Practical steps to improving the management of type 1 diabetes: recommendations from the Global Partnership for Effective Diabetes Management

The Diabetes Control and Complications Trial (DCCT) led to considerable improvements in the management of type 1 diabetes, with the wider adoption of intensive insulin therapy to reduce the risk of complications. However, a large gap between evidence and practice remains, as recently shown by the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, in which 30-year rates of microvascular complications in the ‘real world’ EDC patients were twice that of DCCT patients who received intensive insulin therapy. This gap may be attributed to the many challenges that patients and practitioners face in the day-to-day management of the disease. These barriers include reaching glycaemic goals, overcoming the reality and fear of hypoglycaemia, and appropriate insulin therapy and dose adjustment. As practitioners, the question remains: how do we help patients with type 1 diabetes manage glycaemia while overcoming barriers? In this article, the Global Partnership for Effective Diabetes Management provides practical recommendations to help improve the care of patients with type 1 diabetes

Panethnic Differences in Blood Pressure in Europe: A Systematic Review and Meta-Analysis

BACKGROUND: People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU. METHODS AND FINDINGS: We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence. CONCLUSIONS: 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The most appropriate therapeutic strategy for acute lower respiratory tract infections: a Delphi-based approach

Lower respiratory tract infections (LRTIs) cause high morbidity and mortality worldwide. Empiric therapy often base the choice of antibiotic treatment on antibacterial spectrum of the agent rather than on its pharmacological properties or the pathogen resistance profile. Inappropriate prescribing leads to therapeutic failure and antibiotic resistance, with increasing direct and indirect health costs. A consensus on appropriate prescribing in LRTI therapy was appraised by this Delphi exercise, based on a panel of 70 pulmonologists, coordinated by a Scientific Committee of nine experts in respiratory medical care. Full or very high consensus was reached on several issues, including the role of oral cephalosporins in first-line treatments of LRTIs and the appropriateness of cefditoren, with balanced spectrum and high intrinsic activity, in LRTI treatment. Evidence-based medicine approach and a comprehensive process of disease management, from diagnosis to therapy and follow-up, should guide antibiotic prescribing

Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction.

Aims/hypothesis Endothelium-derived factors are thought to be physiological modulators of large artery stiffness. The aim of the study was to investigate whether endothelial function could be a determinant of arterial stiffness in essential hypertensive patients, in relation with the concomitant presence of type 2 diabetes mellitus. Methods The study included 341 participants (84 hypertensive patients with and 175 without type 2 diabetes mellitus, 82 matched controls). Brachial artery endotheliumdependent flow-mediated dilation (FMD) was determined by high-resolution ultrasound and computerised edge detection system. Applanation tonometry was used to measure carotid-femoral pulse wave velocity (PWV). Results Hypertensive patients with diabetes had higher PWV (10.1±2.3 m/s vs 8.6±1.4 m/s, p<0.001) and lower FMD (3.51±2.07 vs 5.16±2.96%, p<0.001) than non-diabetic hypertensive patients, who showed impaired vascular function when compared with healthy participants (7.9±1.6 m/s and 6.68±3.67%). FMD was significantly and negatively correlated to PWV only in hypertensive diabetic patients (r0-0.456, p<0.001), but not in hypertensive normoglycaemic patients (r0-0.088, p00.248) or in healthy participants (r00.008, p00.946). Multivariate analysis demonstrated that, in the diabetic group, FMD remained an independent predictor of PWV after adjustment for confounders (r200.083, p00.003). Subgroup analysis performed in non-diabetic hypertensive patients revealed that neither obesity nor the metabolic syndrome affected the relationship between FMD and PWV. Conclusions/interpretation Endothelial dysfunction is a determinant of aortic stiffness in hypertensive diabetic patients but not in hypertensive patients without diabetes. These results suggest that type 2 diabetes mellitus on top of hypertension might worsen arterial compliance by endothelium-related mechanisms. Endothelium-derived factors are thought to be physiological modulators of large artery stiffness. The aim of the study was to investigate whether endothelial function could be a determinant of arterial stiffness in essential hypertensive patients, in relation with the concomitant presence of type 2 diabetes mellitus. METHODS: The study included 341 participants (84 hypertensive patients with and 175 without type 2 diabetes mellitus, 82 matched controls). Brachial artery endothelium-dependent flow-mediated dilation (FMD) was determined by high-resolution ultrasound and computerised edge detection system. Applanation tonometry was used to measure carotid-femoral pulse wave velocity (PWV). RESULTS: Hypertensive patients with diabetes had higher PWV (10.1 ± 2.3 m/s vs 8.6 ± 1.4 m/s, p < 0.001) and lower FMD (3.51 ± 2.07 vs 5.16 ± 2.96%, p < 0.001) than non-diabetic hypertensive patients, who showed impaired vascular function when compared with healthy participants (7.9 ± 1.6 m/s and 6.68 ± 3.67%). FMD was significantly and negatively correlated to PWV only in hypertensive diabetic patients (r = -0.456, p < 0.001), but not in hypertensive normoglycaemic patients (r = -0.088, p = 0.248) or in healthy participants (r = 0.008, p = 0.946). Multivariate analysis demonstrated that, in the diabetic group, FMD remained an independent predictor of PWV after adjustment for confounders (r (2) = 0.083, p = 0.003). Subgroup analysis performed in non-diabetic hypertensive patients revealed that neither obesity nor the metabolic syndrome affected the relationship between FMD and PWV. CONCLUSIONS/INTERPRETATION: Endothelial dysfunction is a determinant of aortic stiffness in hypertensive diabetic patients but not in hypertensive patients without diabetes. These results suggest that type 2 diabetes mellitus on top of hypertension might worsen arterial compliance by endothelium-related mechanisms

