COVID-19 and Cardiovascular Comorbidities.

The emergence of a new coronavirus - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - has resulted in a global pandemic. The associated coronavirus disease 2019 (COVID-19) has resulted in a high number of death worldwide. Observational studies and case reports have provided insights that older age and the presence of chronic diseases is frequently associated with a higher COVID-19 severity. These individuals also seem to have a higher risk of mortality due to COVID-19. In this review we provide insights into the impact chronic diseases associated with the cardiovascular system, such as obesity, diabetes mellitus, hypertension and cardiovascular disease might have on SARS-CoV-2 infection and COVID-19. Additionally we review recommendations and guidance's of international scientific associations and discuss which key learnings might be of importance for the future.

The burden of type 2 diabetes in Europe: Current and future aspects of insulin treatment from patient and healthcare spending perspectives.

Due to the progressive nature of type 2 diabetes (T2DM), initiation of insulin therapy is very likely in the disease continuum. This article aims at highlighting the current situation with regard to insulin therapy in people with T2DM in Europe and at presenting the associated unmet need. Challenges for both people with T2DM and healthcare professionals include clinical inertia also derived from fear of hypoglycaemia, weight gain and injections as well as increased need for a comprehensive diabetes management. We compare national and international guidelines and recommendations for the initiation and intensification of insulin therapy with the real-world situation in six European countries, demonstrating that glycaemic targets are only met in a minority of people with T2DM on insulin therapy. Furthermore, this work evaluates currently recorded numbers of people with T2DM treated with insulin in Europe, the proportion not achieving the stated glycaemic targets and thus in need to enhance insulin therapy e.g. by a change in means of insulin delivery including, but not limited to, insulin pens, wearable mealtime insulin delivery patches, patch pumps, and conventional insulin pumps with continuous subcutaneous insulin infusion.

Budget Impact of Improved Diabetes Management by Utilization of Glucose Meters With a Color-Range Indicator-Comparison of Five European Healthcare Systems.

BACKGROUND AND AIM: Costs for the treatment of diabetes and its comorbidities are a major international issue. A recent randomized clinical trial showed that the introduction of color range indicator (CRI)-based glucose meters (GMs) positively affects the HbA1c of patients with type 1 and type 2 diabetes, when compared to GMs without a CRI. This budget impact analysis aimed to translate this beneficial effect of CRI-based GMs, OneTouch Verio Flex and OneTouch Verio, into potential monetary impact for the healthcare systems of five European countries, Germany, Spain, Italy, France, and the United Kingdom. MATERIAL AND METHODS: Data from a randomized controlled trial, evaluating the effect of CRI-based GMs, were used to estimate the ten-year risk of patients for fatal myocardial infarction (MI) as calculated by the UK Prospective Diabetes Study (UKPDS) risk engine. On the basis of assessed risks for MI, the potential monetary impact for the healthcare systems in five European countries was modeled. RESULTS: Based on a mean HbA1c reduction of 0.36%, as demonstrated in a randomized controlled trial, the UKPDS risk engine estimated a reduction of 2.4% of the ten-year risk of patients for fatal MI. When applied to our economic model, substantial potential cost savings for the healthcare systems of five European countries were calculated: €547 472 (France), €9.0 million (Germany), €6.0 million (Italy), €841 799 (Spain), and €421 069 (United Kingdom) per year. CONCLUSION: Improving metabolic control in patients with diabetes by the utilization of CRI-based GMs may have substantial positive effects on the expenditure of the healthcare systems of several European countries.

Patient-centred care in type 2 diabetes mellitus - Key aspects of PDM-ProValue are reflected in the 2018 ADA/EASD consensus report.

In 2018, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) published a consensus report on the management of hyperglycaemia in type 2 diabetes, recommending, amongst others, a patient-centred decision cycle to prevent complications and optimise quality of life. The PDM-ProValue study program which focused on the assessment of integrated personalised diabetes management provided evidence for the efficacy of its implementation. In this comparative review, we identified the standardised decision cycle as well as individualised patient assessment as the overarching elements of the ADA/EASD consensus report and the PDM-ProValue study. The decision cycle, investigated in PDM-ProValue and similarly recommended by the 2018 ADA/EASD consensus report, can benefit diabetes management in persons with type 2 diabetes. This is reflected in improved glycaemic control as well as patient and physician communication and satisfaction.

Pan-European Economic Analysis to Identify Cost Savings for the Health Care Systems as a Result of Integrating Glucose Monitoring Based Telemedical Approaches Into Diabetes Management.

BACKGROUND: Self-monitoring of blood glucose supported by the diabetes-app OneTouch Reveal® has demonstrated to improve HbA1c. We aimed at analyzing costs savings related the integration of telemedical features into diabetes management. METHODS: Data from a randomized controlled trial were used to assess the 10-year risk of patients for fatal myocardial infarction (MI). On the basis of this risk assessments-also related to a 5% or 10% reduction of hypoglycemic episodes-cost savings for the health care systems of five European countries-France, Germany, Italy, Spain, and the United Kingdom-were modeled. RESULTS: HbA1c reduction of 0.92% in insulin-treated type 2 diabetes patients (T2DM) was associated with a 2.3% decreased 10-year risk for fatal MI. In combination with a 10% reduction of hypoglycemic events this risk reduction led to cost savings of €16.1 million (France), €57.8 million (Germany), €30.9 million (Italy), €23.8 million (Spain), and €5.8 million (UK), considering all insulin-treated T2DM patients in the respective countries. CONCLUSION: Improving metabolic control and thus risk for comorbidities like MI by combining the glucose meter with CRI with telemedical features has the potential to reduce costs for European health care systems.

