Prediction of mortality and major cardiovascular complications in type 2 diabetes: External validation of UK Prospective Diabetes Study outcomes model version 2 in two European observational cohorts.

Aim: To externally validate the UK Prospective Diabetes Study Outcomes Model version 2 (UKPDS-OM2) by comparing the predicted and observed outcomes in two European population-based cohorts of people with type 2 diabetes.

Materials And Methods: We used data from the Casale Monferrato Survey (CMS; n = 1931) and a subgroup of the Hoorn Diabetes Care System (DCS) cohort (n = 5188). The following outcomes were analysed: all-cause mortality, myocardial infarction (MI), ischaemic heart disease (IHD), stroke, and congestive heart failure (CHF).

Peptides Derived From Insulin Granule Proteins Are Targeted by CD8 T Cells Across MHC Class I Restrictions in Humans and NOD Mice.

The antigenic peptides processed by β-cells and presented through surface HLA class I molecules are poorly characterized. Each HLA variant (e.g.

Dysfunctional eating in type 2 diabetes mellitus: A multicenter Italian study of socio-demographic and clinical associations.

Background And Aims: Dysfunctional eating might impact on the management and metabolic control of type 2 diabetes (T2DM), modifying adherence to healthy diet and food choices.

Methods And Results: In a multicenter study, we assessed the prevalence of dysfunctional eating in 895 adult outpatients with T2DM (51% males, median age 67, median BMI 30.3 kg/m).

Conventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors.

Although CD8 T-cell-mediated autoimmune β cell destruction occurs in type 1 diabetes (T1D), the target epitopes processed and presented by β cells are unknown. To identify them, we combined peptidomics and transcriptomics strategies. Inflammatory cytokines increased peptide presentation in vitro, paralleling upregulation of human leukocyte antigen (HLA) class I expression.

The role of cannabinoid signaling in acute and chronic kidney diseases.

The endogenous cannabinoids anandamide and 2-arachidonoylglycerol bind to the cannabinoid receptors of type 1 and 2. These receptors are also the binding sites for exogenous, both natural and synthetic, cannabinoids that are used for recreation purposes. Until recently, cannabinoids and cannabinoid receptors have attracted little interest among nephrologists; however, a full endocannabinoid system (ECS) is present in the kidney and it has recently emerged as an important player in the pathogenesis of diabetic nephropathy, drug nephrotoxicity, and progressive chronic kidney disease.

Heat Shock Proteins in Vascular Diabetic Complications: Review and Future Perspective.

Heat shock proteins (HSPs) are a large family of proteins highly conserved throughout evolution because of their unique cytoprotective properties. Besides assisting protein refolding and regulating proteostasis under stressful conditions, HSPs also play an important role in protecting cells from oxidative stress, inflammation, and apoptosis. Therefore, HSPs are crucial in counteracting the deleterious effects of hyperglycemia in target organs of diabetes vascular complications.

NTproBNP in insulin-resistance mediated conditions: overweight/obesity, metabolic syndrome and diabetes. The population-based Casale Monferrato Study.

Background And Aims: NTproBNP and BNP levels are reduced in obese subjects, but population-based data comparing the pattern of this relationship in the full spectrum of insulin-resistance mediated conditions, overweight/obesity, metabolic syndrome and diabetes, are limited.

Methods: The study-base were 3244 individuals aged 45-74 years, none of whom had heart failure, 1880 without diabetes and 1364 with diabetes, identified as part of two surveys of the population-based Casale Monferrato Study. All measurements were centralized.

Short term variation in NTproBNP after lifestyle intervention in severe obesity.

Aim: Natriuretic peptides are not only involved in cardiovascular adaption to various conditions, but also in metabolic diseases. We performed this study to assess the effect of a very short time of lifestyle inpatient intervention on NTproBNP values in normotensive subjects with severe obesity and normal cardiac function.

Methods: We recruited 14 consecutive obese normotensive subjects with normal cardiac function who were aged 30 years and more and were referred to inpatient rehabilitation in an academic clinic over a two months period.

Incidence of prolonged QTc and severe hypoglycemia in type 1 diabetes: the EURODIAB Prospective Complications Study.

Aims: To assess the independent role of severe hypoglycemia on 7-year cumulative incidence of prolonged QTc in a large cohort of patients with type 1 diabetes.

Methods: People with type 1 diabetes recruited by the EURODIAB Prospective Complications Study who had normal QTc were examined at baseline and after 7 years with standardized methods (n = 1415; mean age ± SD 32.1 ± 9.

Dual therapy targeting the endocannabinoid system prevents experimental diabetic nephropathy.

Background: The endocannabinoid system has been implicated in the pathogenesis of diabetic nephropathy (DN). We investigated the effect of combined therapy with AM6545, a 'peripherally' restricted cannabinoid receptor type 1 (CB1R) neutral antagonist, and AM1241, a cannabinoid receptor type 2 (CB2R) agonist, in experimental DN.

Methods: Renal function and structure, podocyte proteins and markers of both fibrosis and inflammation were studied in streptozotocin-induced diabetic mice treated for 14 weeks with vehicle, AM6545, AM1241 and AM6545-AM1241.

MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study.

Aims: Increasing evidence suggests a potential role of circulating miRNAs as clinical biomarkers, and loss of miRNA-126 has been proposed as a predictor of type 2 diabetes onset. However, a systematic analysis of circulating miRNAs in type 1 diabetic patients with micro-/macrovascular complications has not yet been performed.

Methods: A cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 455 type 1 diabetic patients was performed.

Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island.

Background: Type 1 diabetes incidence presents a decreasing gradient in Europe from the Nordic countries to the Mediterranean ones. Exception to this gradient is represented by Sardinia, the second largest Mediterranean island whose population shows the highest incidence in Europe, after Finland. The genetic features of this population have created a fertile ground for the epidemic of the disease, however, as well as being strikingly high, the incidence rate has suddenly presented a continuous increase from the '50s, not explainable by accumulation of new genetic variants.

Vitamin D levels at birth and risk of type 1 diabetes in childhood: a case-control study.

Aims: To assess whether vitamin D levels at birth were associated with risk of having type 1 diabetes up to 10 years of age and the potential modifier effect of ethnic group.

Methods: The Piedmont Diabetes Registry and the Newborn Screening Regional data were linked to identify cases (n = 67 incident children aged ≤10 years at diabetes onset, 2002-2012) and up to five controls (n = 236) matched for birthday and ethnic group. Cards with neonatal blood spot were used and 25-hydroxyvitamin D(3) assessed with tandem mass spectroscopy.

Investigating obesity among professional drivers: the high risk professional driver study.

Objective: The aim of this study is to detect the main individual and transportation factors associated with obesity and its prevalence among Italian professional drivers (PDs).

Methods: We performed a cross-sectional questionnaire survey. Data from PDs (n = 497) were used for analyses.

NT-proBNP linking low-moderately impaired renal function and cardiovascular mortality in diabetic patients: the population-based Casale Monferrato Study.

Background: Few data are available to assess whether a low-moderate reduction in estimated glomerular filtration rates (eGFR) has a role per se on cardiovascular (CV) mortality or other biomarkers such as NT-proBNP allow to explain such association.

Methods And Findings: In a prospective study including 1,645 type 2 diabetic subjects of the population-based Casale Monferrato Study, who had no clinical evidence of heart failure and eGFR >45 ml/min/1.73 m2, we examined 6 years CV mortality.

Levels of N-terminal pro brain natriuretic peptide are enhanced in people with the uncomplicated metabolic syndrome: a case-cohort analysis of the population-based Casale Monferrato study.

Background: Both metabolic syndrome (MetS) and N-amino terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) confer increased risk of cardiovascular diseases (CVD). We assessed if NT-proBNP levels were greater in people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD) nor diabetes, as compared with subjects who met none of the defining criteria of the MetS.

Methods: A case-cohort study from the non-diabetic population-based Casale Monferrato study was performed, after exclusion of all subjects with established CVD, CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.

Natriuretic peptides, heart, and adipose tissue: new findings and future developments for diabetes research.

Natriuretic peptides (NPs) play a key role in cardiovascular homeostasis, counteracting the deleterious effects of volume and pressure overload and activating antibrotic and antihypertrophic pathways in the heart. N-terminal B-type NP (NT-proBNP) also is a promising biomarker of global cardiovascular risk in the general population, and there is increasing interest on its potential use in diabetic patients for screening of silent cardiovascular abnormalities, cardiovascular risk stratification, and guided intervention. Recently, both atrial NP (ANP) and B-type NP (BNP) have emerged as key mediators in the control of metabolic processes including the heart in the network of organs that regulate energy usage and metabolism.

Inflammation in diabetic nephropathy: moving toward clinical biomarkers and targets for treatment.

Diabetic nephropathy (DN) is a leading cause of end stage renal failure and there is an urgent need to identify new clinical biomarkers and targets for treatment to effectively prevent and slow the progression of the complication. Many lines of evidence show that inflammation is a cardinal pathogenetic mechanism in DN. Studies in animal models of experimental diabetes have demonstrated that there is a low-grade inflammation in the diabetic kidney.

Deficiency of cannabinoid receptor of type 2 worsens renal functional and structural abnormalities in streptozotocin-induced diabetic mice.

A functionally active endocannabinoid system is present within the kidney. The cannabinoid receptor type 2 (CB2) is expressed by both inflammatory cells and podocytes, and its activation has beneficial effects in experimental diabetic nephropathy. To further explore the role of CB2 in diabetic nephropathy, we studied renal functional and structural abnormalities in streptozotocin-induced diabetic CB2 knockout mice.

The effect of age and NT-proBNP on the association of central obesity with 6-years cardiovascular mortality of middle-aged and elderly diabetic people: the population-based Casale Monferrato study.

Background: Among people with type 2 diabetes the relationship between central obesity and cardiovascular mortality has not been definitely assessed. Moreover, NT-proBNP is negatively associated with central obesity, but no study has examined their combined effect on survival. We have examined these issues in a well-characterized population-based cohort.

Hospital admissions for hypertensive crisis in the emergency departments: a large multicenter Italian study.

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure ≥220 mmHg and/or diastolic blood pressure ≥120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively.