Publications by authors named "Randie R Little"

67 Publications

Continuous Glucose Monitoring and Use of Alternative Markers To Assess Glycemia in Chronic Kidney Disease.

Diabetes Care 2020 10 11;43(10):2379-2387. Epub 2020 Aug 11.

Kidney Research Institute, University of Washington, Seattle, WA.

Objective: In chronic kidney disease, glycated albumin and fructosamine have been postulated to be better biomarkers of glycemic control than HbA. We evaluated the accuracy, variability, and covariate bias of three biomarkers (HbA, glycated albumin, and fructosamine) compared with continuous glucose monitoring (CGM)-derived measurement of glycemia across estimated glomerular filtration rate (eGFR) in type 2 diabetes.

Research Design And Methods: A prospective cohort study was conducted of 104 participants with type 2 diabetes, 80 with eGFR <60 mL/min/1.73 m (not treated with dialysis) and 24 frequency-matched control subjects with eGFR ≥60 mL/min/1.73 m. Participants wore a blinded CGM for two 6-day periods separated by 2 weeks, with blood and urine collected at the end of each CGM period. HbA, glycated albumin, and fructosamine were measured by high-performance liquid chromatographic, enzymatic, and colorimetric nitroblue tetrazolium methods, respectively.

Results: Within-person biomarker values were strongly correlated between the two CGM periods ( = 0.92-0.95), although no marker fully captured the within-person variability of mean CGM glucose. All markers were similarly correlated with mean CGM glucose ( = 0.71-77). Compared with mean CGM glucose, glycated albumin and fructosamine were significantly biased by age, BMI, serum iron concentration, transferrin saturation, and albuminuria; HbA was underestimated in those with albuminuria.

Conclusions: Glycated albumin and fructosamine were not less variable than HbA at a given mean CGM glucose level, with several additional sources of bias. These results support measuring HbA to monitor trends in glycemia among patients with eGFR <60 mL/min/1.73 m. Direct measurements of glucose are necessary to capture short-term variability.
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http://dx.doi.org/10.2337/dc20-0915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510019PMC
October 2020

Accuracy and Precision of a Point-of-Care HbA1c Test.

J Diabetes Sci Technol 2020 09 10;14(5):883-889. Epub 2019 Mar 10.

Abbott Rapid Diagnostics, a division of Abbott Laboratories, San Diego, CA, USA.

Background: Point-of-care (POC) hemoglobin A1c (HbA1c) testing has advantages over laboratory testing, but some questions have remained regarding the accuracy and precision of these methods. The accuracy and the precision of the POC Afinion™ HbA1c Dx test were investigated.

Methods: Samples spanning the assay range were collected from prospectively enrolled subjects at three clinical sites. The accuracy of the POC test using fingerstick and venous whole blood samples was estimated via correlation and bias with respect to values obtained by an NGSP secondary reference laboratory (SRL). The precision of the POC test using fingerstick samples was estimated from duplicate results by calculating the coefficient of variation (CV) and standard deviation (SD), and separated into its components using analysis of variance (ANOVA). The precision of the POC test using venous blood was evaluated from samples run in four replicates on each of three test cartridge lots, twice per day for 10 consecutive days. The SD and CV by study site and overall were calculated.

Results: Across the assay range, POC test results from fingerstick and venous whole blood samples were highly correlated with results from the NGSP SRL ( = .99). The mean bias was -0.021% HbA1c (-0.346% relative) using fingerstick samples and -0.005% HbA1c (-0.093% relative) using venous samples. Imprecision ranged from 0.62% to 1.93% CV for fingerstick samples and 1.11% to 1.69% CV for venous samples.

Conclusions: The results indicate that the POC test evaluated here is accurate and precise using both fingerstick and venous whole blood.
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http://dx.doi.org/10.1177/1932296819831292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753859PMC
September 2020

The National Glycohemoglobin Standardization Program: Over 20 Years of Improving Hemoglobin A Measurement.

Clin Chem 2019 07 5;65(7):839-848. Epub 2018 Dec 5.

Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD.

Background: Measurement of hemoglobin A1c (HbA) in the blood is integral to and essential for the treatment of patients with diabetes mellitus. HbA reflects the mean blood glucose concentration over the preceding 8 to 12 weeks. Although the clinical value of HbA was initially limited by large differences in results among various methods, the investment of considerable effort to implement standardization has brought about a marked improvement in analysis.

Content: The focus of this review is on the substantial progress that has been achieved in enhancing the accuracy and, therefore, the clinical value of HbA assays.

Summary: The interactions between the National Glycohemoglobin Standardization Program and manufacturers of HbA methods have been instrumental in standardizing HbA. Proficiency testing using whole blood has allowed accuracy-based assessment of methods in individual clinical laboratories that has made an important contribution to improving the HbA measurement in patient samples. These initiatives, supported by the efforts of the IFCC network, have led to a continuing enhancement of HbA methods.Many of the factors that previously influenced HbA results independently of blood glucose have been eliminated from most modern methods. These include carbamylation, labile intermediates, and common hemoglobin variants. Nevertheless, some factors (e.g., race and aging) may alter HbA interpretation, but whether these differences have clinical implications remains contentious. HbA has a fundamental role in the diagnosis and management of diabetes. Ongoing improvements in HbA measurement and quality will further enhance the clinical value of this analyte.
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http://dx.doi.org/10.1373/clinchem.2018.296962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693326PMC
July 2019

Multicenter assessment of a hemoglobin A1c point-of-care device for diagnosis of diabetes mellitus.

Clin Biochem 2018 Nov 17;61:18-22. Epub 2018 Sep 17.

InSource Diagnostics, Monrovia, CA, United States.

Objective: A multisite investigation compared the analytical performance of a point-of-care (POC) HbA1c device with multiple commonly used HbA1c laboratory methods and an NGSP (National Glycohemoglobin Standardization Program) reference method.

Research Design And Methods: The Afinion AS100 POC device analyzed HbA1c using 618 EDTA whole blood excess patient specimens with clinically indicated HbA1c testing. Results were compared to measurements across five clinical laboratories and the NGSP reference method. Precision was evaluated over 8-10 consecutive days for low-, mid-, and high-range HbA1c specimens at all five sites.

Results: Over a wide range of HbA1c values (4.0%-15% HbA1c), 97.1% of the POC results and 94.5% of routine laboratory results fell within the target value of ±6% of the NGSP reference method results. The POC HbA1c results at 6.5% exhibited a total relative bias of -0.6% (-0.04% HbA1c) compared to the reference method while the aggregate of laboratory methods displayed a relative bias of -0.9% (-0.06% HbA1c). The total imprecision of the POC results ranged from 0.74-2.13% CV across the analytic measurement range compared to 0.81-3.23% CV for the routine laboratory methods.

Conclusions: The accuracy and precision of the Afinion POC HbA1c method was comparable to the laboratory HbA1c methods supporting the FDA's recent approval of the Afinion HbA1c Dx device for use in the diagnosis of diabetes.
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http://dx.doi.org/10.1016/j.clinbiochem.2018.09.007DOI Listing
November 2018

Recognition of rare hemoglobin variants by hemoglobin A measurement procedures.

Clin Chim Acta 2018 Jan 14;476:67-74. Epub 2017 Nov 14.

Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, United States. Electronic address:

Background: Unrecognized hemoglobinopathies can lead to measured hemoglobin A (Hb A) concentrations that are erroneous or misleading. We determined the effects of rare hemoglobin variants on capillary electrophoresis (CE) and HPLC methods for measurement of Hb A.

Methods: We prospectively investigated samples in which Hb A was measured by CE during a 14-month period. For samples in which the electropherograms suggested the presence of rare hemoglobinopathies, hemoglobin variants were identified by molecular analysis or by comparison with electropherograms of known variants. When sample volume permitted, Hb A was measured by 2 HPLC measurement procedures and by boronate affinity HPLC.

