Making Use of Comparable Health Data to Improve Quality of Care and Outcomes in Diabetes: The EUBIROD Review of Diabetes Registries and Data Sources in Europe.

Background: Registries and data sources contain information that can be used on an ongoing basis to improve quality of care and outcomes of people with diabetes. As a specific task of the EU Bridge Health project, we carried out a survey of diabetes-related data sources in Europe.

Objectives: We aimed to report on the organization of different sources of diabetes information, including their governance, information infrastructure and dissemination strategies for quality control, service planning, public health, policy and research.

Assessing data protection and governance in health information systems: a novel methodology of Privacy and Ethics Impact and Performance Assessment (PEIPA).

Background: Data processing of health research databases often requires a Data Protection Impact Assessment to evaluate the severity of the risk and the appropriateness of measures taken to comply with the European Union (EU) General Data Protection Regulation (GDPR). We aimed to define and apply a comprehensive method for the evaluation of privacy, data governance and ethics among research networks involved in the EU Project Bridge Health.

Methods: Computerised survey among associated partners of main EU Consortia, using a targeted instrument designed by the principal investigator and progressively refined in collaboration with an international advisory panel.

An in-depth assessment of diabetes-related lower extremity amputation rates 2000-2013 delivered by twenty-one countries for the data collection 2015 of the Organization for Economic Cooperation and Development (OECD).

Background: International comparisons of diabetes-related lower extremity amputation rates are still hampered by different criteria used for data collection and analysis. We aimed to evaluate trends and variation of major/minor amputations, using agreed definitions adopted by the Organization for Economic Cooperation and Development in 2015.

Methods: Direct age-sex standardized rates were calculated per 100,000 subjects per year between 2000 and 2013, using major/minor amputations with diabetes diagnosis as numerators and the total population or number of people with diabetes as denominators.

Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study).

Aim: To estimate type 2 diabetes mellitus (T2DM) prevalence in Russian adults.

Methods: NATION is a national, epidemiological, cross-sectional study, conducted in Russia. In adults (aged 20-79 years), recruitment was stratified by age, sex, geographic region and settlement type to obtain a representative sample.

Low-grade inflammation, diet composition and health: current research evidence and its translation.

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe).

Cross-border flow of health information: is 'privacy by design' enough? Privacy performance assessment in EUBIROD.

Background: The EUBIROD project aims to perform a cross-border flow of diabetes information across 19 European countries using the BIRO information system, which embeds privacy principles and data protection mechanisms in its architecture (privacy by design). A specific task of EUBIROD was to investigate the variability in the implementation of the EU Data Protection Directive (DPD) across participating centres.

Methods: Compliance with privacy requirements was assessed by means of a specific questionnaire administered to all participating diabetes registers.

Cost-effectiveness of pioglitazone in type 2 diabetes patients with a history of macrovascular disease: a German perspective.

Background: The aim of this study was to project health-economic outcomes relevant to the German setting for the addition of pioglitazone to existing treatment regimens in patients with type 2 diabetes, evidence of macrovascular disease and at high risk of cardiovascular events.

Methods: Event rates corresponding to macrovascular outcomes from the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) study of pioglitazone were used with a modified version of the CORE Diabetes Model to simulate outcomes over a 35-year time horizon. Direct medical costs were accounted from a healthcare payer perspective in year 2005 values.

Treatment of type 2 diabetes with combined therapy: what are the pros and cons?

Type 2 diabetes is a progressive syndrome that evolves toward complete insulin deficiency during the patient's life. A stepwise approach for its treatment should be tailored according to the natural course of the disease, including adding insulin when hypoglycemic oral agent failure occurs. Treatment with insulin alone should eventually be considered in a relevant number of cases.

PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study.

Patients with type 2 diabetes face an increased risk of macrovascular disease compared to those without. Significant reductions in the risk of major cardiovascular events can be achieved with appropriate drug therapy, although patients with type 2 diabetes remain at increased risk compared with non-diabetics. The thiazolidinedione, pioglitazone, is known to offer multiple, potentially antiatherogenic, effects that may have a beneficial impact on macrovascular outcomes, including long-term improvements in insulin resistance (associated with an increased rate of atherosclerosis) and improvement in the atherogenic lipid triad (low HDL-cholesterol, raised triglycerides, and a preponderance of small, dense LDL particles) that is observed in patients with type 2 diabetes.

Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type 1 diabetic patients.

Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear. It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients.

Clinical validation of a new control-oriented model of insulin and glucose dynamics in subjects with type 1 diabetes.

Background: The development of an artificial pancreas requires an accurate representation of diabetes pathophysiology to create effective and safe control systems for automatic insulin infusion regulation. The aim of the present study is the assessment of a previously developed mathematical model of insulin and glucose metabolism in type 1 diabetes and the evaluation of its effectiveness for the development and testing of control algorithms.

Methods: Based on the already existing "minimal model" a new mathematical model was developed composed of glucose and insulin submodels.

Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08).

Objective: PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) enrolled patients with type 2 diabetes and preexisting cardiovascular disease. These patients were at high risk for heart failure, so any therapeutic benefit could potentially be offset by risk of associated heart failure mortality. We analyzed the heart failure cases to assess the effects of treatment on morbidity and mortality after reports of serious heart failure.

