Dietary magnesium intake, serum high sensitivity C-reactive protein and the risk of incident knee osteoarthritis leading to hospitalization-A cohort study of 4,953 Finns

Objectives To study whether low dietary magnesium (Mg) intake and serum high sensitivity C-reactive protein (hs-CRP) predict the development of clinical knee osteoarthritis (OA). Methods The cohort consisted of 4,953 participants of a national health examination survey who were free of knee and hip OA at baseline. Information on the incidence of knee OA leading to hospitalization was drawn from the National Care Register for Health Care. During the follow-up of 10 years, 123 participants developed incident knee OA. Dietary magnesium intake was assessed on the basis of a food frequency questionnaire from the preceding year. We used Cox's proportional hazards model to estimate the strength of the association between the tertiles of dietary Mg intake and incident knee OA, adjusted for baseline age, gender, energy intake, BMI, history of physical workload, leisure time physical activity, injuries, knee complaints, the use of Mg supplements, and serum hs-CRP levels. Results At baseline, dietary Mg intake was inversely associated with serum hs-CRP even after adjustment for all the potential confounding factors. During the follow-up, the adjusted hazard ratios (with their 95% confidence intervals) for incident knee OA in dietary Mg intake tertiles were 1.00, 1.28 (0.78-2.10), and 1.38 (0.73-2.62); the p value for trend was 0.31. Serum hs-CRP level at baseline did not predict incident knee OA. Conclusions The results do not support the hypothesis that low dietary Mg intake contributes to the development of clinical knee OA, although Mg intake is inversely associated with serum hs-CRP level.Peer reviewe

Improved accuracy of an tandem liquid chromatography–mass spectrometry method measuring 24R,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D metabolites in serum using unspiked controls and its application to determining cross-reactivity of a chemiluminescent microparticle immunoassay

Measurement of serum 25-hydroxyvitamin D [25(OH)D] is considered the best indicator of vitamin D status. Two minor vitamin D metabolites are common interferences encountered in 25(OH)D assays. The first is 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], which if not chromatographically resolved from 25-hydroxyvitamin D3 [25(OH)D3], can overestimate 25(OH)D concentrations. The second is 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], which can cross-react with the antibodies in 25(OH)D immunoassays. Our aim was to develop an LCâ MS/MS method capable of detecting both 3-epi-25(OH)D3 and 24R,25(OH)2D3 in serum without the use of a derivatization agent. We report an isotope dilution LCâ MS/MS method, with electrospray ionization in the positive mode, that can simultaneously detect 24R,25(OH)2D3, 25(OH)D3, 3-epi-25(OH)D3, and 25-hydroxyvitamin D2. The method employs a cost-effective liquidâ liquid extraction using only 150 μL of sera and a total run time of 10 min. Method performance was assessed by using quality controls made from pooled sera as an alternative to sera spiked with analytes. Biobanked samples, originally analyzed by chemiluminescent microparticle immunoassay (CMIA), were re-analyzed with this method to determine the contribution of 24R,25(OH)2D3 cross-reactivity to 25(OH)D measurement bias. The CMIA over-estimation of 25(OH)D measurements relative to LCâ MS/MS was found to depend on both 25(OH)D and 24R,25(OH)2D3 concentrations

Incidence of liver-related morbidity and mortality in a population cohort of non-alcoholic fatty liver disease

Background & Aims Non-alcoholic fatty liver disease (NAFLD) increases morbidity and mortality. However, patients in biopsy-based cohorts are highly selected and the absolute risks of liver- and non-liver outcomes in NAFLD in population remains undefined. We analysed both liver-related and non-liver-related outcomes in Finnish population cohorts of NAFLD. Methods We included 10 993 individuals (6707 men, mean age 53.3 +/- 12.6 years) with NAFLD (fatty liver index >= 60) from the Finnish population-based FINRISK and Health 2000 studies. Liver fibrosis was assessed by the dAAR score, and genetic risk by a recent polygenic risk score (PRS-5). Incident liver-related outcomes, cardiovascular disease (CVD), cancer and chronic kidney disease (CKD) were identified through linkage with national registries. Results Mean follow-up was 12.1 years (1128 069 person-years). The crude incidence rate of liver-related outcomes in NAFLD was 0.97/1000 person-years. The cumulative incidence increased with age, being respectively 2.4% and 1.5% at 20 years in men and women aged 60 years at baseline, while the relative risks for CVD and cancer were 9-16 times higher. The risk of CKD exceeded that of liver outcomes at a baseline age around 50 years. 20-year cumulative incidence of liver-related outcomes was 4.3% in the high, and 1.5% in the low PRS-5 group. The dAAR score associated with liver outcomes, but not with extra-hepatic outcomes. Conclusion The absolute risk of liver-related outcomes in NAFLD is low, with much higher risk of CVD and cancer, emphasizing the need for more individualized and holistic risk-stratification in NAFLD.Peer reviewe

Low-grade inflammation in first-episode psychosis is determined by increased waist circumference

Psychosis is associated with low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP), a risk factor for cardiovascular events and mortality in the general population. We investigated the relationship between hs-CRP and anthropometric and metabolic changes in first-episode psychosis (FEP) during the first treatment year. We recruited 95 FEP patients and 62 controls, and measured longitudinal changes in hs-CRP, weight, waist circumference, insulin resistance, and lipids. We used linear mixed models to analyze the longitudinal relationship between hs-CRP and clinical, anthropometric and metabolic measures. At baseline, patients with FEP had higher levels of insulin resistance, total and low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Baseline weight, waist circumference, hs-CRP, fasting glucose, and high-density lipoprotein cholesterol were similar between patients and controls. Marked increases in anthropometric measures and hs-CRP were observed in FEP during the 12-month follow-up. However, glucose and lipid parameters did not change significantly. In the mixed models, waist circumference and female sex were significant predictors of hs-CRP levels in FEP. Prevention of the early development of abdominal obesity in FEP is crucial, as abdominal obesity is accompanied by chronic low-grade inflammation, which increases further the cardiovascular risk in this vulnerable population.Peer reviewe

Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity

We examined the association between plasma 25-hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested case-control study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentration was measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.Peer reviewe

Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

Peer reviewe

Serum lipopolysaccharide neutralizing capacity in ischemic stroke.

Introduction Periodontitis is associated with increased serum lipopolysaccharide (LPS) activity, which may be one mechanism linking periodontitis with the risk of cardiovascular diseases. As LPS-carrying proteins including lipoproteins modify LPS-activity, we investigated the determinants of serum LPS-neutralizing capacity (LPS-NC) in ischemic stroke. The association of LPS-NC and Aggregatibacter actinomycetemcomitans, a major microbial biomarker in periodontitis, was also investigated. Materials and methods The assay to measure LPS-NC was set up by spiking serum samples with E. coli LPS. The LPS-NC, LPS-binding protein (LBP), soluble CD14 (sCD14), lipoprotein profiles, apo(lipoprotein) A-I, apoB, and phospholipid transfer protein (PLTP) activity, were determined in 98 ischemic stroke patients and 100 age- and sex-matched controls. Serum and saliva immune response to A. actinomycetemcomitans, its concentration in saliva, and serotype-distribution were examined. Results LPS-NC values ranged between 51-83% in the whole population. Although several of the LPS-NC determinants differed significantly between cases and controls (PLTP, sCD14, apoA-I, HDL-cholesterol), the levels did not (p = 0.056). The main determinants of LPS-NC were i) triglycerides (beta = -0.68, p Conclusion Serum LPS-NC comprised low PLTP-activity, triglyceride and LDL cholesterol concentrations, as well as high HDL cholesterol and IgG against A. actinomycetemcomitans. The present findings let us to conclude that LPS-NC did not associate with stroke.Peer reviewe