Biochemical monitoring of 21-hydroxylase deficiency: a clinical utility of overnight fasting urine pregnanetriol.

PURPOSE OF REVIEW: 21-Hydroxylase deficiency (21-OHD), the most common form of congenital adrenal hyperplasia, is an autosomal recessive disorder caused by pathogenic variants in CYP21A2 . Although this disorder has been known for several decades, many challenges related to its monitoring and treatment remain to be addressed. The present review is written to describe an overview of biochemical monitoring of this entity, with particular focus on overnight fasting urine pregnanetriol. RECENT FINDINGS: We have conducted a decade-long research project to investigate methods of monitoring 21-OHD in children. Our latest studies on this topic have recently been published. One is a review of methods for monitoring 21-OHD. The other was to demonstrate that measuring the first morning PT level may be more practical and useful for biochemical monitoring of 21-OHD. The first morning pregnanetriol (PT), which was previously reported to reflect a long-term auxological data during the prepubertal period, correlated more significantly than the other timing PT in this study, with 17-OHP, before the morning medication. SUMMARY: In conclusion, although the optimal method of monitoring this disease is still uncertain, the use of overnight fasting urine pregnanetriol (P3) as a marker of 21-OHD is scientifically sound and may be clinically practical.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

d-allulose protects against diabetic nephropathy progression in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes.

d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats.

Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids.

BACKGROUND & AIMS: Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers. METHODS: During 18-24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g. whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers. RESULTS: The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (ß = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (ß = -0.06; 95% CI: -0.09, -0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, ß = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (ß = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (ß = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol. CONCLUSIONS: Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials. The study was registered at clinicaltrials.gov with NCT00992641.

Use of the Urine-to-Plasma Urea Ratio to Predict ADPKD Progression.

BACKGROUND AND OBJECTIVES: Predicting disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) poses a challenge, especially in early-stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasma urea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression. DESIGN: The urine-to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolonged water deprivation test. Thereafter, association with kidney outcome was evaluated in 583 patients with ADPKD with a broad range of kidney function. Multivariable mixed-model regression was used to assess association with eGFR slope, and logarithmic regression to identify patients with rapidly progressive disease, using a cutoff of -3.0 ml/min per 1.73 m2 per year. The urine-to-plasma urea ratio was compared with established predictors, namely, sex, age, baseline eGFR, Mayo Clinic height-adjusted total kidney volume class, and PKD gene mutation. RESULTS: The maximal urine-concentrating capacity and urine-to-plasma urea ratio correlated strongly (R=0.90; P<0.001). Next, the urine-to-plasma urea ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 (interquartile range, 2.6-5.0) years, both crude and after correction for established predictors (ß=0.58; P=0.02). The odds ratio of rapidly progressive disease was 1.35 (95% confidence interval, 1.19 to 1.52; P<0.001) for every 10 units decrease in urine-to-plasma urea ratio, with adjustment for predictors. A combined risk score of the urine-to-plasma urea ratio, Mayo Clinic height-adjusted total kidney volume class, and PKD mutation predicted rapidly progressive disease better than each of the predictors separately. CONCLUSIONS: The urine-to-plasma urea ratio, which is calculated from routine laboratory measurements, predicts disease progression in ADPKD in addition to other risk markers. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_27_CJN10470620_final.mp3.

Simplified and improved fluid deprivation test for diagnosing diabetes insipidus.

