DOCSLIB.ORG

Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney Disease Kidney360 Publish Ahead of Print, published on July 8, 2021 as doi:10.34067/KID.0002622021 Peripheral insulin resistance is associated with copeptin in patients with chronic kidney disease Juan Pablo Arroyo1*, Elvis A. Akwo1*, Andrew S. Terker1, Aseel Alsouqi1, Gautam Bhave1, Raymond C. Harris1, Adriana M. Hung1, T. Alp Ikizler1 1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee * These authors contributed equally Address correspondence to: T. Alp Ikizler M.D. Division of Nephrology Vanderbilt University Medical Center S-3223 Medical Center North 1161 21st Ave South Nashville, TN 37232-2372 Phone 615-343-2220 | Fax 615-343-7156 Copyright 2021 by American Society of Nephrology. Key Points We found that in non-diabetic patients with CKD 3-4 elevated levels of copeptin are associated with peripheral insulin resistance. We found no correlation between copeptin levels and hepatic insulin resistance in patients with CKD 3-4 or in our control group. Further research is warranted to establish potential mechanistic links between vasopressin and peripheral insulin resistance in CKD. Abstract Background – Insulin resistance is associated to cardiovascular disease risk and worsened kidney function. Patients with CKD have higher levels of insulin resistance. Elevated levels of copeptin (a surrogate for vasopressin levels), has been associated to increased incidence and progression of CKD as well as incident diabetes mellitus. The purpose of our study was to study the relationship between insulin resistance, copeptin, and CKD. Methods - We performed a cross-sectional study to investigate if insulin resistance was associated with higher copeptin levels in non-diabetic patients with stage 3-4 CKD vs controls. We measured plasma copeptin levels and utilized data from 52 patients with stage 3-4 CKD and 85 controls (eGFR ≥ 60mL/min/1.73m2) enrolled in The Insulin Resistance in Chronic Kidney Disease (IRCKD) study. We then used a multivariable linear regression model to assess the independent relationship between peripheral or hepatic insulin resistance and copeptin across levels of eGFR. Results – We found that in patients with CKD (eGFR 30-60 mL/min/1.73m2), but not in controls, peripheral insulin resistance was significantly correlated with higher levels of log copeptin (r = - 0.21, p = 0.04). In patients with CKD when adjusted for age, sex, BMI, serum osmolality, log IL6, and log leptin-adiponectin ratio, each 1 SD decrease in insulin sensitivity was associated to a 38.9% increase in serum copeptin levels. The relationship between hepatic insulin resistance, copeptin, and eGFR is similar between controls and patients with reduced eGFR. Conclusion –Peripheral insulin resistance is associated with elevated copeptin levels in non- diabetic patients with stage 3-4 CKD. Further research into how the interaction between peripheral insulin resistance and elevated vasopressin impacts CKD progression could be of interest. Introduction Patients with CKD have more insulin resistance (IR) than what is observed in matched individuals without kidney disease.1 Prior data suggests that insulin resistance can hasten the development of kidney disease.2 Moreover, insulin resistance is associated with cardiovascular disease risk and this relationship is magnified in patients with CKD.3 Therefore, mechanistic insights into how insulin resistance and CKD interact could have far-reaching implications and aid in the development of novel therapeutic strategies. The etiology of insulin resistance seen in patients with CKD is believed to be multifactorial including genetic variants, physical inactivity, inflammation, oxidative stress, and adipokine derangements. Insulin resistance in CKD is driven primarily by defective glucose uptake in fat and skeletal muscle, but the identification of discrete, modifiable signaling pathways has remained elusive. 1, 4 Vasopressin is the nine amino-acid peptide hormone end-product of a highly processed 164 amino acid pre-pro-peptide. Vasopressin levels are elevated in patients with CKD, however the mechanisms that lead to elevated vasopressin levels remain incompletely explained.5 High vasopressin levels have been associated with both increased incidence and progression of CKD from various etiologies. 6-8 Elevated levels of copeptin (the C-terminal product of the vasopressin precursor protein, a surrogate for vasopressin levels) correlate with albuminuria and incident diabetes mellitus (DM). 6, 9-11 In healthy subjects, the infusion of vasopressin increased plasma glucose and glucose infusion led to decreased vasopressin levels within minutes, despite increased serum osmolality 10-12. More recently, vasopressin has been implicated in the development of fructose-induced metabolic syndrome.13 Together, these data suggest that vasopressin plays a key role in glucose-insulin homeostasis. In spite of the extensive data on the link between vasopressin and glucose homeostasis, whether insulin resistance is associated to elevated levels of vasopressin in patients with CKD has never been studied. We hypothesized that patients with CKD and insulin resistance would have higher copeptin levels than either CKD patients with no insulin resistance or patients with insulin resistance and no CKD. Therefore, we performed a cross-sectional study to investigate if insulin resistance was associated with higher levels of copeptin levels in non-diabetic patients with stage 3-4 CKD vs controls. Methods Design and Study Sample We conducted a cross-sectional study using data from 52 patients with CKD stages 3-4 and 85 controls (eGFR ≥ 60mL/min/1.73m2) enrolled in The Insulin Resistance in Chronic Kidney Disease (IRCKD) study. Study participants were recruited from the Nashville Veterans Affairs (VA) Medical Center and Vanderbilt University Medical Center (VUMC) outpatient clinics. All study participants were non-diabetic and had a body mass index (BMI) greater >18 kg/m2 at enrollment. Diabetes was ascertained based on medical history, anti-diabetic medication use, glycated hemoglobin (≥6.5%) or fasting plasma glucose (FPG ≥126mg/dL). In the CKD group, we included patients aged ≥ 18 years, with eGFR less than 60 mL/min/1.73m2, less that 5g/24 hours of proteinuria, who had blood pressure (BP) < 160/100 mmHg, with no change in their blood pressure (BP) medications 1 month prior to enrollment. Controls were aged 30-80 years, with an eGFR ≥ 60 mL/min/1.73m2, no proteinuria, and baseline blood pressure (BP) values < 160/100 mmHg. We excluded pregnant or breastfeeding women, patients on any insulin sensitizer or medication for treatment of metabolic syndrome, patients with decompensated heart failure or those who had an acute CVD event in the last 6 months. We also excluded patients who had received systemic glucocorticoids or immunomodulators within one month of enrollment in the study or had active or severe inflammatory diseases. The study was approved by the VUMC and VA institutional review boards and informed consent was obtained from all participants. Study Protocol Hyperinsulinemic Euglycemic Clamp Whole-body glucose disposal was evaluated using a glucose clamp after an eight-hour overnight fast as originally described by DeFronzo14. Blood was drawn, and two peripheral IV’s were placed in both upper extremities. In order to suppress hepatic gluconeogenesis and augment skeletal and adipose glucose uptake, human regular insulin (50 units/ 50 mL of 0.9% saline) was infused at a rate of 