Contextualising evidence based medicine in determining the key root for translational effectiveness for chronic disease self-management and heart failure.

BACKGROUND: Congestive heart failure (CHF) management has proven devastating on morbidity, mortality, quality of life and also costly to health systems. Therapeutics for CHF have advanced and benefited greatly due to large multicentre randomised controlled trials and the evidence obtained from them. Management for chronic diseases and nonpharmaceutical therapies such as chronic disease self-management has lagged, and for CHF the evidence base has even been questioned. METHODS: Perspective and non systematic mini review. CONCLUSIONS: Advancing translational research standards is important to achieve optimal cost effectiveness. Importantly is understanding evidence generation in medicine, identifying the primary roots for management and its translation.

Vitamin D supplementation increases adipokine concentrations in overweight or obese adults.

PURPOSE: Vitamin D regulates adipokine production in vitro; however, clinical trials have been inconclusive. We conducted secondary analyses of a randomized controlled trial to examine whether vitamin D supplementation improves adipokine concentrations in overweight/obese and vitamin D-deficient adults. METHODS: Sixty-five individuals with a BMI ≥ 25 kg/m2 and 25-hydroxyvitamin D (25(OH)D) ≤ 50 nmol/L were randomized to oral cholecalciferol (100,000 IU single bolus followed by 4,000 IU daily) or matching placebo for 16 weeks. We measured BMI, waist-to-hip ratio, % body fat (dual X-ray absorptiometry), serum 25(OH)D (chemiluminescent immunoassay) and total adiponectin, leptin, resistin, and adipsin concentrations (multiplex assay; flow cytometry). Sun exposure, physical activity, and diet were assessed using questionnaires. RESULTS: Fifty-four participants completed the study (35M/19F; mean age = 31.9 ± 8.5 years; BMI = 30.9 ± 4.4 kg/m2). After 16 weeks, vitamin D supplementation increased 25(OH)D concentrations compared with placebo (57.0 ± 21.3 versus 1.9 ± 15.1 nmol/L, p < 0.001). There were no differences between groups for changes in adiponectin, leptin, resistin, or adipsin in unadjusted analyses (all p > 0.05). After adjustment for baseline values, season, sun exposure, and dietary vitamin D intake, there was a greater increase in adiponectin (ß[95%CI] = 13.7[2.0, 25.5], p = 0.02) and leptin (ß[95%CI] = 22.3[3.8, 40.9], p = 0.02) in the vitamin D group compared with placebo. Results remained significant after additional adjustment for age, sex, and % body fat (p < 0.02). CONCLUSIONS: Vitamin D may increase adiponectin and leptin concentrations in overweight/obese and vitamin D-deficient adults. Further studies are needed to clarify the molecular interactions between vitamin D and adipokines and the clinical implications of these interactions in the context of obesity. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT02112721.

Carnosine supplementation reduces plasma soluble transferrin receptor in healthy overweight or obese individuals: a pilot randomised trial.

Abnormalities of iron homeostasis have been linked to insulin resistance, type 2 diabetes and cardiovascular disease. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to decrease serum iron and improve glucose metabolism in diabetic rodents. We have previously demonstrated that carnosine supplementation prevented worsening of glucose metabolism in healthy overweight and obese middle-aged adults. Yet, the impact of carnosine on markers of iron metabolism in humans has not been investigated. We aimed to determine whether carnosine supplementation has an effect on iron parameters in overweight and obese, otherwise healthy adults. We included 26 participants, who were randomly allocated to receive 1 g carnosine (n = 14) or identical placebo (n = 12) twice daily for 12 weeks. Iron parameters including iron, ferritin, transferrin, soluble transferrin receptor, total iron binding capacity and iron saturation were measured in serum or plasma by standard commercial assays. Carnosine supplementation decreased plasma soluble transferrin receptor compared to placebo (mean change difference ± standard error: - 0.07 ± 0.03 mg/l, p = 0.04). None of the other iron parameters were different between carnosine and placebo groups. At follow-up, soluble transferrin receptor was associated inversely with urinary carnosine concentrations and positively with serum carnosinase-1 activity (both p < 0.02). Our findings suggest that carnosine may modulate iron metabolism in high-risk groups which could ameliorate insulin resistance and prevent type 2 diabetes. Larger human clinical trials are required to confirm our results.

