Dynamics of serum levels and reference ranges of copeptin in the 3rd trimester of pregnancy in healthy pregnant women with uncomplicated pregnancy and delivery.

OBJECTIVE: Copeptin is a stable fragment of vasopressin. Copeptin levels have been found to reflect the degree of endothelial stress in various conditions, including acute coronary syndrome. Copeptin may be a bio marker for endothelial stress during pregnancy. However, there is still a lack of understanding of its dynamics and levels throughout pregnancy. This study aims to describe intra-individual and longitudinal changes in copeptin levels at 30th and 36th gestational weeks in healthy pregnant women with uncomplicated pregnancy and delivery and to establish specific reference ranges. METHODS: A total of 125 pregnant women with uncomplicated pregnancy and delivery were included. These women were monitored throughout their pregnancy and gave birth at the Department of Obstetrics and Gynecology Olomouc University Hospital. The blood was taken at ~30 and ~36 gestational weeks. Serum copeptin levels were measured using a Kryptor Compact PLUS analyzer. For statistics, we used R software and the "referenceRanges" package. RESULTS: It was found that serum levels of copeptin were significantly higher in the 36th week group than in the 30th week group (P < 0.05). Cook's distance was used to eliminate outliers. The 30th week median was 3.377 pmol/l, reference range = 1.343-7.829 pmol/l, and the 36 week was median 4.735 pmol/l and reference range = 2.06-13.2 pmol/l. In the 36th week reference range, the median was higher than in healthy, non-pregnant women (P < 0.05). Copeptin values can exceed 10 pmol/l, particularly after the 36th week. In the 3rd trimester, this value may indicate cardiovascular and endothelial overload. CONCLUSION: Copeptin levels were found to vary significantly depending on gestational week. The proposed reference ranges take into account the increased secretion of vasopressin in pregnancy. The existence of specific upper reference limits represents a potential advantage in detecting pregnant women prone to hypertensive disease in the 3rd trimester.

Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

BACKGROUND: There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. METHODS: We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. RESULTS: We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. CONCLUSIONS: Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

Biological Variation Estimates for Plasma Copeptin and Clinical Implications.

BACKGROUND: Plasma copeptin measurement is useful for the differential diagnoses of polyuria-polydipsia syndrome. It has also been proposed as a prognostic marker for cardiovascular diseases. However, limited information is available about the within- (CVI) and between-subject (CVG) biological variation (BV). This study presents BV estimates for copeptin in healthy individuals. METHODS: Samples were collected weekly from 41 healthy subjects over 5 weeks and analyzed using the BRAHMS Copeptin proAVP KRYPTOR assay after at least 8 h of food and fluid abstinence. Outlier detection, variance homogeneity, and trend analysis were performed followed by CV-ANOVA for BV and analytical variation (CVA) estimation with 95% confidence intervals. Reference change values (RCVs), index of individuality (II), and analytical performance specification (APS) were also calculated. RESULTS: The analysis included 178 results from 20 males and 202 values from 21 females. Copeptin concentrations were significantly higher in males than in females (mean 8.5 vs 5.2 pmol/L, P < 0.0001). CVI estimates were 18.0% (95% CI, 15.4%-21.6%) and 19.0% (95% CI, 16.4%-22.6%), for males and females, respectively; RCVs were -35% (decreasing value) and 54% (increasing value). There was marked individuality for copeptin. No result exceeded the diagnostic threshold (>21.4 pmol/L) for arginine vasopressin resistance. CONCLUSIONS: The availability of BV data allows for refined APS and associated II, and RCVs applicable as aids in the serial monitoring of patients with specific diseases such as heart failure. The BV estimates are only applicable in subjects who abstained from oral intake due to the rapid and marked effects of fluids on copeptin physiology.

Association of copeptin levels with patient prognosis and survival in sepsis syndromes: a meta-analysis.