Results: Hb A was measured by CE in 33,859 samples from 26,850 patients. 15 patients (0.06%) were identified as having rare hemoglobinopathies: Hbs A2 prime, Agenogi, Fannin-Lubbock I, G Philadelphia, G San Jose, J Baltimore, La Desirade, N Baltimore, Nouakchott, and Roanne. Among 6 of these samples tested by 2 ion-exchange HPLC methods, the rare Hb was detected by both HPLC methods in only one sample, and none were detected by boronate affinity HPLC. The mean of the Hb A results of 2 HPLC methods differed from the result of the CE method by 0.7-2.2% Hb A in samples with variant hemoglobins versus <0.2% Hb A1c in samples without variants.

Conclusion: Measurement procedures differ in the ability to detect the presence of rare Hb variants and to quantify Hb A in patients who harbor such variants.
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http://dx.doi.org/10.1016/j.cca.2017.11.012DOI Listing
January 2018

Implementing a Reference Measurement System for C-Peptide: An Addendum.

Clin Chem 2017 12 4;63(12):1904-1905. Epub 2017 Oct 4.

Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO.

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http://dx.doi.org/10.1373/clinchem.2017.281170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049699PMC
December 2017

Prevalence of Rare Hemoglobin Variants Identified During Measurements of Hb A by Capillary Electrophoresis.

Clin Chem 2017 12 13;63(12):1901-1902. Epub 2017 Sep 13.

Department of Pathology University of Virginia School of Medicine Charlottesville, VA

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http://dx.doi.org/10.1373/clinchem.2017.276857DOI Listing
December 2017

Implementing a Reference Measurement System for C-Peptide: Successes and Lessons Learned.

Clin Chem 2017 Sep 23;63(9):1447-1456. Epub 2017 Jun 23.

National Institute for Biological Standards and Control, South Mimms, UK.

Background: Assessment of endogenous insulin secretion by measuring C-peptide concentrations is widely accepted. Recent studies have shown that preservation of even small amounts of endogenous C-peptide production in patients with type 1 diabetes reduces risks for diabetic complications. Harmonization of C-peptide results will facilitate comparison of data from different research studies and later among clinical laboratory results at different sites using different assay methods.

Content: This review provides an overview of the general process of harmonization and standardization and the challenges encountered with implementing a reference measurement system for C-peptide.

Summary: Efforts to harmonize C-peptide results are described, including those by the National Institute of Diabetes and Digestive and Kidney Diseases-led C-peptide Standardization Committee in the US, activities in Japan, efforts by the National Institute for Biological Standards and Control in the UK, as well as activities led by the Bureau International des Poids et Mesures and the National Metrology Institute in China. A traceability scheme is proposed along with the next steps for implementation. Suggestions are made for better collaboration to optimize the harmonization process for other measurands.
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http://dx.doi.org/10.1373/clinchem.2016.269274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575958PMC
September 2017

Measurement of Hemoglobin A1c in Patients With Sickle Cell Trait.

JAMA 2017 06;317(21):2237

Department of Pathology and Anatomical Sciences, University of Missouri, Columbia.

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http://dx.doi.org/10.1001/jama.2017.4643DOI Listing
June 2017

Validation of the Use of Trinity Biotech ultra2 as a Comparative Method for Hemoglobin A1c Measurements in the Presence of HbE and HbD-Punjab Traits.

Clin Chem 2017 02 15;63(2):608-610. Epub 2016 Dec 15.

Department of Pathology and Anatomical Sciences University of Missouri Columbia, Missouri.

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http://dx.doi.org/10.1373/clinchem.2016.266221DOI Listing
February 2017

Higher degree of glycation of hemoglobin S compared to hemoglobin A measured by mass spectrometry: Potential impact on HbA1c testing.

Clin Chim Acta 2016 Jul 22;458:40-3. Epub 2016 Apr 22.

Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, United States. Electronic address:

Background: Glycated hemoglobin (GHb), reported as HbA1c, is used as marker of long-term glycemia for diabetic patients. HbA1c results from boronate affinity methods are generally considered to be unaffected by most hemoglobin variants; this assumes comparable glycation of variant and non-variant (HbAA) hemoglobins. In this report, glycation of HbA beta chain (βA) and HbS beta chain (βS) for the most common Hb variant trait (HbAS) are examined.