OBJECTIVE: The challenge of finding patients with the rare conditon of diabetes insipidus in need of vasopressin treatment is demanding. The guidelines for performing the fluid deprivation test and interpreting the results are abundant. We evaluated the discriminative capacity of the fluid deprivation test in patients with polyuria to define a cut off for a more effective discrimination between diabetes insipidus and other polyuria syndromes. RESEARCH DESIGN AND METHODS: Retrospective review and data collection of all ambulatory fluid deprivation tests, of patients with mild polyuria and polydipsia (< 3 L/day), performed between 2000 and 2018. Serum osmolality, urine osmolality, urine volumes and clinical information of diagnosis were retrieved from the patient's medical records. RESULTS: The study group consisted of 153 patients, 123 were diagnosed with non-diabetes insipidus and 30 with diabetes insipidus. After 12 h fasting (baseline) median duration of the fluid deprivation test was 5 h (fasting range: 12-21 h). At baseline, there was a significant difference between median serum and urine osmolality between the groups (P < 0.05). The best cut-off for the diagnosis of diabetes insipidus, was the combination of < 400 mosmol/kg in urine and > 302 mosmol/kg in serum. With this cut-off a sensitivity of 90% and specificity of 98% was achieved. CONCLUSION: After 12 h fasting our proposed cut off clearly differentiated between diabetes insipidus, and non-diabetes insipidus suggesting a possibility to considerably reduce the duration of the fluid deprivation test.

An iodine balance study to explore the recommended nutrient intake of iodine in Chinese young adults.

Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the 'iodine overflow' hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 µg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 µg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for µg/d data) and retention (r 0·304 for µg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted ('overflow') through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 µg/d) might be adequate in males, the corresponding level of 61·6 µg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 µg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the 'iodine overflow' hypothesis.

Effect of Cod Residual Protein Supplementation on Markers of Glucose Regulation in Lean Adults: A Randomized Double-Blind Study.

Large quantities of protein-rich cod residuals, which are currently discarded, could be utilized for human consumption. Although fish fillet intake is related to beneficial health effects, little is known about the potential health effects of consuming cod residual protein powder. Fifty lean adults were randomized to consume capsules with 8.1 g/day of cod residual protein (Cod-RP) or placebo capsules (Control group) for eight weeks, in this randomized, double-blind study. The intervention was completed by 40 participants. Fasting glucose and insulin concentrations were unaffected by Cod-RP supplementation, whereas plasma concentrations of α-hydroxybutyrate, ß-hydroxybutyrate and acetoacetate all were decreased compared with the Control group. Trimethylamine N-oxide concentration in plasma and urine were increased in the Cod-RP group compared with the Control group. To conclude, the reduction in these potential early markers of impaired glucose metabolism following Cod-RP supplementation may indicate beneficial glucoregulatory effects of cod residual proteins. Trimethylamine N-oxide appears to be an appropriate biomarker of cod residual protein intake in lean adults.

Simple and non-invasive screening method for diabetes based on myoinositol levels in urine samples collected at home.

OBJECTIVE: To establish a simple screening method for diabetes based on myoinositol (MI) in urine samples collected at home. RESEARCH DESIGN AND METHODS: Initially, we evaluated the stability of urinary MI (UMI) at room temperature (RT; 25°C) and 37°C in 10 outpatients with type 2 diabetes. We then enrolled 115 volunteers without a current or history of diabetes. In all subjects, glucose intolerance was diagnosed by 75 g oral glucose tolerance test (75gOGTT). To assess the association between UMI or urine glucose (UG) and plasma glucose (PG), urine samples were also collected at 0 and 2 hours during 75gOGTT. All the subjects collected urine samples at home before and 2 hours after consuming the commercially available test meal. UMI levels at wake-up time (UMIwake-up), before (UMIpremeal) and 2 hours after the test meal (UMI2h-postprandial) were measured using an enzymatic method. ΔUMI was defined as UMI2h-postprandial minus UMIpremeal. RESULTS: Differing from UG, UMI was stable at RT and 37°C. UMI was increased linearly along with an increase in PG, and no threshold for UMI was observed. UMI was closely associated with blood glucose parameters obtained from a 75gOGTT and hemoglobin A1c (HbA1c) at hospital after adjustment for age, sex, body mass index and serum creatinine. UMIwake-up, UMIpremeal, UMI2h-postprandial and ΔUMI at home were higher in diabetic subjects than non-diabetic subjects even after the above adjustment. Receiver operating characteristics curve (ROC) analyses revealed that for the screening of diabetes, the area under the curve for ROC for UMI2h-postprandial and ΔUMI (0.83 and 0.82, respectively) were not inferior to that for HbA1c ≥48 mmol/mol, which is the American Diabetes Association (ADA) criteria for diabetes. CONCLUSIONS: MI measurement in urine samples collected at home before and after the meal would be a simple, non-invasive and valuable screening method for diabetes.

The Mind-Body Study: study design and reproducibility and interrelationships of psychosocial factors in the Nurses' Health Study II.

PURPOSE: Associations between psychosocial factors and biomarkers are increasingly investigated in studies of cancer incidence and mortality. Documenting optimal data/biospecimen collection protocols and scale properties are fundamental for elucidating the impact of psychosocial factors on biologic systems and ultimately cancer development/progression. METHODS: Between 2013 and 2014, 233 Nurses' Health Study II women (mean age: 60.6) participated in the Mind-Body Study. Participants completed a detailed online psychosocial assessment and provided hair, toenail, timed saliva over 1 day, urine and fasting blood twice, 1 year apart. Additionally, two separate microbiome collections for stool and saliva were conducted between the psychosocial assessments. We assessed correlations between various psychosocial measures and evaluated their 1-year reproducibility using intraclass correlations (ICC). RESULTS: Compliance with the protocols was high among participants. Psychosocial measures showed moderate-to-high reproducibility over 1 year (ICCs = 0.51-0.81). There was clear clustering of psychosocial factors according to whether they were querying positive (e.g., optimism, mastery, mindfulness) or negative (e.g., anxiety, depression, discrimination) emotion-related or social constructs. CONCLUSION: Results suggest feasibility for self-administered collection of various biospecimens and moderate-to-high reproducibility of psychosocial factors. The Mind-Body Study provides a unique resource for assessing inter-relationships between psychosocial factors and biological processes linked with long-term health outcomes, including carcinogenesis.

Urinary bisphenol A concentration and glucose homeostasis in non-diabetic adults: a repeated-measures, longitudinal study.

AIMS/HYPOTHESIS: Bisphenol A (BPA) has been shown to be potentially associated with type 2 diabetes; however, there is little evidence associating BPA exposure with glucose metabolic outcomes prior to diabetes onset. We aimed to examine BPA exposure in relation to glucose homeostasis among non-diabetic individuals. METHODS: This longitudinal cohort study comprised 2336 Chinese adults aged 40 years or above (62.8% women) and free of diabetes at baseline in 2009, followed for 4 years. Urinary BPA and glucose metabolic traits including fasting plasma glucose (FPG), 2 h post-load plasma glucose, fasting serum insulin, HOMA-IR and HOMA-B were measured at baseline and follow-up. Repeated-measures analysis was performed to evaluate associations of urinary BPA concentration with markers of glucose homeostasis. RESULTS: After full adjustment for confounders including BMI, each tenfold increase in urinary BPA concentrations was associated with a 3.39% increase in FPG (95% CI 2.24%, 4.55%) and an 11.6% decrease in HOMA-B (95% CI -15.8%, -7.18%) in women. The inverse association between urinary BPA and HOMA-B was more prominent among overweight or obese individuals (change -13.7%; 95% CI -19.3%, -7.61%) compared with those who were of normal weight (change -6.74%; 95% CI -13.2%, 0.20%) (pinteraction = 0.07). Moreover, the ORs of fasting hyperglycaemia and beta cell dysfunction corresponding to a tenfold increase in urinary BPA concentrations were 1.37 (95% CI 1.10, 1.72) and 1.30 (95% CI 1.02, 1.65) in women, respectively. No significant associations existed between urinary BPA and glucose metabolic markers in men. CONCLUSIONS/INTERPRETATION: Our findings suggest that exposure to BPA was independently associated with impaired glucose homeostasis before the development of diabetes in middle-aged and elderly women.

Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD). STUDY DESIGN: Prospective longitudinal cohort study. SETTING & PARTICIPANTS: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study. PREDICTOR: Fasting urinary osmolality measured using delta cryoscopy. OUTCOMES: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance. ANALYTICAL APPROACH: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR. RESULTS: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile. LIMITATIONS: Fasting was self-reported. CONCLUSIONS: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.

Efficacy of urinary glucose for diabetes screening: a reconsideration.

AIMS: Previous studies indicated that urinary glucose (UG) had a limited efficacy in diabetes screening. This study was designed to have a re-evaluation of its efficacy, taking into consideration the collection method of urine and the measurement approach for UG among Chinese adults. METHODS: This cross-sectional study enrolled a total of 7689 participants without known diabetes, who were fasted and asked to empty bladders before a 75 g glucose loading. Urine was collected 2 h post glucose loading, and UG was measured using quantitative and qualitative approaches. The efficacy of UG in detecting diabetes was assessed by the receiver operating characteristic (ROC) curve. RESULTS: The area under the ROC curve was 0.89 for quantitative UG and 0.87 for qualitative UG. Quantitative UG was positively correlated with fasting plasma glucose (FPG) and 2 h plasma glucose (2 h PG) (r = 0.55 and 0.56, respectively, both P < 0.001). Quantitative UG displayed a sensitivity of 82.9% and a specificity of 84.7% in detecting diabetes at the corresponding optimal cutoff of 130 mg. Qualitative UG exhibited a sensitivity of 80.2% and a specificity of 85.6% at the optimal cutoff of glycosuria + 1. In addition, the sensitivity of both quantitative and qualitative UG was significantly higher than that of HbA1c (≥ 6.5%) (P < 0.001) and had a comparable sensitivity to 2 h PG (≥ 11.1 mmol/L) (P = 0.493). CONCLUSIONS: UG, either quantitatively or qualitatively measured at 2 h post glucose loading, was effective in diabetes screening. This indicates that UG is a feasible approach for diabetes screening.

Impact of Prolonged Fasting on the Risk of Calcium Phosphate Precipitation in the Urine: Calcium Phosphate Lithogenesis during Prolonged Fasting in a Healthy Cohort.

PURPOSE: Intermittent fasting and curtailing water intake for extended periods were likely common in Paleolithic times. Today it occurs for religious and dietary reasons. This restriction in intake should cause a decrease in the urine flow rate while raising the concentration of certain substances in urine to the point of precipitation. In this study we measured the risk of CaHPO4 precipitation following 18 hours of food and water deprivation. MATERIALS AND METHODS: Urine samples were periodically collected from 15 healthy subjects who fasted and abstained from drinking any liquid for 18 hours. The urine constituents Ca2+, HPO42- and pH involved in CaHPO4 formation were measured at various times throughout the fasting day. A comparison was made with control data, which consisted of diurnal urine collections taken throughout a separate nonfasting day prior to the fasting day. RESULTS: The mean ± SEM urine flow rate decreased significantly from 0.93 ± 0.1 ml per minute in the control group to 0.37 ± 0.05 ml per minute in the fasting group (p <0.05). Mean Na+ and Ca2+ excretion rates decreased significantly from 127 ± 12 to 54 ± 13 µmol per minute and from 3.2 ± 0.4 to 0.80 ± 0.21, respectively. Mean urinary Na+ and Ca2+ concentrations also decreased from 161 ± 11.6 to 122 ± 16.0 mmol/l and from 3.7 ± 0.5 to 2.0 ± 0.55, respectively. Urinary pH and the concentration of phosphate, citrate and magnesium were not significantly affected. CONCLUSIONS: Although the steady decrease in the urine flow rate was statistically significant during 18 hours of food and water deprivation, there was no evidence that the calculated risk of CaHPO4 precipitation in the healthy subjects had increased.

Risk of renal stone formation in patients treated with luteinising hormone-releasing hormone analogues for prostate cancer: importance of bone metabolism and urine calcium.