BACKGROUND: Sepsis syndromes are a major burden in the ICU with very high mortality. Vasopressin and copeptin are released in response to hypovolemia and have shown potential significance in diagnosing sepsis. OBJECTIVE: To investigate the levels of copeptin in patients with sepsis syndromes and evaluate its relation with patient prognosis and mortality. METHODS: Four databases were searched for literature published from inception to the 8th of November 2022. Original research articles where copeptin was measured in sepsis patients and compared with controls were included. Data extraction and synthesis: study characteristics, levels of copeptin in the participants, and copeptin assay description were extracted. Levels of copeptin in patients were pooled and compared with controls in terms of the standard mean difference (SMD) generated using a random-effects model. RESULTS: Fifteen studies met the selection criteria. Copeptin levels were significantly higher in patients with sepsis, severe sepsis, and septic shock as compared to controls [(SMD: 1.49, 95% CI: 0.81-2.16, P<0.0001), (SMD: 1.94, 95% CI: 0.34-3.54, P=0.02), and (SMD: 2.17, 95% CI: 0.68-3.66, P=0.004), respectively]. The highest copeptin levels were noted in septic shock patients. The admission copeptin levels were significantly lower in survivors as compared to nonsurvivors (SMD: -1.73; 95% CI: -2.41 to -1.06, P<0.001). CONCLUSION AND RELEVANCE: Copeptin was significantly elevated in sepsis, severe sepsis, and septic shock. Survivors had a significantly lower copeptin during admission. Copeptin offered an excellent predictability to predict 1-month mortality. Measuring the copeptin in sepsis patients can aid treating physicians to foresee patients' prognosis.

Food intake, plasma copeptin and cardiovascular risk in patients with type 2 diabetes: A cross-sectional analysis.

BACKGROUND AND AIM: Increased consumption of ultra-processed foods has been linked to both mortality and cardiovascular risk. Copeptin levels may serve as potential risk markers for cardiovascular death and events. This cross-sectional analysis seeks to assess the potential correlation between the intake of ultra-processed foods and copeptin levels in outpatients diagnosed with type 2 diabetes, based on estimates of cardiovascular risk. METHODS AND RESULTS: Outpatients underwent clinical and nutritional assessments. Dietary information was gathered using a validated quantitative food frequency questionnaire, and the consumption of all foods, beverages, and food products was assessed according to the NOVA food classification system. Fasting plasma-EDTA samples were collected and preserved at -80 °C. Plasma copeptin measurements were analyzed using an enzyme-linked immunosorbent assay based on the competition principle. Participants were categorized into two groups: high risk and very high risk, based on cardiovascular risk calculated by the HEARTS calculator. A total of 190 participants were included in the evaluation, with an average age of 60 ± 9 years, glycated hemoglobin of 8.4 ± 1.4%, and a diabetes duration of 11 (5-19) years. Patients at a very high cardiovascular risk exhibited higher plasma copeptin levels compared to those at high cardiovascular risk. Notably, 92.1% of patients reported consuming more than 10% of total energy intake from ultra-processed foods, although this proportion did not differ between the two groups. CONCLUSION: This patient sample reported elevated consumption of ultra-processed foods; nevertheless, the correlation between ultra-processed foods and plasma copeptin has not been substantiated.

Evaluation of copeptin in children after stimulation with clonidine or L-Dopa.

OBJECTIVES: Arginine-stimulated serum copeptin has been proposed as a new method to diagnose arginine vasopressin (AVP) deficiency in children and adolescents. Herein we investigated the secretagogic potential of clonidine or L-Dopa on the copeptin serum levels in children. METHODS: Eight stimulation tests (4 with clonidine and 4 with L-Dopa) were performed in eight children (5 boys and 3 girls) with a median age of 6.5 years-old, evaluated for short stature due to possible growth hormone deficiency. Serum copeptin levels were measured at 30, 60, 90, and 120 min after administration of clonidine or L-Dopa. RESULTS: Copeptin levels in serum did not show any significant change in either test (clonidine or L-Dopa). The values of copeptin levels compared to the baseline value did not deviate more than 5 % in the clonidine arm (p=0.60) or 8 % in the L-Dopa arm (p=0.75) respectively. CONCLUSIONS: Data do not support the use of L-Dopa or clonidine as stimulants for evaluating AVP relating disorders in clinical pediatric practice.

The influence of insulin-induced hypoglycemia on copeptin concentrations.

Plasma copeptin is a biomarker that reflects arginine vasopressin (AVP) secretion. In this study we measured copeptin during insulin tolerance test (ITT) in 65 patients referred to our department for evaluation of anterior pituitary function. Plasma for measurements of copeptin were collected at the start of the test and regurarly up to 120 minutes thereafter. Of 60 patients who developed significant hypoglycemia and were included in the analyses, 13 (22%) had corticotropic deficiency, 11 (18%) had thyreotropic deficiency, 33 (55%) had growth hormone deficiency and 4 (6%) had AVP deficieny (AVPD). Thirty-seven (62%) patients had at least one anterior pituitary deficiency. In patients without AVPD, median (range) copeptin increased from 4.5 pmol/L (1.3-33.0) to a maximum of 6.2 pmol/L (2.0-34.4; p<0.001). Baseline copeptin was similar in men and women, but maximal copeptin during ITT was higher in men. Copeptin concentrations were not affected by age, BMI, somatotropic, or corticotropic function. Copeptin concentrations were lower in patients with AVPD than patiets without AVPD, and in patients with thyrotropic deficiency, compared to patients with intact thyrotropic function, both at baseline and during ITT. In conclusion, copeptin increases significantly during insulin induced hypoglycemia but is of limited value in predicting anterior pituitary hormonal function.

The diagnostic role of arginine-stimulated copeptin in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in pediatric age.

PURPOSE: In recent years, copeptin stimulation through arginine administration has been evaluated as a new potential tool in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in adults; to date very few data, all retrospective, exist in pediatric age. The aim of this prospective study is to evaluate the diagnostic performance of the arginine-stimulation test for copeptin in a cohort of pediatric patients affected by PPS. METHODS: All children (<18 years) referred to the Department of Pediatric Endocrinology of the Regina Margherita Children Hospital for polyuria-polydipsia in the period January 2021-June 2023 were enrolled. The Arginine-stimulation test for copeptin was performed in all patients presenting PPS after water deprivation test (WDT). Patients with polyuria-polydipsia were then classified as having primary polyuria (PP), complete and partial central diabetes insipidus (CDI), according to the standardized interpretation. Arginine-stimulation test for copeptin was also performed in a control cohort. RESULTS: A significant difference in arginine-stimulated copeptin values was observed at baseline (p = 0.005), at 60 min (p = 0.01), and at 90 min (p = 0.005) in 7 subjects presenting PP, 6 patients affected by CDI and 50 subjects of the control cohort. Plasma osmolality values remained stable at all measurements. The arginine-stimulated copeptin test demonstrated sensitivity and specificity of 100%, whereas the sensitivity of the WDT test was 83.3% and the specificity was 85.7%. CONCLUSION: Given the reliability and the minor adverse effects and costs, the copeptin level after arginine administration could replace the WDT in the diagnostic workup of these in pediatric age.

Short-term association between outdoor temperature and the hydration-marker copeptin: a pooled analysis in five cohorts.

BACKGROUND: Whereas outdoor temperature is linked to both mortality and hydration status, the hormone vasopressin, measured through the surrogate copeptin, is a marker of cardiometabolic risk and hydration. We recently showed that copeptin has a seasonal pattern with higher plasma concentration in winter. Here, we aimed to investigate the association between outdoor temperature and copeptin. METHODS: Copeptin was analysed in fasting plasma from five cohorts in Malmö, Sweden (n = 26,753, 49.7% men, age 18-86 years). We utilized a multivariable adjusted non-linear spline model with four knots to investigate the association between short-term temperature (24 h mean apparent) and log copeptin z-score. FINDINGS: We found a distinct non-linear association between temperature and log copeptin z-score, with both moderately low and high temperatures linked to higher copeptin concentration (p < 0.0001). Between 0 °C and nadir at the 75th temperature percentile (corresponding to 14.3 °C), log copeptin decreased 0.13 z-scores (95% CI 0.096; 0.16), which also inversely corresponded to the increase in z-score log copeptin between the nadir and 21.3 °C. INTERPRETATION: The J-shaped association between short-term temperature and copeptin resembles the J-shaped association between temperature and mortality. Whereas the untangling of temperature from other seasonal effects on hydration warrants further study, moderately increased water intake constitutes a feasible intervention to lower vasopressin and might mitigate adverse health effects of both moderately cold and hot outdoor temperatures. FUNDING: Swedish Research Council, Å Wiberg, M Stephen, A Påhlsson, Crafoord and Swedish Heart-Lung Foundations, Swedish Society for Medical Research and Swedish Society of Medicine.

Copeptin is associated with microalbuminuria and renal function in the general Japanese population.

An association between copeptin (precursor molecule of arginine vasopressin) and markers for renal function has been reported, but data on the Japanese population has been limited. In this study, we investigated whether elevated copeptin levels are associated with microalbuminuria and renal dysfunction in the general Japanese population. A total of 1,262 participants (842 female and 420 male) were enrolled. Multiple regression analysis was performed to assess the association of copeptin levels (logarithm) with estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR) after adjusting for age, BMI, and lifestyle variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression methods in which chronic kidney disease (CKD) was the dependent variable. The copeptin levels differed significantly with sex, but were not found to be related to age or the span of time from preceding meal to blood sampling. In female participants, copeptin level was negatively correlated with eGFR (beta = -0.100, p-value = 0.006) and positively correlated with UACR (beta = 0.099, p-value = 0.003). In male participants, a negative correlation (beta = -0.140, p-value = 0.008) was observed for eGFR. In both females and males, those with high copeptin levels had more than double the ORs of CKD (OR = 2.1-2.9) adjusted for CKD-related factors. The present study found elevated copeptin levels to be associated with renal function loss in the Japanese population and microalbuminuria in female. Moreover, it was evident that high copeptin levels are associated with CKD. These results suggest that copeptin could be considered a marker of renal function.

Serum Copeptin in Cardiooncology Practice: Review of Pathophysiological and Clinical Implications.

In cardiooncology practice, "early cardiotoxicity" refers to an emerging subclinical myocardial dysfunction/injury in response to certain chemotherapeutic regimens. This condition can progress to overt cardiotoxicity in time and hence warrants proper and timely diagnostic and preventive strategies. Current diagnostic strategies for "early cardiotoxicity" are largely based on conventional biomarkers and certain echocardiographic indices. However, a significant gap still exists in this setting, warranting further strategies to improve diagnosis and overall prognosis in cancer survivors. Copeptin (surrogate marker of the arginine vasopressine axis) might serve as a promising adjunctive guide for the timely detection, risk stratification, and management of early cardiotoxicity on top of conventional strategies largely due to its multifaceted pathophysiological implications in the clinical setting. This work aims to focus on serum copeptin as a marker of "early cardiotoxicity" and its general clinical implications in patients with cancer.

Changed serum levels of CD62E+, angiotensin II and copeptin in patients with chronic insomnia disorder: a link between insomnia and stroke?

BACKGROUND: Epidemiological and observational clinical studies have found that insomnia is a risk factor for stroke and that, accordingly, insomnia is likely to cause changes of stroke-related biomarkers. There is substantial evidence that stroke is closely related to endothelial dysfunction and hypertension. The aim of this study is to investigate whether there is alteration of endothelial dysfunction (CD62E+) and hypertension (angiotensin II and copeptin) biomarkers in patients with chronic insomnia disorder (CID). METHODS: The CID patients (N = 54) and the good sleepers (GS, N = 32) were enrolled. Pittsburgh sleep quality index (PSQI), pre-sleep arousal scale (PSAS) and polysomnography were used to assess their sleep and neuropsychological function. Serum levels of CD62E+, angiotensin II and copeptin were determined using a quantitative sandwich ELISA. RESULTS: The CID group had higher serum levels of CD62E+, angiotensin II, and copeptin than the GS group. After controlling for sex, age, depression and apnea-hypopnea index, the partial correlation analysis revealed that the levels of CD62E+ and copeptin correlated positively with the PSAS score and negatively with the objective sleep quality. Angiotensin II levels negatively correlated with objective sleep onset latency. Moreover, there was a positive correlation between CD62E+ and angiotensin II. Principal components analysis revealed that CD62E+ and copeptin had a substantial correlation with parameters of subjective and objective sleep. CONCLUSION: Patients with CID exhibit endothelial activation, over-activated renin-angiotensin system and increased sympathetic excitability, as indicated by increased serum levels of CD62E+, angiotensin II and copeptin, with linking to poor sleep quality.

