromagnetism in the SrVO3 layers. These findings demonstrate that the magnetic proximity coupling stabilizes a hidden order in FeSCs, which may also apply to other strongly correlated heterostructures. © The Author(s) 20171111sciescopu

Frustration-driven C-4 symmetric order in a naturally-heterostructured superconductor Sr2VO3FeAs

A subtle balance between competing interactions in iron-based superconductors (FeSCs) can be tipped by additional interfacial interactions in a heterostructure, often inducing exotic phases with unprecedented properties. Particularly when the proximity-coupled layer is magnetically active, rich phase diagrams are expected in FeSCs, but this has not been explored yet. Here, using high-accuracy 75As and 51V nuclear magnetic resonance measurements, we investigate an electronic phase that emerges in the FeAs layer below T0 ~ 155 K of Sr2VO3FeAs, a naturally assembled heterostructure of an FeSC and a Mottinsulating vanadium oxide. We find that frustration of the otherwise dominant Fe stripe and V Neel fluctuations via interfacial coupling induces a charge/orbital order in the FeAs layers, without either static magnetism or broken C4 symmetry, while suppressing the Neel antiferromagnetism in the SrVO3 layers. These findings demonstrate that the magnetic proximity coupling stabilizes a hidden order in FeSCs, which may also apply to other strongly correlated heterostructures.112Nsciescopu

Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome

Triple A syndrome is a rare genetic disorder caused by mutations in the achalasia-addisonianism-alacrima syndrome (AAAS) gene which encodes a tryptophan aspartic acid (WD) repeat-containing protein named alacrima-achalasia-adrenal insufficiency neurologic disorder (ALADIN). Northern blot analysis shows that the 2.1 kb AAAS mRNA is expressed in various tissues with stronger expression in testis and pancreas. We show that human ALADIN is a protein with an apparent molecular weight of 60 kDa, and expressed in the adrenal gland, pituitary gland and pancreas. Furthermore, biochemical analysis using anti-ALADIN antibody supports the previous finding of the localization of ALADIN in the nuclear membrane. The mutations S544G and S544X show that alteration of S544 residue affects correct targeting of ALADIN to the nuclear membrane

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo