The influence of sampling time on indirect reference limits, decision limits, and the estimation of biological variation of random plasma glucose concentrations

Abstract Objectives Plasma glucose concentrations exhibit a pronounced daytime-dependent variation. The oscillations responsible for this are currently not considered in the determination of reference limits (RL) and decision limits. Methods We characterized the daily variation inherent in large-scale laboratory data from two different university hospitals (site 1 n=513,682, site 2 n=204,001). Continuous and distinct RL for daytime and night were estimated. Diurnal characteristics of glucose concentrations were further investigated by quantile regression analyses introducing age and cosinor-functions as predictors in the model. Results Diurnal variations expressed as amplitude/Midline Estimating Statistic of Rhythm (MESOR) ratio, averaged 7.7% (range 5.9–9.3%). The amplitude of glucose levels decreased with increasing concentrations. Between 06:00 and 10:00 h an average decrease of 4% has to be considered. Nocturnal glucose samples accounted for only 5% of the total amount but contributed to 19.5% of all findings over 11.1 mmol/L. Partitioning of RL between day and night is merely justified for the upper reference limit. The nocturnal upper RLs for both genders differed from those obtained during the day by 11.0 and 10.6% at site 1 and by 7.6 and 7.5% at site 2. Conclusions We conclude that indirect approaches to estimate upper RL of random plasma glucose concentrations require stratification concerning the time of sample collection.

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Factors Enhancing Serum Syndecan-1 Concentrations: A Large-Scale Comprehensive Medical Examination

Journal of Clinical Medicine ◽

10.3390/jcm8091320 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1320

Author(s):

Kazumasa Oda ◽

Hideshi Okada ◽

Akio Suzuki ◽

Hiroyuki Tomita ◽

Ryo Kobayashi ◽

...

Keyword(s):

Large Scale ◽

Prospective Observational Study ◽

Nitrogen Concentration ◽

Laboratory Data ◽

University Hospital ◽

Endothelial Glycocalyx ◽

Sample Collection ◽

Blood Samples ◽

Triglyceride Concentration ◽

Medical Examinations

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.

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Glucose Intolerance as Morbidity in Schizophrenia

European Psychiatry ◽

10.1016/s0924-9338(09)71431-2 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

V. Sibinovic ◽

S. Raicevic-Sibinovic ◽

V. Slavkovic

Keyword(s):

Diabetes Mellitus ◽

Glucose Intolerance ◽

Plasma Glucose ◽

Laboratory Data ◽

Elevated Serum ◽

Antipsychotic Therapy ◽

Family History Of Diabetes ◽

Glucose Levels ◽

Onset Diabetes ◽

New Onset

This was an eight months prospective study.Study was active controlled in patients who were hospitalized in our Clinic. Schizophrenia was diagnosed by using PANSS scale and by using MKB 10 criteria. Laboratory data were measured at baseline, every month after therapy and at endpoint. Laboratory tests included glucose level in serum and OGTT, which were determined from blood, before breakfast and in the same hospital laboratory. Patients with family history of diabetes mellitus were excluded from the study.A total of 30 patients were recruited. the risperidone shows clinically insignificant effect on plasma glucose levels. Incidence of new onset diabetes was abaut 5% higher with olanzapine than risperidone, and the biggest increasing was in first three months. Elevated serum glucose levels have been shown with clozapine and dose-related effects were noted. We also found modest, but significant risk for increasing plasma glucose levels in patients with chlorpromazine medication. Lack of relationship between serum levels of zuclopentixol and plasma glucose has been shown. There are no apparent problems with sulpiride and with haloperidol. Medication with chlorpromazine did not show any significant modifications to blood glucose levels.The antipsychotics appear to be associated with the development of glucose intolerance, new-onset diabetes mellitus and exacerbation of existing diabetes mellitus. These disturbances in glucose metabolism have their own medical consequences. Thus, to minimize morbidity and mortality associated with the use of antipsychotic medications, close screening and monitoring for diabetes mellitus should become a priority for all clinicians treating schizophrenia patients receiving antipsychotic therapy.

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Diagnostic accuracy of free and total metanephrines in plasma and fractionated metanephrines in urine of patients with pheochromocytoma

Acta Endocrinologica ◽

10.1530/eje-09-0996 ◽

2010 ◽

Vol 162 (5) ◽

pp. 951-960 ◽

Cited By ~ 63

Author(s):

Eric Grouzmann ◽

Laurence Drouard-Troalen ◽

Eric Baudin ◽

Pierre-François Plouin ◽

Beat Muller ◽

...