Biomarkers-in-Cardiology 8 RE-VISITED-Consistent Safety of Early Discharge with a Dual Marker Strategy Combining a Normal hs-cTnT with a Normal Copeptin in Low-to-Intermediate Risk Patients with Suspected Acute Coronary Syndrome-A Secondary Analysis of the Randomized Biomarkers-in-Cardiology 8 Trial.

Regarding the management of suspected Non-ST-segment-elevation acute coronary syndrome (ACS), the main Biomarker-in-Cardiology (BIC)-8 randomized controlled trial study had reported non-inferiority for the incidence of major adverse cardiac events at 30 days in the Copeptin group (dual marker strategy of copeptin and hs-cTnT at presentation) compared to the standard process (serial hs-cTnT testing). However, in 349 (38.7%) of the 902 patients, high-sensitivity cardiac troponin was not available for the treating physicians. High sensitivity cardiac troponin T was re-measured from thawed blood samples collected at baseline. This cohort qualified for a re-analysis of the 30-day incidence rate of MACE (death, survived cardiac death, acute myocardial infarction, re-hospitalization for acute coronary syndrome, acute unplanned percutaneous coronary intervention, coronary bypass grafting, or documented life-threatening arrhythmias), or components of the primary endpoint including death or death/MI. After re-measurement of troponin and exclusion of 9 patients with insufficient blood sample volume, 893 patients qualified for re-analysis. A total of 57 cases were detected with high sensitivity cardiac troponin T ≥ 14 ng/L who had been classified as "troponin negative" based on a conventional cardiac troponin T or I < 99th percentile upper limit of normal. Major adverse cardiac events rates after exclusion were non-inferior in the Copeptin group compared to the standard group (4.34% (95% confidence intervals 2.60-6.78%) vs. 4.27% (2.55-6.66%)). Rates were 53% lower in the per-protocol analysis (HR 0.47, 95% CI: 0.18-1.15, p = 0.09). No deaths occurred within 30 days in the discharged low risk patients of the Copeptin group. Copeptin combined with high sensitivity cardiac troponin is useful for risk stratification and allows early discharge of low-to-intermediate risk patients with suspected acute coronary syndrome is as safe as a re-testing strategy at 3 h or later.

Improvement of outcome prediction of hospitalized patients with COVID-19 by a dual marker strategy using high-sensitive cardiac troponin I and copeptin.

BACKGROUND: COVID-19 has been associated with a high prevalence of myocardial injury and increased cardiovascular morbidity. Copeptin, a marker of vasopressin release, has been previously established as a risk marker in both infectious and cardiovascular disease. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from June 6th to November 26th, 2020 in a tertiary care hospital. Copeptin and high-sensitive cardiac troponin I (hs-cTnI) levels on admission were collected and tested for their association with the primary composite endpoint of ICU admission or 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included of whom 55 (25.8%) reached the primary endpoint. Median levels of copeptin and hs-cTnI at admission were significantly higher in patients with an adverse outcome (Copeptin 29.6 pmol/L, [IQR, 16.2-77.8] vs 17.2 pmol/L [IQR, 7.4-41.0] and hs-cTnI 22.8 ng/L [IQR, 11.5-97.5] vs 10.2 ng/L [5.5-23.1], P < 0.001 respectively). ROC analysis demonstrated an optimal cut-off of 19.3 pmol/L for copeptin and 16.8 ng/L for hs-cTnI and an increase of either biomarker was significantly associated with the primary endpoint. The combination of raised hs-cTnI and copeptin yielded a superior prognostic value to individual measurement of biomarkers and was a strong prognostic marker upon multivariable logistic regression analysis (OR 4.274 [95% CI, 1.995-9.154], P < 0.001). Addition of copeptin and hs-cTnI to established risk models improved C-statistics and net reclassification indices. CONCLUSION: The combination of raised copeptin and hs-cTnI upon admission is an independent predictor of ICU admission or 28-day mortality in hospitalized patients with COVID-19.

Copeptin: Prognostic Relevance as a Perioperative Marker in Pediatric Cardiac Surgery.

BACKGROUND: Copeptin is a cleavage product of vasopressin. This study aimed to figure out if copeptin would be a suitable biomarker in patients with congenital heart disease in the postoperative course. METHODS: The primary outcome endpoint of this study was the change in copeptin concentration perioperatively in patients with congenital heart disease after surgery, with the use of a cardiopulmonary bypass. Three blood samples were taken from 81 patients up to 6 years of age in order to evaluate changes in copeptin concentration. RESULTS: Significant increase of copeptin concentration was shown between the first and second blood draws as well as between the first and third blood draws (Ps < .001). Additionally, positive and significant correlations (r ≥ .27) between the cardiopulmonary bypass times, The Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery mortality category, the inotropic score, the duration of mechanical ventilation, the length of stay at the intensive care unit (ICU), the length of stay at the hospital, and the preoperative as well as the ICU copeptin levels were found. CONCLUSIONS: Copeptin showed a tendency to predict the clinical outcome of patients after congenital heart surgery. Patients with higher copeptin levels underwent more complex procedures, had longer cardiopulmonary bypass times, required more catecholamine support, needed longer time of invasive ventilation, and had longer overall stay and ICU stay.

Increased Circulating Copeptin Levels Are Associated with Vaso-Occlusive Crisis and Right Ventricular Dysfunction in Sickle Cell Anemia.

OBJECTIVE: Vaso-occlusive crisis (VOC) is a common clinical manifestation of sickle cell anemia (SCA) and is associated with increased proinflammatory mediators. Copeptin is the C-terminal part of the prohormone for provasopressin and seems clinically relevant in various clinical conditions. Right ventricular (RV) dysfunction significantly appears in SCA patients due to pulmonary hypertension. This study aimed to investigate the association of copeptin levels in VOC patients and evaluate RV dysfunction. MATERIALS AND METHODS: A total of 108 patients were enrolled in the study. Twenty-eight SCA patients in steady state (30.2 ± 0.9 years), 25 SCA patients in VOC (36.8 ± 11.8 years), and 55 healthy individuals (31.9 ± 9.4 years) with HbAA genotype were included. Clinical, echocardiographic, and laboratory data were recorded. ELISA was used for the determination of serum levels of copeptin. RESULTS: VOC patients had significantly higher copeptin level compared both with controls and SCA subjects in steady state (22.6 ± 13.0 vs. 11.3 ± 5.7 pmol/L, 22.6 ± 13.0 vs. 12.4 ± 5.8 pmol/L, p = 0.009 for both). Additionally, the copeptin level was significantly higher in SCA patients with RV dysfunction than those without RV dysfunction (23.2 ± 12.2 vs. 15.3 ± 9.5 pmol/L, p = 0.024). Multiple logistic regression analysis revealed that high-sensitivity C-reactive protein and copeptin levels were found to be associated with VOC. CONCLUSION: This study showed that copeptin and hs-CRP levels were increased in patients with VOC, and it was found that RV dysfunction was more common in SCA patients with VOC than in the control group. Copeptin can be considered for use as a potential biomarker in predicting VOC crisis in SCA patients and in the early detection of patients with SCA who have the potential to develop RV dysfunction.

Investigation of possible underlying mechanisms behind water-induced glucose reduction in adults with high copeptin.