2009 SIPREC consensus document executive summary: Cardiovascular prevention in subjects with impaired fasting glucose or impaired glucose tolerance

Cardiovascular diseases still represent the leading cause of mortality and hospitalization, worldwide. As a consequence of the marked demographic changes observed in the general population, the improved survival rate after an acute cardiovascular event and the progressive rise of costs (mostly due to technological and pharmacological innovations), the estimated burden of cardiovascular diseases will be soon become insurmountable for national healthcare systems. In this view, an integrated approach aimed at improving strategies for cardiovascular disease prevention and, thus, limiting the negative outcomes, would probably be successful. Such an approach may not only achieve long-term benefits, but even significant advantages in the short to medium term, mostly in asymptomatic high-risk individuals. Indeed, this latter population of asymptomatic high-risk individuals would mostly benefit from extensive application and improvement of strategies for cardiovascular disease prevention with a favourable cost-benefit ratio.The Italian Society for Cardiovascular Disease Prevention Societ Italiana per la Prevenzione Cardiovascolare (SIPREC) has recognized this strategic aim, focusing a significant part of its institutional actions on the effort for providing educational supports and consensus documents, which represent an overview of the scientific knowledge and personal clinical expertise by national and international key opinion leaders. Expert committees periodically generate 'state-of-the-art' documents on specific scientific topics with relevant socioeconomic implications and large clinical impact. The present article is dedicated to healthcare professionals, is based on the available evidence, and provides information on diagnostic algorithms and therapeutic options on abnormal glucose regulation (or dysglycaemia).The relationship between abnormalities in glucose metabolism and cardiovascular complications represents an important and relatively early target for cardiovascular disease prevention. SIPREC identified, even in this clinical setting, a group of scientific experts in order to form a multidisciplinary 'task force'. This group has been asked to explain in a short, simple and effective fashion the epidemiological impact and the pathophysiological nature of the problem, its clinical features, potential diagnostic algorithms and therapeutic options, and its influence on the clinical practice of both specialist physicians and general practitioners.This work provides the background for discussing novel future strategies for cardiovascular prevention. It is also aimed at highlighting the importance of an emerging marker of cardiovascular risk, which is often not recognized and underestimated. © 2010 Adis Data Information BV. All rights reserved