80mU/m2/min for CKD patients and 40mU/m2/min for control participants. Additionally, 20% dextrose and potassium phosphate were infused to maintain blood glucose concentrations between 90 – 105 mg/dL and prevent insulin induced hypokalemia. Glucose was checked every five minutes. Steady-state was achieved when blood glucose readings remained stable (less than 10% variation between readings) for over 30 minutes and there were no changes to the glucose infusion rate. In steady-state conditions, the amount of glucose infused is equal to the amount of glucose taken up by the tissue or “M”. The M-value was normalized to body weight and used to calculate the Insulin Sensitivity Index (ISI). Blood was collected at regular intervals during the clamp procedure. Predictors and covariates The main predictors for this study were peripheral and hepatic insulin sensitivity calculated using clamp-derived ISI and HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) respectively. Insulin sensitivity index was calculated as: M/(G x ΔI) 15, where M is the glucose disposal rate in mg/kg/min = (dextrose infusion rate at steady state in mL/hour x 184) / (weight in kg) x 60); G = mean steady state glucose concentration in mg/dL; and ΔI is the difference in plasma insulin concentrations at the beginning and the end of the steady state period measured in µU/mL. HOMA-IR was calculated as: Fasting serum insulin (µU/mL) x Fasting serum glucose (mg/dL)/405. 16-19 Covariates included demographics (age and sex), eGFR, BMI [weight (Kg)/height (m) 2], inflammatory markers (hsCRP and IL6), serum osmolality, adiponectin, and leptin. eGFR was calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation 20 . Participants were classified as being obese based on the WHO classification (BMI ≥ 30 kg/m2) and CKD was defined as eGFR < 60mL/min/1.73m2. Serum osmolality was calculated as follows: Serum Osm = (Na+ x 2) + (Urea/2.8) +(Glucose/18).21 Values for Na+ (mEq/L), Glucose (mg/dL), and BUN (md/dL) were
Load more

Recommended publications
  • Copeptin Adds Prognostic Information After Ischemic Stroke: Results from the Corisk Study
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2013 Copeptin adds prognostic information after ischemic stroke: results from the CoRisk study De Marchis, Gian Marco ; Katan, Mira ; Weck, Anja ; Fluri, Felix ; Foerch, Christian ; Findling, Oliver ; Schuetz, Philipp ; Buhl, Daniela ; El-Koussy, Marwan ; Gensicke, Henrik ; Seiler, Marlen ; Morgenthaler, Nils ; Mattle, Heinrich P ; Mueller, Beat ; Christ-Crain, Mirjam ; Arnold, Marcel Abstract: OBJECTIVE: To evaluate and validate the incremental value of copeptin in the prediction of outcome and complications as compared with established clinical variables. METHODS: In this prospec- tive, multicenter, cohort study, we measured copeptin in the emergency room within 24 hours from symptom onset in 783 patients with acute ischemic stroke. The 2 primary end points were unfavor- able functional outcome (modified Rankin Scale score 3-6) and mortality within 90 days. Secondary end points were any of 5 prespecified complications during hospitalization. RESULTS: In multivariate analysis, higher copeptin independently predicted unfavorable outcome (adjusted odds ratio 2.17 for any 10-fold copeptin increase [95% confidence interval CI, 1.46-3.22], p < 0.001), mortality (adjusted hazard ratio 2.40 for any 10-fold copeptin increase [95% CI, 1.60-3.60], p < 0.001), and complications (adjusted odds ratio 1.93 for any 10-fold copeptin increase [95% CI, 1.33-2.80], p = 0.001). The discriminatory ac- curacy, calculated with the area under the receiver operating characteristic curve, improved significantly for all end points when adding copeptin to the NIH Stroke Scale score and the multivariate models.
    [Show full text]
  • Copeptin and Its Potential Role in Diagnosis and Prognosis of Various Diseases Lidija Dobša*1, Kido Cullen Edozien2
    Review Copeptin and its potential role in diagnosis and prognosis of various diseases Lidija Dobša*1, Kido Cullen Edozien2 1Health Institution Varaždin County, Medical Biochemistry Laboratory, Varaždin, Croatia 2Mater Dei Hospital, Msida, Malta *Corresponding author: [email protected] Abstract The need for faster diagnosis, more accurate prognostic assessment and treatment decisions in various diseases has lead to the investigations of new biomarkers. The hope is that this new biomarkers will enable early decision making in clinical practice. Arginine vasopressin (AVP) is one of the main hormones of the hypothalamic-pituitary-adrenal axis. Its main stimulus for secretion is hyperosmolarity, but AVP system is also stimulated by ex- posure of the body to endogenous stress. Reliable measurement of AVP concentration is diffi cult because it is subject to preanalytical and analytical errors. It is therefore not used in clinical practice. Copeptin, a 39-aminoacid glycopeptide, is a C-terminal part of the precursor pre-provasopressin (pre-proAVP). Activation of AVP system stimulates copeptin secretion into the circulation from the posterior pituitary gland in equimolar amounts with AVP. Therefore, copeptin directly refl ects AVP concentration and can be used as surrogate biomarker of AVP secretion. Even mild to moderate stress situations contribute to release of copeptin. These reasons have lead to a handful of research on copeptin in various diseases. This review sum- marizes the current achievements in the research of copeptin as a diagnostic and prognostic marker and also discusses its association in diff erent disease processes. Key words: human copeptin; endogenous stress; diagnostic accuracy; prognosis Received: November 29, 2012 Accepted: May 01, 2013 Introduction Copeptin, a 39-aminoacid glycopeptide is a C-ter- any signifi cant function in the circulation (6).
    [Show full text]
  • COPEPTIN in EARLY DIAGNOSIS of MYOCARDIAL INFARCTION in PATIENTS with ACUTE CORONARY SYNDROME NABIEV DASTAN ERGALIULY Astana Medical University
    Extended Abstract Journal of Cognitive Neuropsychology 2021 Vol.5 No.1 COPEPTIN IN EARLY DIAGNOSIS OF MYOCARDIAL INFARCTION IN PATIENTS WITH ACUTE CORONARY SYNDROME NABIEV DASTAN ERGALIULY Astana Medical University Introduction: Emergency care for patients with suspected myocardial Copeptin levels can be used as a diagnostic marker in patients infarction is critically important in the fight for the patient's life, with suspected MI in combination with other biomarkers, but, in our study we want to present a new opportunity for early to date, the potential significance of copeptin in the early diagnosis of myocardial infarction, which will allow faster diagnosis of MI remains insufficiently understood, which verification of the diagnosis. Among patients with acute necessitates further research. Copeptin, a glycopeptide acid coronary syndrome, it is important to identify groups of patients consisting of 39 amino acids, is the C-terminal part of with myocardial necrosis who have an increased risk of proasopressin and is excreted together with AVP in equimolar complications and death. In this group of patients, the most concentrations, reflecting the level of endogenous stress in the aggressive treatment tactics are indicated, including the use of human body. Direct determination of vasopressin content is percutaneous coronary intervention or coronary artery bypass difficult today, since the hormone in the blood is unstable, has a grafting. Currently, the "gold standard" in verifying myocardial short half-life, and 90% of the circulating hormone is associated necrosis and, consequently, infarction is the determination of an with platelets [8]. Therefore, an accurate, reproducible and increase in the level of troponin T or I.
    [Show full text]
  • Prognostic and Diagnostic Significance of Copeptin in Acute Exacerbation
    Winther et al. Respiratory Research (2017) 18:184 DOI 10.1186/s12931-017-0665-z RESEARCH Open Access Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study Jacob A. Winther1,2*, Jon Brynildsen1,2, Arne Didrik Høiseth1,2, Heidi Strand4, Ivar Følling1,2, Geir Christensen3, Ståle Nygård5, Helge Røsjø1,2 and Torbjørn Omland1,2 Abstract Background: Copeptin is a novel biomarker that predicts mortality in lower respiratory tract infections and heart failure (HF), but the diagnostic value of copeptin in acute dyspnea and the prognostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not clear. Method: We determined copeptin and NT-proBNP concentrations at hospital admission in 314 patients with acute dyspnea who were categorized by diagnosis. Survival was registered after a median follow-up of 816 days, and the prognostic and diagnostic properties of copeptin and NT-proBNP were analyzed in acute HF (n = 143) and AECOPD (n = 84) separately. Results: The median concentration of copeptin at admission was lower in AECOPD compared to acute HF (8.8 [5. 2–19.7] vs. 22.2 [10.2–47.9]) pmol/L, p < 0.001), but NT-proBNP discriminated acute HF from non-HF related dyspnea more accurately than copeptin (ROC-AUC 0.85 [0.81–0.89] vs. 0.71 [0.66–0.77], p < 0.0001). Adjusted for basic risk factors, increased copeptin concentrations predicted mortality in AECOPD (HR per log (ln) unit 1.72 [95% CI 1.21–2.
    [Show full text]
  • Copeptin Helps in the Early Detection of Patients with Acute Myocardial
    Journal of the American College of Cardiology Vol. 62, No. 2, 2013 Ó 2013 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2013.04.011 Biomarkers Copeptin Helps in the Early Detection of Patients With Acute Myocardial Infarction Primary Results of the CHOPIN Trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction) Alan Maisel, MD,* Christian Mueller, MD, Sean-Xavier Neath, MD, PHD, y z y Robert H. Christenson, PHD, Nils G. Morgenthaler, MD, PHD, James McCord, MD, x k { Richard M. Nowak, MD, Gary Vilke, MD, Lori B. Daniels, MD, MAS, Judd E. Hollander, MD,# { y y Fred S. Apple, PHD,** Chad Cannon, MD, John T. Nagurney, MD, Donald Schreiber, MD, yy zz xx Christopher deFilippi, MD, Christopher Hogan, MD, Deborah B. Diercks, MD, x kk {{ John C. Stein, MD, MAS,## Gary Headden, MD,*** Alexander T. Limkakeng, JR, MD, MHSC, yyy Inder Anand, MD, DPHIL (OXON), Alan H. B. Wu, PHD,## Jana Papassotiriou, PHD, zzz xxx Oliver Hartmann, MS, Stefan Ebmeyer, MD, Paul Clopton, MS,* Allan S. Jaffe, MD, xxx xxx kkk W. Frank Peacock, MD {{{ San Diego, Sacramento, Palo Alto, and San Francisco, California; Basel, Switzerland; Baltimore, Maryland; Berlin, Germany; Detroit, Michigan; Philadelphia, Pennsylvania; Minneapolis, Minnesota; Kansas City, Kansas; Boston, Massachusetts; Richmond, Virginia; Charleston, South Carolina; Durham, North Carolina; Hennigsdorf/Berlin, Germany; Rochester, Minnesota; and Houston, Texas Objectives The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED).
    [Show full text]
  • Copeptin—Marker of Acute Myocardial Infarction
    Curr Atheroscler Rep (2014) 16:421 DOI 10.1007/s11883-014-0421-5 CARDIOVASCULAR DISEASE AND STROKE (P PERRONE-FILARDI AND S. AGEWALL, SECTION EDITORS) Copeptin—Marker of Acute Myocardial Infarction Martin Möckel & Julia Searle Published online: 21 May 2014 # The Author(s) 2014. This article is published with open access at Springerlink.com Abstract The concentration of copeptin, the C-terminal part Introduction of pro-arginine vasopressin, has been shown to increase early after acute and severe events. Owing to complementary path- Ever since Reichlin et al. [1] published their article entitled ophysiology and kinetics, the unspecific marker copeptin, in “Incremental value of copeptin for rapid rule-out of acute combination with highly cardio-specific troponin, has been myocardial infarction” in 2009, the concept of a single, com- evaluated as an early-rule-out strategy for acute myocardial bined troponin and copeptin test at admission in patients with infarction in patients presenting with signs and symptoms of suspected acute coronary syndrome (ACS) has been tested acute coronary syndrome. Overall, most studies have reported and reported in an increasing number of publications, with a negative predictive value between 97 and 100 % for the conflicting results and conclusions. diagnosis of acute myocardial infarction in low- to Copeptin is the C-terminal part of pro-arginine vasopressin. intermediate-risk patients with suspected acute coronary syn- Vasopressin is an important hormone for water homeostasis, but drome. Additionally, a recent multicenter, randomized process has a very short half-life and is unstable in vitro, which makes its study, where patients who tested negative for copeptin and quantification difficult.
    [Show full text]
  • Copeptin As a Marker of Outcome After Cardiac Arrest
    Düring et al. Critical Care (2020) 24:185 https://doi.org/10.1186/s13054-020-02904-8 RESEARCH Open Access Copeptin as a marker of outcome after cardiac arrest: a sub-study of the TTM trial Joachim Düring1*, Martin Annborn2, Tobias Cronberg3, Josef Dankiewicz4, Yvan Devaux5, Christian Hassager6, Janneke Horn7, Jesper Kjaergaard6, Michael Kuiper8, Homa Rafi Nikoukhah9, Pascal Stammet10, Johan Undén11, Michael Jaeger Wanscher12, Matt Wise13, Hans Friberg1 and Niklas Nielsen2 Abstract Background: Arginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest. Methods: Serial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score. Results: Six hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deteriorationwithin24h,and273(39.6%)diedwithin30days.Copeptinmeasuredat24hwasfoundtobeindependently associated with 30-day survival, hazard ratio 1.17 [1.06–1.28], p = 0.001; circulatory cause of death, odds ratio 1.03 [1.01–1.04], p = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02–1.08], p < 0.001.
    [Show full text]
  • Copeptin Under Glucagon Stimulation
    Endocrine (2016) 52:344–351 DOI 10.1007/s12020-015-0783-7 ORIGINAL ARTICLE Copeptin under glucagon stimulation 1 1 1 Krzysztof C. Lewandowski • Andrzej Lewin´ski • Elzbieta_ Skowron´ska-Jo´z´wiak • 2 3 4,5 Magdalena Stasiak • Wojciech Horzelski • Georg Brabant Received: 8 August 2015 / Accepted: 20 October 2015 / Published online: 17 November 2015 Ó The Author(s) 2015. This article is published with open access at Springerlink.com Abstract Stimulation of growth hormone (GH) and patients with intact pituitary function but not in hypopitu- adrenocorticotropic hormone (ACTH) secretion by gluca- itarism. Copeptin concentrations were stimulated over time gon is a standard procedure to assess pituitary dysfunction and the maximal increment correlated with ACTH, while but the pathomechanism of glucagon action remains correlations between copeptin and GH were weaker. unclear. As arginine vasopressin (AVP) may act on the Interestingly, copeptin as well as GH secretion was sig- release of both, GH and ACTH, we tested here the role of nificantly attenuated when comparing subjects within the AVP in GST by measuring a stable precursor fragment, highest to those in the lowest BMI quartile (p \ 0.05). copeptin, which is stoichiometrically secreted with AVP in Copeptin is significantly released following glucagon a 1:1 ratio. ACTH, cortisol, GH, and copeptin were mea- stimulation. As this release is BMI-dependent, the time- sured at 0, 60, 90, 120, 150, and 180 min during GST in 79 dependent relation between copeptin and GH may be subjects: healthy controls (Group 1, n = 32), subjects with obscured, whereas the close relation to ACTH suggests that pituitary disease, but with adequate cortisol and GH AVP/copeptin release might be linked to the activation of responses during GST (Group 2, n = 29), and those with the adrenal axis.
    [Show full text]
  • Effect of Increased Water Intake on Plasma Copeptin in Healthy Adults
    Eur J Nutr DOI 10.1007/s00394-017-1471-6 ORIGINAL CONTRIBUTION Effect of increased water intake on plasma copeptin in healthy adults Guillaume Lemetais1 · Olle Melander2,3 · Mariacristina Vecchio1 · Jeanne H. Bottin1 · Sofa Enhörning2,4 · Erica T. Perrier1 Received: 5 August 2016 / Accepted: 6 May 2017 © The Author(s) 2017. This article is an open access publication Abstract urine osmolality and urine specifc gravity decreased from Purpose Inter-individual variation in median plasma 591 206 to 364 117 mOsm/kg (p < 0.001) and from ± ± copeptin is associated with incident type 2 diabetes mel- 1.016 0.005 to 1.010 0.004 (p < 0.001), respectively. ± ± litus, progression of chronic kidney disease, and cardio- Conclusions At baseline, circulating levels of copeptin vascular events. In this study, we examined whether 24-h were positively associated with 24-h urine concentration in urine osmolality was associated with plasma copeptin and healthy young subjects with various fuid intakes. Moreo- whether increasing daily water intake could impact circu- ver, this study shows, for the frst time, that increased water lating plasma copeptin. intake over 6 weeks results in an attenuation of circulating Methods This trial was a prospective study conducted at a copeptin. single investigating center. Eighty-two healthy adults (age Clinical Trial Registration Number NCT02044679. 23.6 2.9 years, BMI 22.2 1.5 kg/m2, 50% female) ± ± were stratifed based upon habitual daily fuid intake vol- Keywords Copeptin · Fluid intake · Hydration · Urine umes: arm A (50–80% of EFSA dietary reference values), osmolality · Water intake arm B (81–120%), and arm C (121–200%).
    [Show full text]
  • Copeptin Concentrations During Psychological Stress: the Psyco Study
    J Siegenthaler, C Walti, Copeptin levels and 171:6 737–742 Clinical Study S A Urwyler and others psychological stress Copeptin concentrations during psychological stress: the PsyCo study Judith Siegenthaler*, Carla Walti*, Sandrine Andrea Urwyler,*, Philipp Schuetz1 and Mirjam Christ-Crain† Correspondence Clinic of Endocrinology, Diabetology, and Metabolism, University Hospital Basel, Petersgraben 4, Basel CH-4031, should be addressed Switzerland and 1Department of Internal Medicine, Kantonsspital Aarau, Tellstrasse, Aaraun CH-5001, Switzerland to M Christ-Crain *(J Siegenthaler, C Walti and S A Urwyler contributed equally to this work) Email †M Christ-Crain is now at Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, mirjam.christ- Petersgraben 4, CH-4031 Basel, Switzerland [email protected] Abstract Objective: The prognostic/diagnostic biomarker copeptin, an arginine vasopressin surrogate, reflects physical stress. Whether copeptin concentration increases upon psychological stress is unknown. We investigated psychological stress effects on copeptin secretion in healthy volunteers and patients with central diabetes insipidus (DI). Design: A prospective observational study was conducted to study the relation between copeptin concentration and psychological stress. Methods: A total of 20 healthy adults (ten female) and eight patients with central DI (four female) underwent the Trier Social Stress Test including, in order, 30-min waiting period, 10-min anticipation period, 10-min test period and 40-min recovery. Serum copeptin and cortisol concentrations and self-rated stress component feelings were determined in the pre-/post- anticipation period, post-test period and twice post-recovery. Results: In healthy volunteers, the median (25th–75th percentile) copeptin concentration peaked immediately during the post-test period at 5.1 (3.2–7.0) pmol/l, vs 3.7 (2.6–5.4) pmol/l at baseline.
    [Show full text]
  • Predictive Value of Plasma Copeptin Level for Diagnosis and Mortality of Pulmonary Embolism
    ORIGINAL ARTICLE Predictive value of plasma copeptin level for diagnosis and mortality of pulmonary embolism Caglar Ozmen1 Onur Sinan Deveci1 Muhammet Bugra Karaaslan2 Oya Baydar3 Anil Akray1 Ali Deniz1 Caglar Emre Cagliyan1 Ismail Hanta3 Ayhan Usal1 1. Cukurova University, Faculty of Medicine, Department of Cardiology, Adana, Turkey. 2. Osmancik State Hospital, Department of Cardiology, Osmancık/Çorum, Turkey. 3. Cukurova University Faculty of Medicine, Department of Chest Disease, Adana, Turkey. http://dx.doi.org/10.1590/1806-9282.66.12.1645 SUMMARY OBJECTIVE: Early diagnosis and risk stratification may provide a better prognosis in pulmonary embolism (PE). Copeptin has emerged as a valuable predictive biomarker in various cardiovascular diseases. The aim of this study was to determine the levels of copeptin in patients with acute PE and to evaluate its relationship with disease severity and PE-related death. METHODS: Fifty-four patients and 60 healthy individuals were included in this study. Copeptin concentrations and right ventricular dys- function were analyzed. The correlation between copeptin levels and hemodynamic and echocardiographic parameters was examined. After these first measurements, patients were evaluated with PE-related mortality at the one-year follow-up. RESULTS: The copeptin levels were higher in PE patients than in the control group (8.3 ng/mL vs 3.8 ng/mL, p<0.001). Copeptin levels were found to be significantly higher in patients with PE-related death and right ventricular dysfunction (10.2 vs 7.5 ng/ml, p=0.001; 10.5 vs 7.5 ng/ml, p=0.002, respectively). When the cut-off value of copeptin was ≥5.85, its sensitivity and specificity for predicting PE were 71.9% and 85.0%, respectively (AUC=0.762, 95% CI=0.635-0.889, p<0.001).
    [Show full text]
  • Plasma Copeptin and Risk of Lower-Extremity Amputation In
    2290 Diabetes Care Volume 42, December 2019 Plasma Copeptin and Risk of Louis Potier,1,2,3 Ronan Roussel,1,2,3 Michel Marre,1,2,3,4 Petter Bjornstad,4 Lower-Extremity Amputation in David Z. Cherney,5 Ray El Boustany,1,3 Fred´ eric´ Fumeron,2,3 Nicolas Venteclef,3 Type 1 and Type 2 Diabetes Jean-François Gautier,2,3,6 Samy Hadjadj,7 Kamel Mohammedi,8,9,10 and 3 Diabetes Care 2019;42:2290–2297 | https://doi.org/10.2337/dc19-1062 Gilberto Velho OBJECTIVE Diabetes is the leading cause of nontraumatic lower-extremity amputations (LEAs). Identification of patients with foot ulcers at risk for amputation remains clinically challenging. Plasma copeptin, a surrogate marker of vasopressin, is associated with the risk of cardiovascular and renal complications in diabetes. RESEARCH DESIGN AND METHODS We assessed the association between baseline plasma copeptin and risk of LEA 1Department of Diabetology, Endocrinology and during follow-up in four cohorts of people with type 1 (GENESIS, n 5 503, and Nutrition, DHU FIRE, Bichat Hospital, Assistance GENEDIAB, n 5 207) or type 2 diabetes (DIABHYCAR, n 5 3,101, and SURDIAGENE, Publique – Hopitauxˆ de Paris, Paris, France 2 n 5 1,452) with a median duration of follow-up between 5 and 10 years. Copeptin Universite´ de Paris, Paris, France 3INSERM, UMRS 1138, Cordeliers Research Cen- concentration was measured in baseline plasma samples by an immunolumino- ter, Paris, France metric assay. 4Section of Endocrinology, Department of Pedi- atrics,and DivisionofNephrology,Departmentof RESULTS Medicine, University of Colorado School of Med- Inthepooledcohorts with type1diabetes(n5 710),thecumulativeincidenceof LEA icine, Aurora, CO 5Division of Nephrology, Department of Medi- during follow-up by increasing tertiles (tertile 1 [TER1], TER2, and TER3) of baseline cine, Toronto General Hospital, University of plasma copeptin was 3.9% (TER1), 3.3% (TER2), and 10.0% (TER3) (P 5 0.002).
    [Show full text]