Elevated copeptin, a surrogate marker of vasopressin, is linked to low water intake and increased diabetes risk. Water supplementation in habitual low-drinkers with high copeptin significantly lowers both fasting plasma (fp) copeptin and glucose. This study aims at investigating possible underlying mechanisms. Thirty-one healthy adults with high copeptin (> 10.7 pmol·L-1 (men), > 6.1 pmol-1 (women)) and 24-h urine volume of < 1.5L and osmolality of > 600 mOsm·kg-1 were included. The intervention consisted of addition of 1.5 L water daily for 6 weeks. Fp-adrenocorticotropic hormone (ACTH), fp-cortisol, 24-h urine cortisol, fasting and 2 h (post oral glucose) insulin and glucagon were not significantly affected by the water intervention. However, decreased (Δ baseline-6 weeks) fp-copeptin was significantly associated with Δfp-ACTH (r = 0.76, p < 0.001) and Δfp-glucagon (r = 0.39, p = 0.03), respectively. When dividing our participants according to baseline copeptin, median fp-ACTH was reduced from 13.0 (interquartile range 9.2-34.5) to 7.7 (5.3-9.9) pmol L-1, p = 0.007 in the top tertile of copeptin, while no reduction was observed in the other tertiles. The glucose lowering effect from water may partly be attributable to decreased activity in the hypothalamic-pituitary-adrenal axis.ClinicalTrials.gov: NCT03574688.

Parathyroid Hormone Resistance and Autoantibodies to the PTH1 Receptor.

We describe two cases of acquired parathyroid hormone (PTH) resistance consequent to the development of serum PTH type 1 receptor (PTH1R) autoantibodies, which block PTH binding and signaling. Both cases were associated with other autoimmune manifestations, and one case was associated with atypical membranous glomerulonephritis. In vitro binding and signaling assays identified the presence of PTH1R-blocking IgG autoantibodies, which were not present in serum samples from patients with other renal or autoimmune disorders. (Funded by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis.

Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics.

The additive value of copeptin for early diagnosis and prognosis of acute coronary syndromes.

BACKGROUND: One promising biomarker that has received substantial interest for the evaluation of suspected acute coronary syndromes (ACS) is copeptin. Therefore, our goal was to assess the additive value of copeptin for early diagnosis and prognosis of Non-ST segment acute coronary syndromes (NSTE-ACS). METHODS: The study included ninety patients with suspected ACS. Patients with typical ischemic chest pain within six hours of symptom onset and without ST-segment elevation on electrocardiograph (ECG) were included. In addition to cardiac troponin I (cTnI), copeptin was assayed from venous blood samples obtained on admission, followed by serial troponin measurements six and twelve hours later. One year follow-up was performed for any major adverse cardiac events (MACEs) including cardiac death, re-infarction, re- hospitalization for ischemic events, heart failure, stroke and target lesion revascularization (TLR). RESULTS: Of seventy nine patients included in the final analysis, Forty (50.6%) were diagnosed as unstable angina (UA), while thirty nine (49.4%) had a non-ST elevation myocardial infarction (NSTEMI). Copeptin level on admission was significantly higher among NSTEMI patients than those with UA. With regard to the correlation analyses, copeptin was positively correlated with each of, Global Registry of Acute Coronary Events (GRACE), Thrombolysis In Myocardial Infarction (TIMI) and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) scores. The sensitivity and negative predictive value (NPV) of the combination of admission copeptin and cTn-I were 100% and 100%, respectively, versus 57% and 70%, respectively, with admission of cTn-I alone. The area under curve (AUC) of the combination of copeptin and cTn-I was (0.975, p < 0.001) and was significantly higher than the AUC of cTn-I alone (0.888, p < 0.001). Admission copeptin was an independent predictor for MACEs by multiple regression analysis (OR: 0.01, 95% CI: 0.0-0.8, P = 0.04). High values of copeptin had the highest rate of MACEs and coronary revascularization during one year of follow up. CONCLUSION: The combination of copeptin and conventional troponin I aids in early rule out of NSTEMI virtually independent of chest pain onset (CPO) with high NPV in patients presenting within three hours from chest pain onset with excellent prognostic value for risk stratification and prediction of MACEs.