Titratable fixed-ratio combination of insulin glargine plus lixisenatide: A simplified approach to glycemic control in type 2 diabetes mellitus

Approximately 50% of patients with type 2 diabetes mellitus (T2DM) do not achieve glycemic targets and require treatment intensification. A fixed-ratio combination of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin, such as lixisenatide with insulin glargine (iGlarLixi), exploits the complementary mechanisms of action of each component to address hyperglycemia while mitigating potential adverse events (AEs). The iGlarLixi dose is titrated considering the effect of basal insulin on fasting plasma glucose, and the fixed-ratio combination ensures that the lixisenatide dose never exceeds 20 μg/day. We describe the characteristics of iGlarLixi therapy, based on the LixiLan clinical program, and provide guidance on the characteristics of patients likely to benefit from such treatment in routine clinical practice. In the phase III LixiLan trials, iGlarLixi resulted in significantly greater reductions in glycated hemoglobin (HbA1c), better achievement of HbA1c targets, less glycemic variability versus insulin glargine, lixisenatide or GLP-1 RA alone, and was associated with weight control, less hypoglycemia versus insulin glargine, and fewer GI AEs versus lixisenatide. Findings were consistent regardless of age, diabetes duration, and baseline HbA1c. The efficacy, safety, and convenient once-daily administration schedule of iGlarLixi make it a valuable treatment option for patients with T2DM requiring treatment intensification

The impact of corporate governance on the market value of financial institutions : empirical evidences from Italy

This paper analyses how the quality of the Corporate Governance system impacts on the market value of Italian financial institution listed on Italian Stock Exchange. As implementing a good Corporate Governance is costly, this study is useful to verify if the investment is worth its cost. This work wants to fill a gap in literature: in fact there are few studies that have focused on financial institutions despite the central role that they hold in the real economy, especially in Italy where the enterprises are highly dependent on the banking system for their financing needs

Accountability and music: accounting, emotions and responses to the 1913 concert for Giuseppe Verdi

Purpose: This study aims to explore the engagement between accounting and music in the social and relational construction of accountability. The authors conceive this construction as a dynamic and recursive interplay between the giving of different accounts and the responses that these accounts provoke. The authors investigate the emotional dimension of this interplay, as it is also triggered by music, feeding back into how accountability is constructed and evolves over time. Design/methodology/approach: This study relies upon a historical analysis of archival and secondary sources about the main music concert organized in 1913 by the founder of “Accademia Chigiana”, one of the leading music academies in Italy. The concert celebrated the first centenary of the birth of Giuseppe Verdi, a worldwide famous Italian music composer, and icon of Italian national sentiment. Findings: This study shows that music and accounting were profoundly intertwined in the social and relational construction of accountability for the 1913 concert. Accountability evolved through different accounts, also linked to music, and the complex emotional reactions these accounts provoked in the audiences, citizens, media and institutions, leading to always further responses and accounts in the ongoing construction of accountability. Originality/value: This study extends prior literature on the chameleonic nature of accountability, as well as on its relational and emotional dimensions. The study shows that accountability is relationally constructed and evolves over time through the giving of accounts and the emotional reaction they provoke from others, feeding into further responses and accounts of the accountable subject. The authors show how the chameleonic nature of accountability permeates not only the accounts and the relations of accountability but also the subjects giving and demanding the accounts: these subjects change as chameleons through their interactions and emotions, feeding into the dynamic construction of accountability. The authors also show how arts, like music, can participate in the chameleonic nature of accountability and of its subjects, precisely by engaging with their emotional reactions and responses

11 beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle

OBJECTIVE: Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. \ud RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. \ud RESULTS: Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer$^{307}$ insulin receptor substrate (IRS)-1. 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer$^{307}$ IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer$^{307}$ IRS1 decreased and pThr$^{308}$ Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression.\ud CONCLUSIONS: Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer$^{307}$ IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11beta-HSD1 inhibition decreases pSer$^{307}$ IRS1, increases pThr$^{308}$ Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action

iGlarLixi effectively reduces residual hyperglycaemia in patients with type 2 diabetes on basal insulin: A post hoc analysis from the LixiLan-L study

Globally, nearly half of patients with type 2 diabetes (T2D) do not successfully achieve target HbA1c with basal insulin, despite meeting fasting plasma glucose (FPG) targets. In this post hoc analysis of the LixiLan-L study, we determined whether iGlarLixi, a fixed-ratio combination of insulin glargine Gla-100 (iGlar) and the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi), addresses the challenge of reducing residual hyperglycaemia in patients with T2D. In LixiLan-L, a randomized, open-label study, 1018 patients with T2D on basal insulin for ≥6 months ± oral antidiabetes drugs entered a 6-week run-in period, during which they were switched to and/or optimized for a daily dose of iGlar while continuing only metformin. Following the run-in period, 736 patients were then randomized to receive iGlarLixi or were continued on iGlar for 30 weeks ± metformin. Residual hyperglycaemia was defined as HbA1c ≥ 7.0% despite FPG of <140 mg/dL. The proportion of patients with residual hyperglycaemia was similar in both treatment arms at screening (~~42%), and increased after the run-in period (~~62%). After 30 weeks, the proportion of patients with residual hyperglycaemia declined to 23.8% in the iGlarLixi versus 47.1% in the iGlar arm (P <.0001). The proportion of patients achieving both HbA1c (<7.0%) and FPG (<140 mg/dL) targets was higher in the iGlarLixi compared with the iGlar arm (50.3% vs. 27.4%, respectively; P <.0001). iGlarLixi effectively reduces residual hyperglycaemia in patients with T2D on basal insulin therapy

COVID-19: not a contraindication for surgery in patients with proximal femur fragility fractures.

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The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor

Reactive oxygen species (ROS) are highly reactive chemical species containing oxygen, controlled by both enzymatic and nonenzymatic antioxidant defense systems. In the heart, ROS play an important role in cell homeostasis, by modulating cell proliferation, differentiation, and excitation-contraction coupling. Oxidative stress occurs when ROS production exceeds the buffering capacity of the antioxidant defense systems, leading to cellular and molecular abnormalities, ultimately resulting in cardiac dysfunction. In this review, we will discuss the physiological sources of ROS in the heart, the mechanisms of oxidative stress-related myocardial injury, and the implications of experimental studies and clinical trials with antioxidant therapies in cardiovascular diseases

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET)

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed