The Contribution of Postprandial Glucose Levels to Hyperglycemia in Type 2 Diabetes Calculated from Continuous Glucose Monitoring Data: Real World Evidence from the DIALECT-2 Cohort.

Background/objectives: Traditional glycemic monitoring in type 2 diabetes is limited, whereas continuous glucose monitoring (CGM) offers better insights into glucose fluctuations. This study aimed to determine the correlations and relative contributions of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels to hyperglycemia.

Methods: We utilized CGM and recorded carbohydrate intake data from lifestyle diaries of 59 patients enrolled in the Diabetes and Lifestyle Cohort Twente (DIALECT-2).

Use of maximal dosage renin-angiotensin-aldosterone system inhibitors in a real life population of complicated type 2 diabetes - contraindications and opportunities.

Objective: Pharmacological inhibition of the renin-angiotensin-aldosterone-system (RAASi) is the cornerstone of hypertension treatment, renoprotection and secondary prevention of cardiovascular disease in patients with type 2 diabetes. Although there is a dose-dependent effect of RAASi with optimum protection when using maximal dose, little is known on actual use of maximal dosage RAASi in clinical practice. Here we investigate prevalence of maximal dosage RAASi, and contraindications for, optimizing RAASi dosage, in patients with complicated type 2 diabetes in a real-life clinical setting.

Low Urinary Potassium Excretion Is Associated with Higher Risk of All-Cause Mortality in Patients with Type 2 Diabetes: Results of the Dutch Diabetes and Lifestyle Cohort Twente (DIALECT).

Background: Low 24-h urinary potassium excretion, reflecting low potassium intake, is associated with premature mortality in the general population.

Objectives: To determine whether urinary potassium excretion is associated with all-cause mortality in patients with type 2 diabetes.

Methods: We performed a prospective cohort study in 654 patients with type 2 diabetes in the Diabetes and Lifestyle Cohort Twente (DIALECT).

Cadmium, active smoking and renal function deterioration in patients with type 2 diabetes.

Background: Cadmium is an established nephrotoxin, present in cigarette smoke. We investigated the hazards of cadmium concentration and smoking status on renal function deterioration. We furthermore discerned whether the association of cadmium concentration with renal function deterioration is attributable to smoking status.

Adherence to Statin Therapy and Attainment of LDL Cholesterol Targets in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT).

To assess adherence to statin therapy and its association with sociodemographic data, medical characteristics, LDLc levels, and LDLc target attainment in real-world T2D patients treated in secondary care. Cross-sectional analyses were performed on baseline data of 393 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT). The medication possession ratio (MPR), calculated with pharmacy dispensing data, was used to determine adherence to statins for an intended period of 24 months.

Personalized Nutrition in Patients with Type 2 Diabetes and Chronic Kidney Disease: The Two-Edged Sword of Dietary Protein Intake.

In type 2 diabetes (T2D), there is a general and strong focus on carbohydrate restriction. However, this may have unwarranted consequences for those with concomitant chronic kidney disease (CKD) since decreasing intake of carbohydrates implies a higher proportion of dietary protein, which is of critical debate in patients with CKD due to its ambiguous implications in maintaining either kidney function or nutritional status. We evaluated adherence to the protein recommendations, taking into account the nutritional status of patients with T2D with or without CKD.

Clinical and Dietary Determinants of Muscle Mass in Patients with Type 2 Diabetes: Data from the Diabetes and Lifestyle Cohort Twente.

Low muscle mass in patients with type 2 diabetes is associated with a progressively higher risk of morbidity and mortality. The aim of this study was to identify modifiable targets for intervention of muscle mass in type 2 diabetes. Cross-sectional analyses were performed in 375 patients of the Diabetes and Lifestyle Cohort Twente-1 study.

High-Normal Protein Intake Is Not Associated With Faster Renal Function Deterioration in Patients With Type 2 Diabetes: A Prospective Analysis in the DIALECT Cohort.

Objective: To study the prospective association between dietary protein intake and renal function deterioration in patients with type 2 diabetes (T2D).

