Search

Background The role of fibroblast growth factor 23 (FGF23) in the development of new‐onset heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) in the general population is unknown. Therefore, we set out to investigate associations of C‐terminal FGF23 with development of new‐onset HF and, more specifically, with HFrEF or HFpEF in a large, prospective, population‐based cohort. Methods and Results We studied 6830 participants (aged 53.8±12.1 years; 49.7% men; estimated glomerular filtration rate, 93.1±15.7 mL/min per 1.73 m 2 ) in the community‐based PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study who were free of HF at baseline. Cross‐sectional multivariable linear regression analysis showed that ferritin (standardized β, −0.24; P P Conclusions Higher FGF23 is independently associated with new‐onset HFrEF in analyses fully adjusted for cardiovascular risk factors and other potential confounders. The association between FGF23 and incident HFpEF lost statistical significance upon multivariable adjustment.

Background The cause of heart failure with preserved ejection fraction (HFpEF) is poorly understood, and specific therapies are lacking. Previous studies suggested that inflammation plays a role in the development of HFpEF. Herein, we aimed to investigate in community‐dwelling individuals whether a higher plasma interleukin 6 (IL‐6) level is associated with an increased risk of developing new‐onset heart failure (HF) over time, and specifically HFpEF. Methods and Results We performed a case‐cohort study based on the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study, a prospective general population‐based cohort study. We included 961 participants, comprising 200 participants who developed HF and a random group of 761 controls. HF with reduced ejection fraction or HFpEF was defined on the basis of the left ventricular ejection fraction of ≤40% or >40%, respectively. In Cox proportional hazard regression analyses, IL‐6 levels were statistically significantly associated with the development of HF (hazard ratio [HR], 1.28; 95% CI, 1.02–1.61; P =0.03) after adjustment for key risk factors. Specifically, IL‐6 levels were significantly associated with the development of HFpEF (HR, 1.59; 95% CI, 1.16–2.19; P =0.004), whereas the association with HF with reduced ejection fraction was nonsignificant (HR, 1.05; 95% CI, 0.75–1.47; P =0.77). In sensitivity analyses, defining HFpEF as left ventricular ejection fraction ≥50%, IL‐6 levels were also significantly associated with the development of HFpEF (HR, 1.47; 95% CI, 1.04–2.06; P =0.03) after adjustment for key risk factors. Conclusions IL‐6 is associated with new‐onset HFpEF in community‐dwelling individuals, independent of potential confounders. Our findings warrant further research to investigate whether IL‐6 might be a novel treatment target to prevent HFpEF.

Background Serum sulfhydryl groups (R-SH, free thiols) reliably reflect the systemic redox status in health and disease. As oxidation of R-SH occurs rapidly by reactive oxygen species (ROS), oxidative stress is accompanied by reduced levels of free thiols. Oxidative stress has been implicated in the pathophysiology of chronic kidney disease (CKD), in which redox imbalance may precede the onset of CKD. Therefore, we aimed to investigate associations between serum free thiols and the risk of incident CKD as defined by renal function decline and albuminuria in a population-based cohort study. Methods Subjects without CKD (n = 4,745) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, a prospective, population-based cohort study in the Netherlands, were included. Baseline protein-adjusted serum free thiols were studied for their associations with the development of CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) 30 mg/24-h, or both. Results Median level of protein-adjusted serum free thiols at baseline was 5.14 μmol/g of protein (interquartile range [IQR]: 4.50–5.75 μmol/g) and median eGFR was 96 mL/min/1.73 m2 [IQR: 85–106]. Protein-adjusted serum free thiols were significantly associated with incident CKD (hazard ratio [HR] per doubling 0.42 [95% confidence interval [CI]: 0.36–0.52, P 30 mg/24-h after full adjustment for confounding factors (HR per doubling 0.70 [95% CI: 0.51–0.96], P=0.028). Conclusion Higher levels of serum R-SH, reflecting less oxidative stress, are associated with a decreased risk of developing CKD in subjects from the general population. This association is primarily driven by incident CKD as defined by UAE., Graphical abstract Image 1, Highlights • Oxidative stress is implicated in the pathophysiology of chronic kidney disease (CKD). • Serum sulfhydryl groups (R-SH) reflect whole-body redox status in health and disease. • Serum R-SH associate with new-onset cardiovascular morbidity in many patient cohorts. • High serum R-SH are associated with a decreased risk of new-onset CKD in the general population. • Serum R-SH may potentially serve as screening tool for future CKD development.

This review provides an overview of the clinical value of the most relevant renal biomarkers, focusing on two main clinical conditions: acute kidney injury and chronic kidney disease. We categorize biomarkers according to their actionability, in terms of a documented response to treatment in relation to outcomes. Furthermore, we introduce a new category of renal biomarkers, metabolic biomarkers, and underscore their capacity to be highly actionable.

Sodium restriction may potentially reduce iodine intake. This study aimed to determine the effect of sodium restriction (dietary counseling) on 24-h urinary iodine excretion. Diuretics provide an alternative to sodium restriction and are frequently added to sodium restriction, so the effects of hydrochlorothiazide (50 mg daily) and combined therapy were also studied. We performed a post-hoc analysis of a Dutch multi-center, randomized cross-over trial in 45 patients with diabetic kidney disease with a mean age of 65 &plusmn, 9 years, mean eGFR of 65 &plusmn, 27 mL/min/1.73 m2, median albuminuria of 648 [230&ndash, 2008] mg/24 h and 84% were male. During regular sodium intake with placebo, mean 24 h urinary sodium and iodine excretion were 224 &plusmn, 76 mmol/24 h and 252 &plusmn, 94 ug/24 h, respectively (r = 0.52, p &lt, 0.001). Mean iodine excretion did not change significantly if sodium restriction and hydrochlorothiazide were applied separately, mean difference &minus, 8 ug/day (95% CI &minus, 38, 22, p = 0.6) and 14 ug/day (95% CI &minus, 24, 52, p = 0.5), respectively. Combined therapy induced a significant decrease in mean iodine excretion (&minus, 37 ug/day, 95% CI &minus, 67, &minus, 7, p = 0.02), yet this was not seen to a clinically meaningful level. The number of patients with an estimated intake below recommended daily allowances did not differ significantly between the four treatment periods (p = 0.3). These findings show that sodium restriction is not a risk factor for iodine deficiency.

BackgroundAlthough weight gain increases risk of type 2 diabetes, real-life data on the weight course in patients with established type 2 diabetes are scarce. We assessed weight course in a real-life diabetes secondary care setting and analyzed its association with patient characteristics, lifestyle habits and initiation of insulin, glucagon like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i).MethodsData on weight, insulin, GLP-1 RA and SGLT-2i use were collected retrospectively (12 years) and prospectively (8 years) from patients included in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1, n = 450, age 63 ± 9 years, 58% men, diabetes duration [7-18] years). Lifestyle habits were assessed using validated questionnaires. The association of clinical parameters with body mass index (BMI) course was determined using linear mixed models. Patients who underwent bariatric surgery (n = 19) had a distinct BMI course and were excluded from the study.ResultsBaseline BMI was 31.3 (0.3) and was higher in women, patients aged ConclusionsHigh BMI that real-life patients with type 2 diabetes gained earlier in life, remained stable in the following decades. Weight loss interventions should remain a priority, and GLP-1 RA might be considered to support weight loss.

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. Protein intake was assessed using a Food Frequency Questionnaire, modified for accurate assessment of protein intake, including types and sources of protein. Renal function impairment was defined as estimated glomerular filtration rate (eGFR), Graphical abstract

The majority of patients with type 2 diabetes do not reach target levels of glycated haemoglobin (HbA1c < 7%). We investigated the prevalence of HbA1c-target achievement and opportunities afforded by lifestyle and pharmacological treatment to increase target achievement. We performed cross-sectional analyses of baseline data from the Diabetes and Lifestyle Cohort Twente-1 (DIALECT-1). Patients were divided according to (1) HbA1c

Background/Objectives Lowering low-density lipoprotein cholesterol (LDLc) in type 2 diabetes mellitus is of paramount importance in preventing cardiovascular disease. However, treatment targets for LDLc are often not reached. We studied the prevalence of LDLc target achievement in a real-life population of type 2 diabetes mellitus patients in secondary care, and investigated whether in those not on target, there is room for intensifying pharmacological and lifestyle management according to current treatment guidelines. Subjects/Methods We performed a cross-sectional analysis in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1; n = 450, age 63 ± 9 years, 58% men, diabetes duration 11 (7–18) years). At baseline, we determined plasma LDLc concentration, pharmacological treatment (i.e., statin use), and lifestyle (physical activity and dietary intake). Patients were divided according to LDLc 2.5 mmol/l. Dietary intake was collected from a validated Food Frequency Questionnaire (177 items) and we determined guideline adherence for different food groups. Physical activity was assessed with the Short Questionnaire to ASsess Health enhancing behavior. Results LDLc data were available in 428 type 2 diabetes mellitus patients. LDLc ≤ 2.5 mmol/l was achieved in 317 patients (76%). In total, 76% of patients used statins, in those with LDLc > 2.5 mmol/l, this was 44%. Adherence to lifestyle guidelines was not different between the LDLc groups and was as follows: body mass index 6%, physical activity 59%, vegetables 7%, fruit 28%, legumes 59%, nuts 14%, dairy 19%, fish 36%, tea 8%, fats 66%, red meat 12%, processed meat 2%, alcohol 71%, sweetened beverages 34%, and sodium 12%. Conclusions In type 2 diabetes mellitus patients in secondary health care, the target LDLc is achieved by three quarters of patients. Increasing statin treatment could be a first step to improve LDLc. In addition, there are ample opportunities for lifestyle management through increasing adherence to lifestyle guidelines.

In type 2 diabetes mellitus (T2D), the handling of magnesium is disturbed. Magnesium deficiency may be associated with a higher risk of coronary heart disease (CHD). We investigated the associations between (1) dietary magnesium intake; (2) 24 h urinary magnesium excretion; and (3) plasma magnesium concentration with prevalent CHD in T2D patients. This cross-sectional analysis was performed on baseline data from the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1, n = 450, age 63 ± 9 years, 57% men, and diabetes duration of 11 (7-18) years). Prevalence ratios (95% CI) of CHD by sex-specific quartiles of magnesium indicators, as well as by magnesium intake per dietary source, were determined using multivariable Cox proportional hazard models. CHD was present in 100 (22%) subjects. Adjusted CHD prevalence ratios for the highest compared to the lowest quartiles were 0.40 (0.20, 0.79) for magnesium intake, 0.63 (0.32, 1.26) for 24 h urinary magnesium excretion, and 0.62 (0.32, 1.20) for plasma magnesium concentration. For every 10 mg increase of magnesium intake from vegetables, the prevalence of CHD was, statistically non-significantly, lower (0.75 (0.52, 1.08)). In this T2D cohort, higher magnesium intake, higher 24 h urinary magnesium excretion, and higher plasma magnesium concentration are associated with a lower prevalence of CHD.

Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system (RAAS) blockade efficacy in non-diabetic nephropathy. We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide, separately and in combination, added to RAAS blockade on residual albuminuria in patients with type 2 diabetic nephropathy.In this multicentre, double-blind, placebo-controlled, crossover randomised trial, we included patients with type 2 diabetic nephropathy. Main entry criteria were microalbuminaria or macroalbuminuria, and creatinine clearance of 30 mL/min or higher with less than 6 mL/min decline in the previous year. We tested the separate and combined effects of sodium restriction (dietary counselling in the outpatient setting) and hydrochlorothiazide (50 mg daily), added to standardised maximal angiotensin-converting enzyme (ACE) inhibition (lisinopril 40 mg daily), on albuminuria (primary endpoint). Patients were given hydrochlorothiazide (50 mg per day) or placebo during four treatment periods of 6 weeks. Both treatments were combined with regular sodium diet or sodium restriction (target sodium intake 50 mmol Na(+) per day). The 6-week treatment periods were done consecutively in a random order. Patients were randomised in blocks of two patients. The trial was analysed by intention to treat. The trial is registered with TrialRegister.nl, number 2366.Of 89 eligible patients, 45 were included in the study. Both sodium restriction and hydrochlorothiazide significantly reduced albuminuria, irrespective of treatment sequence. Residual geometric mean albuminuria with baseline treatment was 711 mg per day (95% CI 485-1043); it was significantly reduced by sodium restriction (393 mg per day [258-599], p=0·0002), by hydrochlorothiazide (434 mg per day [306-618], p=0·0003), and to the greatest extent by their combination (306 mg per day [203-461], p0·0001). Orthostatic complaints were present in two patients (4%) during baseline treatment, five (11%) during addition of sodium restriction, five (11%) during hydrochlorothiazide treatment, and 12 (27%) during combination treatment. No serious adverse events occurred.We conclude that sodium restriction is an effective non-pharmacological intervention to increase RAAS blockade efficacy in type 2 diabetic nephropathy.None.