PURPOSE: To determine whether androgen blockade produces metabolic changes in urine and increases the risk of calculi after 1 year of treatment. MATERIALS AND METHODS: The study included 38 patients, from the period April 2015 to June 2016, diagnosed with locally advanced prostate cancer or lymph node metastasis, and with an indication of androgen blockade. Androgen blockade was started with luteinising hormone-releasing hormone (LHRH) analogues, and a blood specimen, a fasting urine and 24-h urine were collected at the time of inclusion, and then at 1 year of follow-up. A study was performed at baseline and at 1 year with imaging tests. An analysis of the variables was performed with a p ≤ 0.05 considered as statistically significant. RESULTS: The mean age of the patients included in the study was 72.26 ± 6.75 years. As regards the biochemistry parameters, an increase in osteocalcin (from 16.28 ± 9.48 to 25.56 ± 12.09 ng/ml; p = 0.001) and an increase in ß-crosslaps (from 0.419 ± 0.177 to 0.743 ± 0.268 ng/ml; p = 0.0001) were observed. In the urinary parameters, a significant increase was observed in the fasting calcium/creatinine ratio (from 0.08 ± 0.06 to 0.13 ± 0.06; p = 0.002) and in the 24-h calcium renal excretion (from 117.69 ± 66.92 to 169.42 ± 107.18 mg; p = 0.0001). Calculi formation was observed in 12 of the 38 patients included (31.6%), with a mean size of 3.33 ± 1.31 mm. CONCLUSION: Treatment with LHRH analogues, as well as increasing the appearance of metabolic syndrome and speeding up the loss bone mineral density, causes an increase in fasting urine calcium.

The effect of intermittent fasting on blood pressure variability in patients with newly diagnosed hypertension or prehypertension.

Intermittent fasting is a phenomenon which can be observed in most humans. The effect of intermittent fasting on blood pressure variability (BPV) has not previously been investigated. The purpose of this study was to assess the effect of fasting on blood pressure (BP) (with office, home, central, and ambulatory blood pressure monitoring [ABPM]) and on BPV. Sixty individuals were included in the study. Office, home, ABPM, and central BP measurements were performed before and during intermittent fasting. Standard deviation and coefficient variation were used for office and home BPV measurement, while the smoothness index was used to calculate ABPM variability. Patients' BP and BPV values before and during intermittent fasting were then compared. Intermittent fasting resulted in a significant decrease in office BP values and ABPM measurements but caused no significant change in home and central BP measurements. Twenty-four hour urinary sodium excretion decreased. Smoothness values obtained from ABPM measurements were low; in other words, BPV was greater. BPV was higher in patients who woke up to eat before sunrise, but BPV was low in patients with high body mass index. Intermittent fasting produced a significant decrease in BP values in terms of office and ABPM measurements in this study but caused no significant change in central BP and home measurements. We also identified an increase in BPV during intermittent fasting, particularly in patients who rose before sunrise.

External validation and comparison of formulae estimating 24-h sodium intake from a fasting morning urine sample.

OBJECTIVE: The relationship between sodium intake and cardiovascular events is controversial, but most large epidemiological studies estimated sodium intake using formulae based on single urine samples, the validity of which is debated. We evaluated sodium intake estimating formulae in a large cohort of adult patients. DESIGN AND METHODS: Patients were asked to collect 24-h urine the day before admission. Validity of the 24-h urine collection was assessed by comparing creatinine clearance from this collection to the mean creatinine clearance from six fractionated urine samples. Only collections with creatinine clearance within ±15% of fractionated clearance were considered valid. The Kawasaki, INTERSALT and Tanaka formulae, using a morning fasting urine sample obtained upon admission, were compared with 24-h urine sodium excretion. The relationship between sodium intake, either measured or estimated, and blood pressure was assessed. RESULTS: Amongst 2278 patients referred to our physiology department between September 2006 and August 2016, 1018 had complete 24-h urine collections and were included in this analysis. Mean age was 51 ±â€Š14 years and mean sodium excretion was 3624 ±â€Š1614 mg/day. The intraclass correlation coefficient was higher for the Kawasaki (0.54; 95% confidence interval, 0.48-0.60), than for the INTERSALT (0.38; 0.33-0.42, P < 0.001), and Tanaka (0.42; 0.37-0.46, P < 0.001) formulae. The Kawasaki formula displayed the lowest mean bias (248; 157-339 mg/day). There was a significant positive association between measured sodium intake and blood pressure, and the Kawasaki formula yielded a similar association. CONCLUSION: All formulae have poor precision and accuracy and are not suitable for estimating individual sodium intake. This does not dismiss their potential value for assessment of sodium intake in population studies.