Disparity in the micronutrient content of diets high or low in advanced glycation end products (AGEs) does not explain changes in insulin sensitivity.

We have previously shown that an isoenergetic low advanced glycation end products (AGEs) diet matched for macronutrient content improved insulin sensitivity compared to high AGE diet. Here, we evaluated the differences in micronutrient intake of these two dietary patterns and if they could explain differences in insulin sensitivity. Participants consumed the intervention diets each for 2 weeks with 4 weeks of habitual dietary intake (washout) in-between. Dietary analysis revealed that the high AGE diet contained greater levels of retinol equivalents (RE) (478.9 + 151.3 µg/day versus 329.0 + 170.0 µg/day; p < .006), vitamin A (806.3 + 223.5 (µg RE)/day versus 649.1 + 235.8 (µg RE)/day; p < .05) and thiamine (2.3 + 0.6 mg/day versus 1.6 + 0.4 mg/day; p = .014) compared to the low AGE diet. The changes in polyunsaturated fat, retinol, vitamin A and thiamine did not correlate with changes in insulin sensitivity (all p > .1) therefore are unlikely to explain observed changes in insulin sensitivity. (clinicaltrials.gov:NCT00422253).

Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects.

It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = -0.31; p < 0.05). In addition, fasting (r = -0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure.

BACKGROUND: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals. METHODS: We measured body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carboxymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC). RESULTS: Plasma CML concentrations were related to diastolic blood pressure (r=-0.51, p<0.01) independently of age, sex, BMI and WHR (p<0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r=0.47, p<0.01) before and after adjustment for age, sex, BMI and WHR (p<0.05). Plasma CML concentrations were related to the pulse pressure before (r=0.42; p<0.05) and after adjustment for age, sex, BMI and waist (p<0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p=ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p=ns). CONCLUSIONS: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.

Malthusian Trajectory for Heart Failure and Novel Translational Ambulatory Technologies.

INTRODUCTION: It has been estimated that congestive heart failure (CHF) will reach epidemic proportions and contribute to large unsustainable impacts on health budgets for any cardiovascular condition. Against other major trends in cardiovascular outcomes, readmission and disease burden continue to rise as the demographics shift. METHODS: The rise in heart failure with preserved ejection fraction (HFpEF) among elderly women will present new challenges. Gold standard care delivers sustainable and cost-effective health improvements using organised care programs. When coordinated with large hospitals, this can be replicated universally. RESULTS: A gradient of outcomes and ambulatory care needs to be shifted from established institutions and shared with clients and community health services, being a sizeable proportion of CHF care. CONCLUSION: In this review, we explore health technologies as an emerging opportunity to address gaps in CHF management.

The Wider Considerations in Closing Chronic Disease Gaps - Focus on Heart Failure and Implementation.

BACKGROUND: Heart failure (HF) is predominately a chronic disease. There are overlaps in HF and chronic disease research and care. Chronic disease and HF research are conducted with multiple goals. The overarching goal is "optimized patient outcomes at maximum costeffectiveness". However, observations on patients can come with many variables; thus, we see differences in clinical translation. This document discusses an argument for three important gaps common to HF and chronic disease, i.e., screening, self-management, and patient-reported outcomes (PRO), and provides a glance of how it could fit into the evidence tree. Pertinent arguments for a framework for health services and models of care are provided as a prelude to future consensus. METHODOLOGY: 1) A preliminary literature review to identify a taxonomy for cardiovascular research, and 2) a review of the published literature describing the translation of research studies into clinical practice for cardiovascular disorders. A spectrum from observational to large randomized controlled trials to post-marketing studies were identified. DISCUSSION: A brief discussion on traditional research and differences focusing on screening, mixed methods research concepts, and chronic diseases models of care. Six steps to facilitate this: 1) Research design; 2) Research application (translation) i. routine ii. challenges; 3. Transforming research to translational level; 4. Funding and infrastructure; 5. Clinical Centres of Research Excellence (CCRE) and collaboration; 6. Governance and cost-effectiveness. CONCLUSION: Implementation research that aims to link research findings to improved patient outcomes in an efficient and effective way is a neglected area. Skills required to perform implementation research are complex. Ways to maximize translational impacts for chronic disease research to clinical practice are described in a HF context.

Chronic disease IMPACT (chronic disease early detection and improved management in primary care project): An Australian stepped wedge cluster randomised trial.

Background: Interrelated chronic vascular diseases (chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease (CVD)) are common with high morbidity and mortality. This study aimed to assess if an electronic-technology-based quality improvement intervention in primary care could improve detection and management of people with and at risk of these diseases. Methods: Stepped-wedge trial with practices randomised to commence intervention in one of five 16-week periods. Intervention included (1) electronic-technology tool extracting data from general practice electronic medical records and generating graphs and lists for audit; (2) education regarding chronic disease and the electronic-technology tool; (3) assistance with quality improvement audit plan development, benchmarking, monitoring and support. De-identified data analysis using R 3.5.1 conducted using Bayesian generalised linear mixed model with practice and time-specific random intercepts. Results: At baseline, eight included practices had 37,946 active patients (attending practice ≥3 times within 2 years) aged ≥18 years. Intervention was associated with increased OR (95% CI) for: kidney health checks (estimated glomerular filtration rate, urine albumin:creatinine ratio (uACR) and blood pressure) in those at risk 1.34 (1.26-1.42); coded diagnosis of CKD 1.18 (1.09-1.27); T2D diagnostic testing (fasting glucose or HbA1c) in those at risk 1.15 (1.08-1.23); uACR in patients with T2D 1.78 (1.56-2.05). Documented eye checks within recommended frequency in patients with T2D decreased 0.85 (0.77-0.96). There were no significant changes in other assessed variables. Conclusions: This electronic-technology-based intervention in primary care has potential to help translate guidelines into practice but requires further refining to achieve widespread improvements across the interrelated chronic vascular diseases.

Perspective on 'Phase V' or Logistics and Regression as Logical Progression for Community Heart Failure Triage.

Congestive Heart Filur is an epidemic and its trajectory apppears to be escaling. Undoubtly tremendous gains have seen improvement in life expectancy and quality of life, however, hospital readmissions, resource utilization and health system cost continue to create challenges. In this short perspective, we raise the prospect of extending the research phases the community and real world setting. Logistic have supported service supply chains during the COVID-19 pandemic and there are lesson here to be learned.

Using electronic medical record data to assess chronic kidney disease, type 2 diabetes and cardiovascular disease testing, recognition and management as documented in Australian general practice: a cross-sectional analysis.

OBJECTIVES: To evaluate the capacity of general practice (GP) electronic medical record (EMR) data to assess risk factor detection, disease diagnostic testing, diagnosis, monitoring and pharmacotherapy for the interrelated chronic vascular diseases-chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease. DESIGN: Cross-sectional analysis of data extracted on a single date for each practice between 12 April 2017 and 18 April 2017 incorporating data from any time on or before data extraction, using baseline data from the Chronic Disease early detection and Improved Management in PrimAry Care ProjecT. Deidentified data were extracted from GP EMRs using the Pen Computer Systems Clinical Audit Tool and descriptive statistics used to describe the study population. SETTING: Eight GPs in Victoria, Australia. PARTICIPANTS: Patients were ≥18 years and attended GP ≥3 times within 24 months. 37 946 patients were included. RESULTS: Risk factor and disease testing/monitoring/treatment were assessed as per Australian guidelines (or US guidelines if none available), with guidelines simplified due to limitations in data availability where required. Risk factor assessment in those requiring it: 30% of patients had body mass index and 46% blood pressure within guideline recommended timeframes. Diagnostic testing in at-risk population: 17% had diagnostic testing as per recommendations for CKD and 37% for T2D. Possible undiagnosed disease: Pathology tests indicating possible disease with no diagnosis already coded were present in 6.7% for CKD, 1.6% for T2D and 0.33% familial hypercholesterolaemia. Overall prevalence: Coded diagnoses were recorded in 3.8% for CKD, 6.6% for T2D, 4.2% for ischaemic heart disease, 1% for heart failure, 1.7% for ischaemic stroke, 0.46% for peripheral vascular disease, 0.06% for familial hypercholesterolaemia and 2% for atrial fibrillation. Pharmaceutical prescriptions: the proportion of patients prescribed guideline-recommended medications ranged from 44% (beta blockers for patients with ischaemic heart disease) to 78% (antiplatelets or anticoagulants for patients with ischaemic stroke). CONCLUSIONS: Using GP EMR data, this study identified recorded diagnoses of chronic vascular diseases generally similar to, or higher than, reported national prevalence. It suggested low levels of extractable documented risk factor assessments, diagnostic testing in those at risk and prescription of guideline-recommended pharmacotherapy for some conditions. These baseline data highlight the utility of GP EMR data for potential use in epidemiological studies and by individual practices to guide targeted quality improvement. It also highlighted some of the challenges of using GP EMR data.

Targeted reduction of advanced glycation improves renal function in obesity.

Obesity is highly prevalent in Western populations and is considered a risk factor for the development of renal impairment. Interventions that reduce the tissue burden of advanced glycation end-products (AGEs) have shown promise in stemming the progression of chronic disease. Here we tested if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction. Overweight and obese individuals (body mass index (BMI) 26-39 kg/m(2)) were recruited to a randomized, crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet. Renal function and an inflammatory profile (monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF)) were improved following the low-AGE diet. Mechanisms of advanced glycation-related renal damage were investigated in a mouse model of obesity using the AGE-lowering pharmaceutical, alagebrium, and mice in which the receptor for AGE (RAGE) was deleted. Obesity, resulting from a diet high in both fat and AGE, caused renal impairment; however, treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion, creatinine clearance, the inflammatory profile, and renal oxidative stress. Alagebrium treatment, however, resulted in decreased weight gain and improved glycemic control compared with wild-type mice on a high-fat Western diet. Thus, targeted reduction of the advanced glycation pathway improved renal function in obesity.

Author Correction: Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Vitamin D supplementation improves waist-to-hip ratio and fasting blood glucose in vitamin D deficient, overweight or obese Asians: A pilot secondary analysis of a randomised controlled trial.

Recent trials do not support a role for vitamin D supplementation in prevention or treatment of type 2 diabetes mellitus, although effects may differ in Asian populations. In this pilot secondary analysis of a placebo-controlled randomised trial of overweight or obese individuals with low 25-hydroxyvitamin D (25(OH)D < 50 nmol/L), we examined whether vitamin D supplementation improved insulin sensitivity or body composition in participants of Asian ethnicity. Amongst 65 trial participants, 33 reported being of Asian descent (mean ± SD age 30 ± 7 years; 67% male). Participants were block randomised to receive vitamin D (n = 14; initial bolus dose of 2500 µg cholecalciferol followed by 100 µg cholecalciferol/d) or placebo (n = 19; identical capsules) for 16 weeks. Primary outcome was change in insulin sensitivity (M-value) assessed by hyperinsulinemic-euglycemic clamp. Secondary outcomes were changes in 25(OH)D (chemiluminescent immunoassay), fasting blood glucose (YSI Stat 2300), and body composition including waist-hip ratio and total body fat percentage (dual-energy X-ray absorptiometry). Questionnaires assessed sun-exposure habits, physical activity, and diet. After the 16-week intervention, 25(OH)D concentrations increased significantly in the vitamin D group with no change in placebo (61.4 ± 21.1 vs -0.4 ± 12.7 nmol/L; P < 0.01). Vitamin D group participants demonstrated significant improvements in waist-hip ratio (-0.02 ± 0.03 vs 0.00 ± 0.02; P < 0.01) and fasting blood glucose (-0.1 ± 0.2 vs 0.2 ± 04 mmol/L; P < 0.04) compared with the placebo group, but changes in insulin sensitivity and other body composition measures did not differ significantly between groups (all P > 0.05). In conclusion, vitamin D supplementation improved waist-hip ratio and fasting blood glucose in overweight and obese Asian-Australians with low vitamin D concentrations. Further research is required to determine whether vitamin D supplementation is potentially more effective in specific ethnic groups.

Vitamin D supplementation may improve back pain disability in vitamin D deficient and overweight or obese adults.

Back pain is currently the greatest cause of disability worldwide, and there are very limited therapeutic options available. Vitamin D deficiency and obesity are both risk factors for back pain. The few randomised controlled trials examining the effects of vitamin D supplementation on back pain have methodological limitations and largely include non-vitamin D deficient participants. Thus, the aim of this study was to determine whether vitamin D supplementation improves back pain symptoms in vitamin D deficient and overweight or obese, otherwise healthy adults. Sixty-five overweight or obese adults (BMI ≥ 25 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] concentrations ≤50 nmol/L) were randomised to a bolus oral dose of 100,000 IU followed by 4000 IU cholecalciferol/day or matching placebo for 16 weeks. We measured 25(OH)D concentrations (chemiluminescent immunoassays) and self-reported back pain (Chronic Pain Grade Questionnaire) before and after the intervention. Lifestyle habits including sun exposure, physical activity, and diet were collected using questionnaires. Fifty-four participants completed the study, of which 49 had complete data for back pain and were included in the present analyses (31 M/18 F; mean ± SD age: 31.8 ± 8.9 years; BMI: 31.1 ± 4.5 kg/m2). After the 16-week intervention, 25(OH)D levels increased significantly with vitamin D supplementation compared with placebo (55.7 ± 20.9 versus 3.9 ± 14.4 nmol/L, respectively, p < 0.001). There were no significant differences between vitamin D and placebo groups in change in back pain intensity or disability scores (all p > 0.05). However, in those with 25(OH)D concentrations <30 nmol/L at baseline (n = 20), there was a significantly greater reduction in back pain disability scores in the vitamin D group compared with placebo, after adjusting for important covariates known to affect vitamin D status and/or back pain (b [95%CI] = -11.6 [-22.4, -0.8], p = 0.04). Our findings suggest that vitamin D supplementation in overweight or obese and markedly vitamin D deficient adults (25(OH)D <30 nmol/L) may improve back pain disability. Although treating severe vitamin D deficiency is recommended for optimising bone health, this study suggests it may also improve back pain. Hence, testing for vitamin D deficiency in those with back pain who are overweight or obese may be warranted.

Vitamin D and symptoms of depression in overweight or obese adults: A cross-sectional study and randomized placebo-controlled trial.

Recent evidence suggests that vitamin D deficiency may contribute to increased risk of depression. However, previous studies are limited by variability in participant characteristics including vitamin D deficiency status and presence of existing diseases, use of low doses of vitamin D supplementation for short durations, and use of co-interventions or psychotropic drugs. We examined whether 25-hydroxyvitamin D (25(OH)D) concentrations were associated with symptoms of depression, as well as whether vitamin D supplementation reduced symptoms of depression in overweight or obese and vitamin D-deficient, but otherwise healthy adults. Cross-sectional analyses were performed on baseline data from 63 (39M/24F) overweight or obese (body mass index (BMI) ≥25kg/m2) and vitamin D-deficient (25(OH)D ≤50 nmol/l) adults (mean age=31.3±8.5), without clinical depression. Participants were randomized to either a bolus oral dose of 100,000 IU followed by 4000 IU daily of cholecalciferol, or matching placebo for 16 weeks. Interventional analyses were performed on data from 48 participants (30M/18F) who completed the trial. We measured serum 25(OH)D concentrations; anthropometry: BMI, waist-to-hip ratio (WHR), % body fat (dual X-ray absorptiometry); and depressive symptoms using the Beck Depression Inventory (BDI) before and after intervention. Data on dietary vitamin D intake (3-day food record), physical activity (international physical activity questionnaire), and sun exposure habits were collected using questionnaires. At baseline, mean 25(OH)D concentration was 32.9±11.3 nmol/l and total BDI score was 6.6±6.3 (range=0-33). There were no associations between 25(OH)D concentrations and total BDI scores or BDI subscales (all p>0.1). After the 16-week intervention, 25(OH)D concentrations increased in the vitamin D group compared to placebo (56.0±20.8 versus 2.7±13.9 nmol/L, respectively; p <0.0001). Change in total BDI scores did not differ between vitamin D and placebo groups (-2.0±4.5 versus -1.5±2.9, respectively; p=0.7). There were no differences in BDI subscales between groups (both p>0.1). Results remained non-significant after adjusting for multiple covariates including sun exposure, physical activity, and dietary vitamin D intake (all p>0.1). Our findings suggest that vitamin D deficiency may not be related to increased risk of depression in individuals without clinically significant depression and that the use of vitamin D supplementation may not be warranted for reducing depressive symptoms in this population. Further large-scale studies are needed to establish whether vitamin D supplementation may be beneficial for improving depressive symptoms in other population groups, including in those with existing depressive or psychiatric disorders.

Serum 25-hydroxyvitamin D concentrations are associated with nuclear factor kappa-B activity but not with inflammatory markers in healthy normoglycemic adults.

Vitamin D has been reported to have anti-inflammatory properties in in vitro and animal studies, which are thought to occur via inhibition of the nuclear factor kappa-B (NFκB) pathway. However, the association between vitamin D and in vivo NFκB activity in humans has not previously been reported. The aim of the present study was to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and NFκB activity in peripheral blood mononuclear cells (PBMCs) as well as plasma inflammatory markers in healthy individuals. We hypothesized that 25(OH)D concentrations would be negatively associated with NFκB activity and pro-inflammatory markers downstream of NFκB, and positively associated with anti-inflammatory markers. We measured circulating 25(OH)D (chemiluminescent immunoassay); anthropometry: body mass index (BMI), waist-to-hip ratio (WHR), and % body fat (dual X-ray absorptiometry); plasma pro- and anti-inflammatory markers: high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and IL-10 (ELISA); and NFκB activity in PBMCs (DNA-binding assay). Forty-nine participants were included in the study (21M/28F; age=31.6±10.2years (mean±SD); BMI=28.4±4.6kg/m2; % body fat=30.2±9.3%). Mean 25(OH)D concentration was 48.2±24.5 nmol/l. There were no differences in 25(OH)D concentrations between genders and no association between 25(OH)D concentrations and age, BMI, or % body fat (all p>0.1). Serum 25(OH)D concentrations were positively associated with NFκB activity in PBMCs (r=0.48, p=0.0008) but not with any of the pro- or anti-inflammatory markers measured (all p>0.1). After adjusting for age, sex, and % body fat, 25(OH)D concentrations remained positively associated with NFκB activity in PBMCs (ß=0.55, p<0.0001). Although in-vitro studies suggest that vitamin D inhibits NFκB activity, our novel cross-sectional data from a cohort of healthy individuals suggest that vitamin D may regulate rather than inhibit the NFκB pathway. Large-scale intervention and mechanistic studies are needed to further investigate the effects of vitamin D on NFκB activity in vivo in humans.

Erratum: Higher glomerular filtration rate is related to insulin resistance but not to obesity in a predominantly obese non-diabetic cohort.

This corrects the article DOI: 10.1038/srep45522.