PDM-ProValue meets cardiovascular outcome trials in diabetes.

Novel studies have increased our knowledge regarding optimal treatment options in diabetes. Key studies that have broadened our knowledge about optimal treatment options in diabetes in recent years are cardiovascular outcome trials (CVOTs) and studies investigating aspects of digitalisation and monitoring of glucose (e.g. PDM-ProValue). We aimed at highlighting similarities between the two important pillars for a successful diabetes management. We emphasise the need for a consideration of both approaches in future clinical trial designs and protocols.

Modeling of Diabetes and Its Clinical Impact.

Understanding all aspects of diabetes treatment is hindered by the complexity of this chronic disease and its multifaceted complications and comorbidities, including social and financial impacts. In vivo studies as well as clinical trials provided invaluable information for unraveling not only metabolic processes but also risk estimations of, for example, complications. These approaches are often time- and cost-consuming and have frequently been supported by simulation models. Simulation models provide the opportunity to investigate diabetes treatment from additional viewpoints and with alternative objectives. This review presents selected models focusing either on metabolic processes or risk estimations and financial outcomes to provide a basic insight into this complex subject. It also discusses opportunities and challenges of modeling diabetes.

Improvement of Metabolic Control and Diabetes Management in Insulin-Treated Patients Results in Substantial Cost Savings for the German Health System.

BACKGROUND: Self-monitoring of blood glucose (SMBG) using the ColourSure™ Technology to visualize target range showed improvement of metabolic control and overall diabetes self-management in insulin-treated patients. This economic analysis aimed to identify cost savings for the German health system resulting from an HbA1c reduction due to the utilization of user-friendly glucose meters. METHODS: Patient data from a recently published observational study on SMBG were used for risk evaluations using the UKPDS risk engine. These values were integrated in an economic analysis regarding costs of myocardial infarctions (MIs) related to diabetes for the German health system. Based on an earlier assessment these calculations were combined with a 10% reduction of severe hypoglycemic episodes. In the current study, 0% severe hypoglycemic episodes were observed. RESULTS: An HbA1c reduction of 0.69% over 6 months was associated with a 3% decreased risk of MI in 10 years. In this model the decrease led to cost savings of €4.90 per patient-year. Considering 2.3 million insulin-treated patients in Germany, this 3% reduction of MI could result in annual savings of €11.27 million. Combining this with a 10% reduction in severe hypoglycemic events, the cost savings would increase to €30.61 per patient-year or €70.4 million for 2.3 million insulin-treated patients in Germany. CONCLUSION: The improvement of metabolic control and diabetes self-management that was achieved with the ColourSure™ Technology has the potential to generate substantial cost savings for the German health system underlining the importance of user-friendly methods for SMBG.

Myotube migration to cover and shape the testis of Drosophila depends on Heartless, Cadherin/Catenin, and myosin II.

During Drosophila metamorphosis, nascent testis myotubes migrate from the prospective seminal vesicle of the genital disc onto pupal testes and then further to cover the testes with multinucleated smooth-like muscles. Here we show that DWnt2 is likely required for determination of testis-relevant myoblasts on the genital disc. Knock down of fibroblast growth factor receptor (FGFR) heartless by RNAi and a dominant-negative version revealed multiple functions of Heartless, namely regulation of the amount of myoblasts on the genital disc, connection of seminal vesicles and testes, and migration of muscles along the testes. Live imaging indicated that the downstream effector Stumps is required for migration of testis myotubes on the testis towards the apical tip. After myoblast fusion, myosin II is needed for migration of nascent testis myotubes, in which Thisbe-dependent fibroblast growth factor (FGF) signaling is activated. Cadherin-N is essential for connecting these single myofibers and for creating a firm testis muscle sheath that shapes and stabilizes the testis tubule. Based on these results, we propose a model for the migration of testis myotubes in which nascent testis myotubes migrate as a collective onto and along the testis, dependent on FGF-regulated expression of myosin II.

A new level of plasticity: Drosophila smooth-like testes muscles compensate failure of myoblast fusion.

The testis of Drosophila resembles an individual testis tubule of mammals. Both are surrounded by a sheath of smooth muscles, which in Drosophila are multinuclear and originate from a pool of myoblasts that are set aside in the embryo and accumulate on the genital disc later in development. These muscle stem cells start to differentiate early during metamorphosis and give rise to all muscles of the inner male reproductive system. Shortly before the genital disc and the developing testes connect, multinuclear nascent myotubes appear on the anterior tips of the seminal vesicles. Here, we show that adhesion molecules are distinctly localized on the seminal vesicles; founder cell (FC)-like myoblasts express Dumbfounded (Duf) and Roughest (Rst), and fusion-competent myoblast (FCM)-like cells mainly express Sticks and stones (Sns). The smooth but multinuclear myotubes of the testes arose by myoblast fusion. RNAi-mediated attenuation of Sns or both Duf and Rst severely reduced the number of nuclei in the testes muscles. Duf and Rst probably act independently in this context. Despite reduced fusion in all of these RNAi-treated animals, myotubes migrated onto the testes, testes were shaped and coiled, muscle filaments were arranged as in the wild type and spermatogenesis proceeded normally. Hence, the testes muscles compensate for fusion defects so that the myofibres encircling the adult testes are indistinguishable from those of the wild type and male fertility is guaranteed.