Keyword(s):

Renal Insufficiency ◽

Case Control ◽

University Hospitals ◽

Retrospective Case ◽

Reference Limit ◽

Test Study ◽

Confirmation Test ◽

Upper Reference Limit ◽

Urinary Metanephrines

BackgroundPlasma free and urinary metanephrines are recognized biomarkers for the assessment of pheochromocytoma. Plasma total metanephrines with a long half-life may represent another useful biomarker.ObjectiveThe aim of this study is to evaluate the diagnostic performances of plasma total metanephrines alone or combined with free metanephrines and fractionated 24-h urinary metanephrines.MethodsA retrospective, case–control diagnostic test study was conducted between 1999 and 2007 in two university hospitals in Switzerland and two institutions in France. The patients included 46 cases with histologically proven pheochromocytoma, and 181 controls suspected of tumor with negative investigations and 3-year follow-up. None had renal dysfunction. Sensitivity and specificity were compared after expressing each measurement result as a ratio over its upper reference limit, adding the ratios of normetanephrine and metanephrine, and defining cut-off values of 1 or 2 for this sum.ResultsApplying a cut-off value of 1, plasma free and total metanephrines and urinary fractionated metanephrines had similar sensitivities of 96% (95% confidence interval, 86–99%), 95% (85–99%), and 95% (84–99%) along with similar specificities of 89% (83–94%), 91% (84–95%), and 86% (80–91%). A cut-off of 2 for the sum of ratios over reference limit improves the specificity, and it can be used for a confirmation test based on another biomarker taken among the three biomarkers.ConclusionAll three metanephrine-based tests perform equivalently for diagnosing pheochromocytoma in the absence of renal insufficiency, and can be conveniently associated two by two for confirming/excluding tumor.

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Evaluation of plasma N-terminal pro-B-type natriuretic peptide levels in healthy North American Salukis with normal echocardiographic measurements.

10.1101/2021.11.03.467139 ◽

2021 ◽

Author(s):

Tamilselvam Gunasekaran ◽

Christopher Brennan ◽

Robert Sanders

Keyword(s):

Body Weight ◽

Heart Disease ◽

Natriuretic Peptide ◽

Plasma Concentrations ◽

Clinical Use ◽

Reference Limit ◽

Cardiac Health ◽

Percentile Method ◽

Reference Limits ◽

Upper Reference Limit

Measurement of N‐terminal pro‐B‐type natriuretic peptide (NT-proBNP) levels has been shown to have clinical significance for diagnosis and management of heart disease in dogs. Evaluation of current reference limits for specific breeds is necessary to ensure the test can accurately distinguish between healthy and diseased animals. The objective of this study is to evaluate the adequacy of currently established NT-proBNP reference limits for clinical use in healthy Salukis. Cardiac health of 33 clinically healthy Salukis was evaluated via echocardiography using available breed standards. Plasma concentrations of NT-proBNP were measured using a commercially available assay. A one-sided 97.5% upper reference limit for the NT-proBNP concentrations was calculated using non-parametric percentile method. The 97.5% upper reference limit was 769 pmol/L (90% CI, 547-1214 pmol/L) for the study dogs. This upper reference limit was within the currently established non-breed specific NT-proBNP upper reference limit of 900 pmol/L. No relationship between sex, age, or body weight on plasma levels of NT-proBNP was noted. Results of this study supports the use of currently available non-breed specific NT-proBNP cut-off values for clinical evaluation of healthy Salukis.

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Prolonged Survival in an Aged Labrador Retriever with a Metastatic Insulinoma

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-5860 ◽

2013 ◽

Vol 49 (3) ◽

pp. 224-229 ◽

Cited By ~ 1

Author(s):

Jessica Rychel ◽

Deanna R. Worley ◽

Christine S. Hardy ◽

Brett T. Webb

Keyword(s):

Serum Insulin ◽

Pancreatic Insufficiency ◽

Exocrine Pancreatic Insufficiency ◽

Labrador Retriever ◽

Hypoglycemic Episode ◽

Partial Pancreatectomy ◽

Reference Limit ◽

Glucose Levels ◽

Initial Surgery ◽

Upper Reference Limit

This case report highlights an unusually prolonged, asymptomatic, disease-free interval in an aged male Labrador retriever that underwent partial pancreatectomy for a functionally active pancreatic insulinoma with histologically confirmed hepatic metastasis. The patient developed pancreatitis and nonseptic suppurative peritonitis 24 hr after surgical resection of the insulinoma and was managed medically until discharge. Three mo after surgery, the dog was diagnosed with exocrine pancreatic insufficiency (EPI) that was effectively managed with parenteral pancreatic enzymes. Due to normal glucose levels 3 mo postsurgically, liver samples from the initial surgery were resubmitted for immunohistochemistry. Results confirmed insulinoma metastasis with insulin expression. Ten mo postsurgically, the blood glucose was normal and serum insulin levels were slightly above the upper reference limit. The first hypoglycemic episode was documented 23 mo postoperatively, which was effectively managed with prednisone. The cause for the prolonged disease remission and survival was unknown, but was possibly a result of pancreatitis and peritonitis, partial spontaneous regression of metastatic lesions, or idiopathic. Despite life-threatening postoperative complications, this patient enjoyed a profoundly longer than expected survival. This case highlights the importance of removing the primary tumor (insulinoma) despite the presence of metastatic disease.

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Establishing consensus-based, assay-specific 99th percentile upper reference limits to facilitate proper utilization of cardiac troponin measurements

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0067 ◽

2017 ◽

Vol 55 (11) ◽

Cited By ~ 6

Author(s):

Dina N. Greene ◽

Jillian R. Tate

Keyword(s):

Sample Size ◽

Cardiac Troponin ◽

Medical Decision ◽

Decision Point ◽

Consensus Approach ◽

Exclusion Criteria ◽

Reference Limit ◽

Population Selection ◽

Reference Limits ◽

Upper Reference Limit

AbstractImplementation of the 99th percentile as the upper reference limit for cardiac troponin (cTn) assays is a seemingly lucid recommendation, but, in reality, is incredibly complex. Lack of harmonization between cTn assays diminishes the ability to have a single medical decision point across manufacturer assay/instruments. Moreover, even within a single cTn assay there are several published values corresponding to the “99th percentile”. Variability in the determined value is primarily a function of population selection including: sample size, age, sex, exclusion criteria, and statistical methods. Given the complexities associated with this value, some countries have taken an expert consensus approach to endorsing harmonized, assay-specific, cTn 99th percentile values. The purpose of this manuscript is to highlight the intricacies associated with selecting a cTn 99th percentile and to review the approach that Australia used to endorse a nationwide upper reference limit for the Architect STAT hs-cTnI assay.

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Factors Enhancing Serum Syndecan-1 Concentrations: A Large-Scale Comprehensive Medical Examination

10.20944/preprints201906.0291.v1 ◽

2019 ◽

Author(s):

Kazumasa Oda ◽

Hideshi Okada ◽

Akio Suzuki ◽

Hiroyuki Tomita ◽

Ryo Kabayashi ◽

...

Keyword(s):

Large Scale ◽

Prospective Observational Study ◽

Nitrogen Concentration ◽

Laboratory Data ◽

University Hospital ◽

Endothelial Glycocalyx ◽

Sample Collection ◽

Blood Samples ◽

Triglyceride Concentration ◽

Medical Examinations

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018, to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.

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Calculation of indirect reference intervals of plasma lipase activity of adults from existing laboratory data based on the Reference Limit Estimator integrated in the OPUS::L information system

Journal of Laboratory Medicine ◽

10.1515/labmed-2021-0008 ◽

2021 ◽

Vol 45 (2) ◽

pp. 131-134

Author(s):

Britta Amodeo ◽

Aline Schindler ◽

Ulrike Schacht ◽

Hans Günther Wahl

Keyword(s):

Information System ◽

Lipase Activity ◽

Clinical Chemistry ◽

Laboratory Data ◽

Direct Methods ◽

Reference Interval ◽

Reference Intervals ◽

Specific Reference ◽

Reference Limit ◽

Reference Limits

Abstract Objectives Most laboratories have difficulties to determine their own reference intervals for the diagnostic evaluation of patient results by direct methods. Therefore, data is often just taken from the literature or package inserts of the analytical tests. Methods The section on Reference Limits of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) first uploaded the Reference Limit Estimator (RLE) as an R-program with MS Excel-interface on the DGKL home page and now this tool is implemented in the commercial Laboratory Information System OPUS::L (OSM AG Essen, Germany). We used this OPUS::L “Population specific Reference Limits” tool online with our laboratory database. First calculations were done using the example of lipase. Results The manufacturer’s original reference interval for lipase 12–53 U/L (adults) was changed to age dependent upper reference limits of <41 U/L (<20 years), <60 U/L (20–80 years) and <70 U/L (>80 years). Conclusions By means of the OPUS::L “Population specific Reference Limits” tool we were able to establish our laborarotry specific reference interval for plasma lipase activity. The new reference limits helped to solve an old problem of implausible low elevated lipase values.

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