Reference intervals for Sysmex XN hematological parameters as assessed in the Dutch Lifelines cohort

Our aim was to derive reference intervals for all Sysmex XN hematology analyzer parameters. The rationale behind the study was the lack of reference intervals for the XN analyzer cell population data (CPD) and functional parameters. Fresh fasting blood samples from 18,484 participants in the Dutch Lifelines study were analyzed using two automated XN analyzers. Structured health questionnaire data were used to select a subgroup of 15,803 apparently healthy individuals for inclusion in the reference population. The Latent Abnormal Values Exclusion (LAVE) approach was used to reduce the influence of latent diseases in the reference population on the resulting reference intervals. We applied analysis of variance to judge the need for partitioning of the reference intervals by sex or age. We report reference intervals for 105 XN analyzer hematological parameters with and without applying LAVE. Sex-related partitioning was required for red blood cells, (RBC, RBC-O), hemoglobin (HGB, HGB-O), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), reticulocyte production index (RPI), and side scattered light intensity of the red blood cell population in the RET channel (RBC-Z). Partitioning for age was not warranted. Body mass index (BMI) and smoking had moderate influence on a minority of the parameters. We provide reference intervals for all Sysmex XN analyzer routine, CPD and functional parameters, using a direct approach in a large cohort in the Netherlands

Nuclear Magnetic Resonance-Measured Ionized Magnesium Is Inversely Associated with Type 2 Diabetes in the Insulin Resistance Atherosclerosis Study

The aims were to optimize a nuclear magnetic resonance (NMR)-based assay for quantifying ionized or free magnesium and investigate its association with type 2 diabetes (T2D). A high-throughput, ionized magnesium assay was optimized and evaluated. Plasma magnesium was quantified, and associations with T2D were ascertained in Insulin Resistance Atherosclerosis Study (IRAS) participants. Coefficients of variation for the ionized magnesium assay ranged from 0.7–1.5% for intra-assay and 4.2–4.7% for inter-assay precision. In IRAS (n = 1342), ionized magnesium was significantly lower in subjects with prediabetes and T2D than in normoglycemic subjects, and lower in participants with T2D than those with prediabetes (p < 0.0001). Cross-sectional regression analyses revealed that magnesium was associated with T2D at baseline in models adjusted for multiple clinical risk factors (p = 0.032). This association appeared to be modified by sex, in such a way that the associations were present in women (OR = 0.54 (95% CI 0.37–0.79), p = 0.0015) and not in men (OR = 0.98 (95% CI 0.71–1.35), p = 0.90). Longitudinal regression analyses revealed an inverse association between magnesium and future T2D in the total population (p = 0.035) that was attenuated by LP-IR (p = 0.22). No interactions were detected between magnesium and age, race, BMI, glucose, insulin, triglycerides, or LPIR for the prospective association with future T2D. However, a significant interaction between magnesium and sex was present, now with a trend for an association in men (OR = 0.75 (95% CI 0.55–1.02), p = 0.065 and absence of an association in women (OR = 1.01 (0.76–1.33), p = 0.97). Conclusions: lower ionized magnesium, as measured by an NMR-based assay optimized for accuracy and precision, was associated cross-sectionally with T2D at baseline and longitudinally with incident T2D in IRAS

Chronic kidney disease after lung transplantation in a changing era

Lung transplant (LTx) physicians are responsible for highly complex post-LTx care, including monitoring of kidney function and responding to kidney function loss. Better survival of the LTx population and changing patient characteristics, including older age and increased comorbidity, result in growing numbers of LTx patients with chronic kidney disease (CKD). CKD after LTx is correlated with worse survival, decreased quality of life and high costs. Challenges lie in different aspects of post-LTx renal care. First, serum creatinine form the basis for estimating renal function, under the assumption that patients have stable muscle mass. Low or changes in muscle mass is frequent in the LTx population and may lead to misclassification of CKD. Second, standardizing post-LTx monitoring of kidney function and renal care might contribute to slow down CKD progression. Third, new treatment options for CKD risk factors, such as diabetes mellitus, proteinuria and heart failure, have entered clinical practice. These new treatments have not been studied in LTx yet but are of interest for future use. In this review we will address the difficult aspects of post-LTx renal care and evaluate new and promising future approaches to slow down CKD progression.</p

Remnant lipoprotein cholesterol is associated with incident new onset diabetes after transplantation (NODAT) in renal transplant recipients:results of the TransplantLines Biobank and cohort Studies

BACKGROUND: New onset diabetes after transplantation (NODAT) is a frequent and serious complication of renal transplantation resulting in worse graft and patient outcomes. The pathophysiology of NODAT is incompletely understood, and no prospective biomarkers have been established to predict NODAT risk in renal transplant recipients (RTR). The present work aimed to determine whether remnant lipoprotein (RLP) cholesterol could serve as such a biomarker that would also provide a novel target for therapeutic intervention. METHODS: This longitudinal cohort study included 480 RTR free of diabetes at baseline. 53 patients (11%) were diagnosed with NODAT during a median [interquartile range, IQR] follow-up of 5.2 [4.1–5.8] years. RLP cholesterol was calculated by subtracting HDL and LDL cholesterol from total cholesterol values (all directly measured). RESULTS: Baseline remnant cholesterol values were significantly higher in RTR who subsequently developed NODAT (0.9 [0.5–1.2] mmol/L vs. 0.6 [0.4–0.9] mmol/L, p = 0.001). Kaplan-Meier analysis showed that higher RLP cholesterol values were associated with an increased risk of incident NODAT (log rank test, p < 0.001). Cox regression demonstrated a significant longitudinal association between baseline RLP cholesterol levels and NODAT (HR, 2.27 [1.64–3.14] per 1 SD increase, p < 0.001) that remained after adjusting for plasma glucose and HbA1c (p = 0.002), HDL and LDL cholesterol (p = 0.008) and use of immunosuppressive medication (p < 0.001), among others. Adding baseline remnant cholesterol to the Framingham Diabetes Risk Score significantly improved NODAT prediction (change in C-statistic, p = 0.01). CONCLUSIONS: This study demonstrates that baseline RLP cholesterol levels strongly associate with incident NODAT independent of several other recognized risk factors

Reference values for low muscle mass and myosteatosis using tomographic muscle measurements in living kidney donors

Low muscle mass and myosteatosis are associated with poor clinical outcomes. Computed tomography (CT) imaging is an objective method for muscle mass and quality assessment; however consensus on cut-off values is lacking. This study assessed age-, sex-, and body mass index (BMI)-specific reference values of skeletal muscle parameters and correlated muscle mass with 24-h urinary creatinine excretion (24-h UCE). In total, 960 healthy subjects were included in this study. Muscle mass and quality were determined using axial CT slices at the vertebral level L3. The muscle area was indexed for height (skeletal muscle index [SMI]). The mean age was 53 ± 11 years, and 50% were male. The SMI reference values for low muscle mass in males were 38.8 cm2/m2 (20–29 years), 39.2 (30–39 years), 39.9 (40–49 years), 39.0 (50–59 years), 37.0 (60–69 years), and 36.8 (70–79 years). For females, these reference values were 37.5 cm2/m2 (20–29 years), 35.5 (30–39 years), 32.8 (40–49 years), 33.2 (50–59 years), 31.2 (60–69 years), and 31.5 (70–79 years). 24-h UCE and SMI were significantly correlated (r = 0.54, p &lt; 0.001) without bias between the two methods of assessing muscle mass. This study provides age-, sex-, and BMI-specific reference values for skeletal muscle parameters that will support clinical decision making.</p

Circulating de novo lipogenesis fatty acids and all-cause mortality in a prospective Dutch population cohort

Background: Circulating fatty acids (FA) from de novo lipogenesis (DNL) are associated with all-cause mortality in individuals with elevated CVD risk. However, compared to FA early in the DNL synthetic pathway, cis-vaccenic acid, one of the FA distal in the DNL synthetic pathway, has rarely been studied in a general population cohort. We hypothesized that circulating cis-vaccenic acid is more strongly related to all-cause mortality than other circulating DNL-related FA. Objectives: The primary and secondary objectives of this study were to investigate the prospective associations of plasma levels of cis-vaccenic acid and other DNL-related FA with all-cause mortality in a general population, respectively. Methods: We included 850 participants (mean ± SD age 53 ± 15 years) from the Dutch Lifelines cohort study. Circulating levels of palmitic (C16:0), palmitoleic (C16:1n7), cis-vaccenic (cis-C18:1n7), stearic (C18:0), oleic acid (C18:1n9) in plasma phospholipids (PL) and triglycerides (TG) were measured by gas chromatography. The associations of circulating cis-C18:1n7 and other DNL-related FA with all-cause mortality were assessed using Cox regression analyses. Results: During a median follow-up of 9.3 (IQR: 5.4–10.8) years, 34 (4.0%) participants had died. In plasma PL, a 1-SD increase in cis-C18:1n7 was associated with an increased risk of all-cause mortality in univariate and multivariate models (p<0.02 for all), with a HR [95% CI] of 1.60 [1.13–2.25] after adjustment for age and sex. Conclusions: Circulating plasma PL cis-C18:1n7 was associated with a higher risk for all-cause mortality. More studies are needed in different cohorts to verify and validate our results

Plasma phospholipid fatty acid profile, estimated desaturase activities and prevalence of the metabolic syndrome in a general population cohort:A cross-sectional study

BACKGROUND: An altered plasma fatty acid (FA) profile and desaturase activities have been associated with several metabolic diseases, including the MetS, but studies in the general populations are lacking, and only few studies have investigated a broad spectrum of FA in plasma phospholipids (PL). OBJECTIVE: We investigated, cross-sectionally, the relationship of the FA profile and desaturase activities in plasma PL with the prevalence of MetS in a general population in The Netherlands. METHODS: Baseline characteristic data from 850 participants (Male: 50.2%) aged 38-68 years recruited in the Lifelines Cohort study were obtained. The FA profile was determined in fasting plasma PL, and desaturase activities were estimated from product/precursor ratios. The MetS was defined according to International Diabetes Federation. Logistic regressions were used to examine the relation of the FA profile with the prevalence of MetS, and Bonferroni correction was applied to account for multiple testing. RESULTS: 151 participants (17.7%) had the MetS. After adjustment for several confounders and Bonferroni correction, higher tertiles of C18 : 0 (the early precursor of de novo lipogenesis pathway), C18 : 3n6 and C20 : 3n6 (both consistent with a high Δ 6 desaturase (D6D) activity), and D6D activity itself were associated with a higher prevalence of MetS, while higher tertiles of C18 : 1n7, C24 : 0, and C24 : 1n9 (very-long-chain FA) as well as stearoyl-CoA desaturase (SCD)-18 were inversely associated with the MetS. CONCLUSIONS: This study shows that a wide-ranging plasma PL FA profile and estimated desaturase activities were different between adults with and without the MetS in a general representative population and implicates the importance of monitoring individual FAs and desaturase activities as novel modifiable biomarkers for the MetS