Research Design And Methods: Prospective analyses were performed in data of 382 patients of the Diabetes and Lifestyle Cohort Twente (DIALECT) study. Dietary protein intake was determined by the Maroni equation from 24-h urinary urea excretion.

Biochemical Urine Testing of Medication Adherence and Its Association With Clinical Markers in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT).

Objective: To assess adherence to the three main drug classes in real-world patients with type 2 diabetes using biochemical urine testing, and to determine the association of nonadherence with baseline demographics, treatment targets, and complications.

Research Design And Methods: Analyses were performed of baseline data on 457 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT) study. Adherence to oral antidiabetics (OADs), antihypertensives, and statins was determined by analyzing baseline urine samples using liquid chromatography-tandem mass spectrometry.

Determinants of Increased Serum Calprotectin in Patients with Type 2 Diabetes Mellitus.

Circulating calprotectin is a potential biomarker for endovascular inflammation in type 2 diabetes mellitus (T2DM). We investigated the determinants of calprotectin and its relationship with the presence of cardiovascular disease (CVD) in 362 T2DM patients included in the Diabetes and Lifestyle Cohort Twente-1 (DIALECT-1) study. Lifestyle exposures, including nutrition, were determined by validated questionnaires.

Low Physical Activity in Patients with Complicated Type 2 Diabetes Mellitus Is Associated with Low Muscle Mass and Low Protein Intake.

Objective: In order to promote physical activity (PA) in patients with complicated type 2 diabetes, a better understanding of daily movement is required. We (1) objectively assessed PA in patients with type 2 diabetes, and (2) studied the association between muscle mass, dietary protein intake, and PA. Methods We performed cross-sectional analyses in all patients included in the Diabetes and Lifestyle Cohort Twente (DIALECT) between November 2016 and November 2018.

High Dietary Intake of Vegetable Protein Is Associated With Lower Prevalence of Renal Function Impairment: Results of the Dutch DIALECT-1 Cohort.

Introduction: Dietary protein intake may influence development of renal function impairment in diabetes mellitus type 2 (T2DM). We assessed the association between sources of protein and prevalence of renal function impairment.

Methods: Cross-sectional analyses were performed in baseline data of 420 patients of the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1) study.

Requirements of an Application to Monitor Diet, Physical Activity and Glucose Values in Patients with Type 2 Diabetes: The Diameter.

Adherence to a healthy diet and regular physical activity are two important factors in sufficient type 2 diabetes mellitus management. It is recognized that the traditional treatment of outpatients does not meet the requirements for sufficient lifestyle management. It is hypothesised that a personalized diabetes management mHealth application can help.

Proposal for a risk banding framework for inhaled low aspect ratio nanoparticles based on physicochemical properties.

We present a conceptual framework that can be used to assign risk bands to inhaled low aspect ratio nanoparticles starting from exposure bands assigned to a specific exposure situation. The framework mimics a basic physiological scheme that captures the essential mechanisms of fate and toxicity of inhaled nanoparticles and is composed of several models and rules that estimate the result of the following processes: the deposition of particles in the respiratory tract, their (de-)agglomeration, lung burden and clearance, their diffusion through the lung mucus layer, translocation and cellular uptake and local and systemic toxicity. Each model is based on a set of particle's physicochemical properties, including the size and size distribution(s), the zeta potential (or net charge at a specific pH), the surface hydrophobicity or hydrophilicity, the conduction band energy (for metals, metal oxides, quantum dots, etc.

Protein and lipid binding parameters in rainbow trout (Oncorhynchus mykiss) blood and liver fractions to extrapolate from an in vitro metabolic degradation assay to in vivo bioaccumulation potential of hydrophobic organic chemicals.

Binding of hydrophobic chemicals to colloids such as proteins or lipids is difficult to measure using classical microdialysis methods due to low aqueous concentrations, adsorption to dialysis membranes and test vessels, and slow kinetics of equilibration. Here, we employed a three-phase partitioning system where silicone (polydimethylsiloxane, PDMS) serves as a third phase to determine partitioning between water and colloids and acts at the same time as a dosing device for hydrophobic chemicals. The applicability of this method was demonstrated with bovine serum albumin (BSA).

Development of a partition-controlled dosing system for cell assays.

Hydrophobic and volatile chemicals have proven to be difficult to dose in cell assays. Cosolvents are often needed to dissolve these chemicals in cell culture medium. Moreover, the free concentration of these chemicals in culture medium may diminish over time due to metabolism, evaporation, and nonspecific binding to well plate surfaces and serum constituents.

CD27-CD70 interactions sensitise naive CD4+ T cells for IL-12-induced Th1 cell development.

Stimulation of CD27, a member of the tumour necrosis factor receptor family, by its ligand CD70 induces expansion of IFNgamma secreting CD4+ and CD8+ T cells in vivo. We here analysed the mechanisms through which CD27 mediates this effect. CD27 co-stimulation induced cell division but did not directly instruct naive CD4+ T cells to differentiate into IFNgamma-producing Th1 cells.

A randomised controlled trial of cardiac rehabilitation after revascularisation.

Background: It is unclear if psycho-education on top of physical training is of additional value regarding quality of life in revascularised patients.

Design: Prospective randomised study comparing two types of cardiac rehabilitation: exercise based versus a more comprehensive approach including psychological therapy.

Methods: One hundred and thirty-seven male patients who underwent an uncomplicated coronary revascularisation procedure and who were mentally in a good condition, were randomised to one of two types of cardiac rehabilitation: physical training plus information about their disease ('Fit' program) during 6 weeks or comprehensive cardiac rehabilitation which, on top of the Fit-program, included weekly psycho-education sessions and relaxation therapy ('Fit-Plus' program) for 8 weeks.

Immune activation modulates hematopoiesis through interactions between CD27 and CD70.

The differentiation of hematopoietic stem cells into mature blood cell lineages is tightly regulated. Here we report that CD27, which is expressed on stem and early progenitor cells in bone marrow, can be important in this process. Deletion of CD27 increased the myeloid colony-forming potential of stem and early progenitor cells and enhanced B lymphoid reconstitutive capacity in competitive transplantation experiments.

CD40 stimulation of B-cell chronic lymphocytic leukaemia cells enhances the anti-apoptotic profile, but also Bid expression and cells remain susceptible to autologous cytotoxic T-lymphocyte attack.

To enhance the poor antigen-presenting capacity of B-cell chronic lymphocytic leukaemia (B-CLL), CD40 triggering has been considered as an active immunotherapy. However, CD40 stimulation also has an anti-apoptotic effect and may further impair the dysregulated response of B-CLL to apoptotic stimuli. Therefore, we measured the expression of virtually all regulators of apoptosis before and after CD40 stimulation.

[Cardiac rehabilitation in patients with a congenital heart disease, an implantable cardioverter defibrillator or chronic heart failure].

Cardiac rehabilitation is no longer just used to treat patients after the manifestation of a coronary artery disease such as a myocardial infarct, after a PTCA or after a coronary bypass operation. Patients with a congenital heart disease, patients who have received an implantable cardioverter defibrillator (ICD) and patients with stable chronic heart failure are also suitable candidates for a multidisciplinary cardiac rehabilitation programme. The new Dutch guidelines for cardiac rehabilitation, published in 2004, can be helpful in identifying potential candidates for a programme.

Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation.

In vivo priming of antigen-specific CD8+ T cells results in their expansion and differentiation into effector T cells followed by contraction into a memory T cell population that can be maintained for life. Recent evidence suggests that after initial antigenic stimulation, the magnitude and kinetics of the CD8+ T cell response are programmed. However, it is unclear to what extent CD8+ T cell instruction in vivo is modulated by costimulatory signals.

Blockage of transcription as a trigger for p53 accumulation by 2-acetylaminofluorene DNA-adducts.

The hepatocarcinogen 2-acetylaminofluorene is one of the most studied experimental carcinogens. We have shown previously that normal rat hepatocytes accumulate the tumour suppressor p53 after exposure to this compound while preneoplastic rat hepatocytes do not. We suggested that the lack of p53 response may confer a growth advantage on preneoplastic hepatocytes and may be an important factor in hepatic tumor promotion by 2-acetylaminofluorene and other genotoxic compounds.