Pharmacokinetics, Pharmacodynamics, and Safety of Rasagiline Transdermal Patch: A Preliminary Study in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Rasagiline tablet is an oral MAO-B inhibitor applied in early or advanced Parkinson's disease (PD). However, when patients with PD cannot take their usual oral medications, a rasagiline transdermal patch can be used as a way to offer continuous rasagiline while avoiding plasma concentration peaks and troughs. The objectives of this study were to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. METHODS: This single-dose, open-label, randomized, parallel-group study was conducted in 15 healthy subjects. Fasted subjects received a single dose of rasagiline (either by transdermal patch-1.25 mg/24 h, 1.25 mg/48 h, 2.5 mg/48 h, or 2.5 mg/72 h, or orally-in the form of a 1-mg tablet) and were monitored over a 168-h observation period to assess pharmacokinetics, pharmacodynamics, and safety. RESULTS: After administration of a single-dose rasagiline transdermal patch, the mean terminal elimination half-life (t 1/2) was 6.06-9.41 h, which was longer than with the 1-mg tablet dose (2.32 ± 0.28 h). The mean dose-normalized maximum plasma concentration (C max,norm(dose)) of the 1-mg tablet dose was twofold higher than that of the transdermal patch groups. The mean dose-normalized areas under the concentration-time curve (AUCnorm(dose)) of 1.25 and 2.5 mg for the rasagiline transdermal patch doses were fourfold and sevenfold higher than that of the 1-mg tablet dose, respectively. Cumulative urinary excretion was about 0.2% of the total dose. Inhibition of MAO-B activity was dose dependent, and the maximal inhibition was 73.9-94.1% at doses ranging from 1.25 to 2.5 mg. The reported adverse events were mild or moderate. CONCLUSION: The prolonged t 1/2, increased AUC0-t , and more stable plasma drug concentration of the rasagiline patch may permit a longer dosing interval compared to the oral tablet. The rasagiline transdermal patch was safe and well tolerated in healthy Chinese subjects.

Estimation of Chicken Intake by Adults Using Metabolomics-Derived Markers.

BACKGROUND: Improved assessment of meat intake with the use of metabolomics-derived markers can provide objective data and could be helpful in clarifying proposed associations between meat intake and health. OBJECTIVE: The objective of this study was to identify novel markers of chicken intake using a metabolomics approach and use markers to determine intake in an independent cohort. METHODS: Ten participants [age: 62 y; body mass index (in kg/m2): 28.25] in the NutriTech food intake study consumed increasing amounts of chicken, from 88 to 290 g/d, in a 3-wk span. Urine and blood samples were analyzed by nuclear magnetic resonance and mass spectrometry, respectively. A multivariate data analysis was performed to identify markers associated with chicken intake. A calibration curve was built based on dose-response association using NutriTech data. A Bland-Altman analysis evaluated the agreement between reported and calculated chicken intake in a National Adult Nutrition Survey cohort. RESULTS: Multivariate data analysis of postprandial and fasting urine samples collected in participants in the NutriTech study revealed good discrimination between high (290 g/d) and low (88 g/d) chicken intakes. Urinary metabolite profiles showed differences in metabolite levels between low and high chicken intakes. Examining metabolite profiles revealed that guanidoacetate increased from 1.47 to 3.66 mmol/L following increasing chicken intakes from 88 to 290 g/d (P < 0.01). Using a calibration curve developed from the NutriTech study, chicken intake was calculated through the use of data from the National Adult Nutrition Survey, in which consumers of chicken had a higher guanidoacetate excretion (0.70 mmol/L) than did nonconsumers (0.47 mmol/L; P < 0.01). A Bland-Altman analysis revealed good agreement between reported and calculated intakes, with a bias of -30.2 g/d. Plasma metabolite analysis demonstrated that 3-methylhistidine was a more suitable indicator of chicken intake than 1-methylhistidine. CONCLUSIONS: Guanidoacetate was successfully identified and confirmed as a marker of chicken intake, and its measurement in fasting urine samples could be used to determine chicken intake in a free-living population. This trial was registered at clinicaltrials.gov as NCT01684917.