Quality and behavior of glimepiride generics versus amaryl under stressed conditions.

Background: The use of generic versions of drugs, such as those for glimepiride [Amaryl, Amarel, Solosa (sanofi-aventis, Paris, France)], a third-generation sulfonylurea, can reduce healthcare costs. However, the quality and performance of these generics should be carefully evaluated.

Methods: We compared the quality and behavior of 23 marketed generic forms with Amaryl (all 2 mg) under stressed conditions.

The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study.

Objectives: This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI).

Background: People with type 2 diabetes have an increased incidence of MI compared with the general population. Those with diabetes and MI have a worse prognosis than nondiabetic patients with cardiovascular disease.

Control oriented model of insulin and glucose dynamics in type 1 diabetics.

The aim of the study was to realize a mathematical model of insulin-glucose relationship in type I diabetes and test its effectiveness for the design of control algorithms in external artificial pancreas. A new mathematical model, divided into glucose and insulin sub-models, was developed from the so-called "minimal model". The key feature is the representation of insulin sensitivity so as to permit the personalisation of the parameters.

Changing targets in the treatment of type 2 diabetes.

Background: While correction of hyperglycemia remains central to the management of type 2 diabetes, current management approaches address an integrated constellation of disorders that predispose patients to the risk of microvascular and macrovascular complications.

Scope: This paper reviews glycemic control targets and associated cardiovascular disease risk management in type 2 diabetes, as recommended by the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the UK National Institute for Clinical Excellence (NICE). It is based upon MEDLINE literature searches from January 1995 to April 2006.

National survey on the execution of the oral glucose tolerance test (OGTT) in a representative cohort of Italian laboratories.

Background: Recently revised diagnostic criteria for diabetes mellitus and the lack of universal agreement on the methodology for the screening and diagnosis of gestational diabetes mellitus (GDM) still generate inconsistency in execution of the oral glucose tolerance test (OGTT). The aim of the present survey was to evaluate the adherence of Italian laboratories to the internationally accepted guidelines in carrying out the OGTT for the diagnosis of diabetes in the general population and for the screening of GDM.

Methods: A questionnaire was designed to investigate the following issues related to the OGTT: 1) the relationship between laboratories and diabetes centres for the definition of standard protocols; 2) the amount of glucose administered; 3) the number and timing of blood samples; 4) the procedures used for the screening and diagnosis of GDM; and 5) reference to WHO guidelines for the interpretation of the results.

Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.

Background: Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes.

The costs of type 2 diabetes mellitus in Italy: a CODE-2 sub-study.

Aim: To estimate the direct, indirect, and intangible costs associated with type 2 diabetes mellitus in Italy in 1998. To evaluate the economic impact of diabetic complications, and to investigate drug treatment patterns and associated costs in patients with type 2 diabetes.

Methods: The Italian arm of an international study (COsts of Diabetes in Europe--Type 2 [CODE-2], a descriptive, cross-sectional survey) was set up to collect information retrospectively by means of questionnaires from a sample of 1263 patients.

Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes.

Objective: Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin.

Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes.

A nonlinear model predictive controller has been developed to maintain normoglycemia in subjects with type 1 diabetes during fasting conditions such as during overnight fast. The controller employs a compartment model, which represents the glucoregulatory system and includes submodels representing absorption of subcutaneously administered short-acting insulin Lispro and gut absorption. The controller uses Bayesian parameter estimation to determine time-varying model parameters.

The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients.

Objective: The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) assesses the effect of pioglitazone, a peroxisome proliferator-activated receptor agonist, with anti-inflammatory and vascular properties, on the secondary prevention of macrovascular events in type 2 diabetes.

Research Design And Methods: PROactive is an on-going randomized, double-blind outcome study in patients with type 2 diabetes managed with diet and/or oral blood glucose-lowering drugs (combination of oral agents with insulin is permitted) who have a history of macrovascular disease. Patients are randomized to receive pioglitazone (forced titration from 15 to 30 to 45 mg, depending on tolerability) or placebo in addition to existing therapy.

Closing the loop: the adicol experience.

The objective of the project Advanced Insulin Infusion using a Control Loop (ADICOL) was to develop a treatment system that continuously measures and controls the glucose concentration in subjects with type 1 diabetes. The modular concept of the ADICOL's extracorporeal artificial pancreas consisted of a minimally invasive subcutaneous glucose system, a handheld PocketPC computer, and an insulin pump (D-Tron, Disetronic, Burgdorf, Switzerland) delivering subcutaneously insulin lispro. The present paper describes a subset of ADICOL activities focusing on the development of a glucose controller for semi-closed-loop control, an in silico testing environment, clinical testing, and system integration.

Glimepiride in type 2 diabetes mellitus: a review of the worldwide therapeutic experience.

Background: Sulfonylureas (SUs) have been used for many years as first-line therapy for patients with type 2 diabetes mellitus whose blood glucose levels have not been effectively controlled by diet and exercise alone. Glimepiride is a once-daily SU that was introduced in 1995. Since then, a considerable body of evidence has been amassed regarding its use in type 2 diabetes.