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. Methods: Survey using a structured questionnaire to collect targeted data from a network of collaborating institutions managing registries and data sources in 17 countries in the year 2017. Results: The 18 data sources participating in the study were most frequently academic centres (44.4%), national (72.2%), targeting all types of diabetes (61.1%) covering no more than 10% of the target population (44.4%). Although population-based in over a quarter of cases (27.8%), sources relied predominantly on provider-based datasets (38.5%), fewer using administrative data (16.6%). Data collection was continuous in the majority of cases (61.1%), but 50% could not perform data linkage. Public reports were more frequent (72.2%) as well as quality reports (77.8%), but one third did not provide feedback to policy and only half published ten or more peer reviewed papers during the last 5 years. Conclusions: The heterogeneous implementation of diabetes registries and data sources hampers the comparability of quality and outcomes across Europe. Best practices exist but need to be shared more effectively to accelerate progress and deliver equitable results for people with diabetes.

Laboratory Production of Equine Embryos.

Assisted reproduction technologies (ART) are well developed in humans and cattle and are gaining momentum also in the equine industry because of the fact that the mare does not respond to superovulation but can donate large numbers of oocytes through ovum pick up (OPU). After collection, the oocytes can be fertilized by intracytoplasmic sperm injection (ICSI) using a variety of stallion semen samples, even of poor quality, and the resulting embryos can establish high pregnancy rates after cryopreservation and transfer. The discoveries that equine oocytes can be held at room temperature without loss of viability and that an increase in vitro maturation time can double the number of embryos produced are fueling the uptake of the OPU technique by several clinics that are shipping oocytes of their client's mares to specialized ICSI laboratories for embryo production and freezing. In this article, we present a retrospective analysis of 10 years of work at Avantea with a special focus on the last 3 years. Based on our data, an average production of 1.7 to 2 embryos per OPU-ICSI procedure can be obtained from warmblood donor mares with a pregnancy rate of 70% and a foaling rate in excess of 50%. OPU-ICSI offers the added value of freezing embryos that allows the development of embryo commercialization worldwide to the benefit of top horse breeders who are endorsing this technology as never before.

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. Descriptive measures using the percentage of adoption of privacy, data governance and ethical principles as main endpoints were used for the analysis and interpretation of the results. RESULTS: A total of 15 centres provided relevant information on the processing of sensitive data from 10 European countries. Major areas of concern were noted for: data linkage (median, range of adoption: 45%, 30%-80%), access and accuracy of personal data (50%, 0%-100%) and anonymisation procedures (56%, 11%-100%). A high variability was noted in the application of privacy principles. CONCLUSIONS: A comprehensive methodology of Privacy and Ethics Impact and Performance Assessment was successfully applied at international level. The method can help implementing the GDPR and expanding the scope of Data Protection Impact Assessment, so that the public benefit of the secondary use of health data could be well balanced with the respect of personal privacy.

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. Longitudinal trends were investigated using generalized estimating equations. RESULTS: Twenty-one countries reported major amputations referred to the general population, showing a mean reduction from 10.8 to 7.5 per 100,000 (- 30.6%). Eleven countries also reported major amputations among people with diabetes, showing a mean reduction from 182.9 to 128.3 per 100,000 (- 29.8%). Minor amputations remained stable over the study period. Longitudinal trends showed a significant average annual decrease of - 0.19 per 100,000 in the general population (95% CI - 0.36 to - 0.02; p = .03) and - 4.52 per 100,000 among subjects with diabetes (95% CI - 6.09 to - 2.94; p < .001). The coefficient of variation of major amputation rates between countries was fairly high (64%-in the total population, 67% among people with diabetes). CONCLUSIONS: The study highlighted a clinically significant reduction of major amputations, in both the general population and among people with diabetes. The use of standardized definitions, while increasing the comparability of multinational data, highlighted remarkable differences between countries. These results can help identifying and sharing best practices effectively on a global scale.

Plica Syndrome and Bilateral Osteochondritis Dissecans.

A 13-year-old male basketball player presented to a direct-access physical therapy clinic with a chief complaint of left anterolateral knee pain that began 4 weeks earlier and was exacerbated after playing basketball. Following examination, the patient's primary care physician was consulted and recommended a magnetic resonance imaging (MRI) scan, which revealed infrapatellar plica synovialis and juvenile osteochondritis dissecans. J Orthop Sports Phys Ther 2019;49(10):762. doi:10.2519/jospt.2019.8922.

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. Recruitment was in public areas with high numbers of people. T2DM was diagnosed by glycated haemoglobin A1c (HbA1c) levels (diabetes: HbA1c ≥6.5% [≥48mmol/mol]; pre-diabetes: HbA1c ≥5.7 to <6.5% [≥39 to <48mmol/mol]). Socio-demographic and anthropometric data were collected. RESULTS: Blood samples from 26,620 subjects were available. Overall, 5.4% were diagnosed with T2DM (previously diagnosed: 2.5%; previously undiagnosed: 2.9%); 19.3% were pre-diabetic. T2DM prevalence increased with age (up to 70 years) and was higher among females than males (6.1% vs. 4.7%, p<0.001). The estimated proportion of subjects with pre-diabetes and T2DM tended to increase with increasing body mass index. T2DM prevalence was higher in rural versus urban populations (6.7% vs. 5.0%, p<0.001). CONCLUSION: In the Russian adult population, 19.3% had pre-diabetes, T2DM prevalence was 5.4%, and 54% of subjects with diabetes were previously undiagnosed. These results may help to develop a new T2DM predictive, preventative and management programme in Russia.

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). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled 'Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies'. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation-health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation-health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

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. Items included relevant issues e.g. patient consent, accountability of data custodian, communication (openness) and complaint procedures (challenging compliance), authority to disclose, accuracy, access and use of personal information, and anonymization. The identification of an ad hoc scoring system and statistical software allowed an overall quali-quantitative analysis and independent evaluation of questionnaire responses, automated through a dedicated IT platform ('privacy performance assessment'). RESULTS: A total of 18 diabetes registers from different countries completed the survey. Over 50% of the registers recorded a maximum score for accountability, openness, anonymization and challenging compliance. Low average values were found for disclosure and disposition, access, consent, use of personal information and accuracy. A high heterogeneity was found for anonymization, consent, accuracy and access. CONCLUSIONS: The novel method of privacy performance assessment realized in EUBIROD may improve the respect of privacy in each data source, reduce overall variability in the implementation of privacy principles and favour a sound and legitimate cross-border exchange of high quality data across Europe.

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. Germany specific costs were applied for patient treatment, hospitalization and management. Both costs and clinical benefits were discounted at 5.0% per annum. RESULTS: Over patient lifetimes pioglitazone treatment improved undiscounted life expectancy by 0.406 years and improved quality-adjusted life expectancy by 0.120 quality-adjusted life years (QALYs) compared to placebo. Direct medical costs (treatment plus complication costs) were marginally higher for pioglitazone treatment and calculation of the incremental cost-effectiveness ratio (ICER) produced a value of euro13,294 per QALY gained with the pioglitazone regimen versus placebo. Acceptability curve analysis showed that there was a 78.2% likelihood that pioglitazone would be considered cost-effective in Germany, using a "good value for money" threshold of euro50,000 per QALY gained. Sensitivity analyses showed that the results were most sensitive to changes in the simulation time horizon. After adjustment for the potential stabilization of pancreatic beta-cell function with pioglitazone treatment, the ICER was euro6,667 per QALY gained for pioglitazone versus placebo. CONCLUSION: The findings of this modelling analysis indicated that, for patients with a history of macrovascular disease, addition of pioglitazone to existing therapy reduces the long-term cumulative incidence of diabetes-complications at a cost that would be considered to represent good value for money in the German setting.

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. Experience has shown the protective effects of insulin on beta-cell survival and function, resulting in more stable metabolic control. On the contrary, treatment with most insulin secretagogues has been associated with increased beta-cell apoptosis, reduced responsiveness to high glucose, and impairment of myocardial function during ischemic conditions. In addition, macrovascular complications are associated with postprandial hyperglycemia, indicating the need for tight glycemic control. Insulin treatment, especially with rapid-acting analogs, has been demonstrated to successfully control postprandial glucose excursions. Finally, a reason for concern with regard to combined therapy is represented by the evidence that polipharmacy reduces compliance to the treatment regimen. This can be particularly relevant in patients with type 2 diabetes usually taking drugs for complications and for concomitant diseases with consequent deterioration not only of metabolic control but also of other conditions. In conclusion, therapy with insulin alone immediately after hypoglycemic oral agent failure may be a useful and safe therapeutic approach in type 2 diabetes.

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. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) study showed that pioglitazone can reduce the risk of secondary macrovascular events in a high-risk patient population with type 2 diabetes and established macrovascular disease. Here, we summarize the key results from the PROactive study and place them in context with other recent outcome trials in 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. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method, respectively. TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P = 0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P = 0.0156 and P = 0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis. Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events.

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. The glucose model includes the representation of peripheral uptake, hepatic uptake and release, and renal clearance. The insulin model describes the kinetics of exogenous insulin injected either subcutaneously or intravenously. The estimation of insulin sensitivity allows the model to personalize parameters to each subject. Data sets from two different clinical trials were used here for model validation through simulation studies. The first set had subcutaneous insulin injection, while the second set had intravenous insulin injection. The root mean square error between simulated and real blood glucose profiles (G(rms)) and the Clarke error grid analysis were used to evaluate the system efficacy. RESULTS: Results from our study demonstrated the model's capability in identifying individual characteristics even under different experimental conditions. This was reflected by an effective simulation as indicated by G(rms), and clinical acceptability by the Clarke error grid analysis, in both clinical data series. CONCLUSIONS: Simulation results confirmed the capacity of the model to faithfully represent the glucose-insulin relationship in type 1 diabetes in different circumstances.

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. RESEARCH DESIGN AND METHODS: PROactive was an outcome study in 5,238 patients randomized to pioglitazone or placebo. Patients with New York Heart Association Class II-IV heart failure at screening were excluded. A serious adverse event of heart failure was defined as heart failure that required hospitalization or prolonged a hospitalization stay, was fatal or life threatening, or resulted in persistent significant disability or incapacity. Heart failure risk was evaluated by multivariate regression. RESULTS: More pioglitazone (5.7%) than placebo patients (4.1%) had a serious heart failure event during the study (P = 0.007). However, mortality due to heart failure was similar (25 of 2,605 [0.96%] for pioglitazone vs. 22 of 2,633 [0.84%] for placebo; P = 0.639). Among patients with a serious heart failure event, subsequent all-cause mortality was proportionately lower with pioglitazone (40 of 149 [26.8%] vs. 37 of 108 [34.3%] with placebo; P = 0.1338). Proportionately fewer pioglitazone patients with serious heart failure went on to have an event in the primary (47.7% with pioglitazone vs. 57.4% with placebo; P = 0.0593) or main secondary end point (34.9% with pioglitazone vs. 47.2% with placebo; P = 0.025). CONCLUSIONS: Although the incidence of serious heart failure was increased with pioglitazone versus placebo in the total PROactive population of patients with type 2 diabetes and macrovascular disease, subsequent mortality or morbidity was not increased in patients with 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. Deblistered samples were stored at 60 degrees C for 21 days in order to mimic temperature-stressed conditions. Samples were analyzed at Days 0, 7, and 21 for content of active compound, levels of impurities, levels of residual solvent (Day 0 only), and dissolution profile, and results were compared against Amaryl specifications. RESULTS: Levels of the degradation product GS [corrected] were < or = 1% in all products at Day 0; however, GS levels [corrected] increased to above Amaryl specifications [corrected] in two generics at Day 7 (Dolcyl and GLA-DM) [corrected] and in four generics at Day 21 [Dolcyl, GLA-DM, glimepiride (Hanni), and glimepirida (Esterlina)] (Fig. 2) [corrected] Total levels of other impurities and levels of residual solvents were above Amaryl specifications (1,400 ppm, respectively) in two generics at Day 0. At Day 0, the dissolution of 12 generics (52%) failed to meet Amaryl specifications (>or=85% dissolved in 15 min); this trend was confirmed at Day 21. Overall, 74% (17 of 23) of the generics were not of equivalent quality or performance compared with Amaryl. CONCLUSIONS: This study indicates that a relevant percentage of glimepiride generics may offer reduced quality and performance when compared with the original drug.

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. METHODS: The PROactive study was a prospective, multicenter, double-blind, placebo-controlled trial of 5,238 patients with type 2 diabetes and macrovascular disease. Patients were randomized to either pioglitazone or placebo in addition to their other glucose-lowering and cardiovascular medication. Treatment of diabetes, dyslipidemia, and hypertension was encouraged according to the International Diabetes Federation guidelines. Patients were followed for a mean of 2.85 years. The primary end point was the time to first occurrence of macrovascular events or death. Of the total cohort, the subgroup of patients who had a previous MI (n = 2,445 [46.7%]; n = 1,230 in the pioglitazone group and n = 1,215 in the placebo group) was evaluated using prespecified and post-hoc analyses. RESULTS: Pioglitazone had a statistically significant beneficial effect on the prespecified end point of fatal and nonfatal MI (28% risk reduction [RR]; p = 0.045) and acute coronary syndrome (ACS) (37% RR; p = 0.035). There was a 19% RR in the cardiac composite end point of nonfatal MI (excluding silent MI), coronary revascularization, ACS, and cardiac death (p = 0.033). The difference in the primary end point defined in the main PROactive study did not reach significance in the MI population (12% RR; p = 0.135). The rates of heart failure requiring hospitalization were 7.5% (92 of 1,230) with pioglitazone and 5.2% (63 of 1,215) with placebo. Fatal heart failure rates were similar (1.4% [17 of the 92] with pioglitazone versus 0.9% [11 of the 63] with placebo). CONCLUSIONS: In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS. (PROspective pioglitAzone Clinical Trial In macroVascular Events; http://www.clinicaltrials.gov/ct/show/NCT00174993?order = 1; ISRCTN NCT00174993).

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. Real-time applications are based on an insulin standardised model. Clinical data were used to estimate model parameters. Root mean square error between simulated and real blood glucose profiles (G(rms)) was used to evaluate system efficacy. Results from parameter estimation and insulin standardisation showed a good capability of the model to identify individual characteristics. Simulation results with a G(rms) 1.30 mmol/l in the worst case testified the capacity of the model to accurately represent glucose-insulin relationship in type 1 diabetes allowing self tuning in real time.

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. FINDINGS: Current guidelines recommend glycated hemoglobin (HbA1c) target levels of approximately 6.0-7.5%. However, European and US data suggest that HbA1c targets are achieved by only approximately one-third of patients with type 2 diabetes. Progression from pre-diabetic impaired glucose tolerance to type 2 diabetes has recently become a target for early intervention with pharmacological agents. The aggressive treatment of dyslipidemia towards defined target levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol is recommended. The ADA and IDF recommend blood pressure targets of 130/80 mmHg in type 2 diabetes, and the use of aspirin for secondary cardiovascular disease prevention and primary prevention in patients at increased risk. Although inflammatory biomarkers, such as C-reactive protein, may predict type 2 diabetes risk, their role remains unclear. CONCLUSIONS: Concerted efforts are necessary to increase the proportion of patients achieving current treatment targets. Such measures must aim to educate patients and physicians, remove barriers due to health care organization and access, and improve the monitoring of cardiovascular disease risk indicators. The poly-pharmacy 'pill burden' may be alleviated through the use of drugs that are effective against multiple aspects of the metabolic syndrome, and by co-formulation of agents with established efficacy.

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. The questionnaire was administered to 400 specialists in laboratory medicine working in public or private laboratories nationwide participating in the "Italian External Evaluation of Quality in Laboratory Medicine" Study Group. RESULTS: The survey was completed in the period from June to September 2003. In the observation period, 241 questionnaires were returned by specialists working in laboratories scattered throughout 15 out of the 20 Italian regions. Only 50% of the laboratories performed the OGTT according to protocols defined in agreement with local reference diabetes centres. OGTT using 75 g of glucose in adults and 1.75 g/kg for children as recommended by WHO was performed by 87.1% of the laboratories. WHO indications to collect samples at baseline and at 120 min were followed by 33.2% of the centres. Higher variability was highlighted with respect to the methodology for GDM screening: 49.8% of the laboratories always adopted the two-step procedure consisting of a glucose challenge test (GCT) and subsequent OGTT in positive cases; 4.9% performed the 100-g OGTT with four blood samples; 1.6% the 75-g OGTT with two blood samples; and 2.7% the 75-g OGTT with four blood samples. More than 30% of the centres referred to different diagnostic schemes, 62% of which used individually chosen procedures amongst those reported above, 19% used only the GCT and no subsequent OGTT in positive cases, and 18.4% used a variety of completely different, arbitrarily chosen methods. Finally, only 25.6% of the laboratories referred to the WHO limits for interpretation of the results. CONCLUSIONS: For the Italian laboratories investigated, relevant variability was highlighted for performance of the OGTT in general and GDM screening in particular. A variable relationship between laboratories and diabetes centres was also detected, which might represent a relevant indicator for the need for rationalisation or standardisation of the method for performing an OGTT. These data highlight the need for greater collaboration between these different bodies. We suggest that other similar investigations should be carried out in other countries within the framework of the IFCC Global Campaign on Diabetes Mellitus.