Methods: We analyzed 41 blood samples from subjects with HbAS, both with and without diabetes. Using LC-MS, ratios of glycated HbS to glycated HbA were determined by comparison of areas under the curves from extracted ion chromatograms.

Results: Glycation of βS chains was significantly higher (p<0.001) than βA chains; this difference was consistent across subjects. Total (α+β) glycated HbAS was theoretically estimated to be ~5% higher than glycated HbAA.

Conclusion: This novel mass-spectrometric approach described allows for relative quantification of glycated forms of βS and βA. Although βS glycation was significantly higher than that of βA, the difference in total glycation of HbAS versus HbAA was smaller and unlikely to impact clinical interpretation of boronate affinity HbA1c results. These data support the continued use of boronate affinity to measure HbA1c in patients with HbAS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068909PMC
http://dx.doi.org/10.1016/j.cca.2016.04.027DOI Listing
July 2016

Effects of hemoglobin C, D, E and S traits on measurements of hemoglobin A1c by twelve methods.

Clin Chim Acta 2016 Apr 29;455:80-3. Epub 2016 Jan 29.

Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, United States.

Background: Hemoglobin C, D Punjab, E or S trait can interfere with hemoglobin A1c (HbA1c) results. We assessed whether they affect results obtained with 12 current assay methods.

Methods: Hemoglobin AA (HbAA), HbAC, HbAD Punjab, HbAE and HbAS samples were analyzed on one enzymatic, nine ion-exchange HPLC and two Capillary Electrophoresis methods. Trinity ultra(2) boronate affinity HPLC was the comparative method. An overall test of coincidence of least-squared linear regression lines was performed to determine if HbA1c results were statistically significantly different from those of HbAA samples. Clinically significant interference was defined as >7% difference from HbAA at 6 or 9% HbA1c compared to ultra(2) using Deming regression.

Results: All methods showed statistically significant effects for one or more variants. Clinically significant effects were observed for the Tosoh G8 variant mode and GX (all variants), GX V1.22 (all but HbAE) and G11 variant mode (HbAC). All other methods (Abbott Architect c Enzymatic, Bio-Rad D-100, Variant II NU and Variant II Turbo 2.0, Menarini HA-8180T thalassemia mode and HA-8180V variant mode, Sebia Capillarys 2 and Capillarys 3) showed no clinically significant differences.

Conclusions: Several methods showed clinically significant interference with HbA1c results from one or more variants which could adversely affect patient care.
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http://dx.doi.org/10.1016/j.cca.2016.01.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966613PMC
April 2016

Two-step ion-exchange chromatographic purification combined with reversed-phase chromatography to isolate C-peptide for mass spectrometric analysis.

J Sep Sci 2016 Feb 28;39(4):676-81. Epub 2016 Jan 28.

University of Missouri, School of Medicine, One Hospital Drive, Columbia, MO, USA.

A liquid chromatography with mass spectrometry on-line platform that includes the orthogonal techniques of ion exchange and reversed phase chromatography is applied for C-peptide analysis. Additional improvement is achieved by the subsequent application of cation- and anion-exchange purification steps that allow for isolating components that have their isoelectric points in a narrow pH range before final reversed-phase mass spectrometry analysis. The utility of this approach for isolating fractions in the desired "pI window" for profiling complex mixtures is discussed.
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http://dx.doi.org/10.1002/jssc.201500989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053671PMC
February 2016

Quality of HbA1c Measurement in Trinidad and Tobago.

J Diabetes Sci Technol 2016 05 3;10(3):768-71. Epub 2016 May 3.

Departments of Pathology & Anatomical Sciences and Child Health, University of Missouri School of Medicine, Columbia, MO, USA

Background: Monitoring of HbA1c is the standard of care to assess diabetes control. In Trinidad & Tobago (T&T) there are no existing data on the quality of HbA1c measurement. Our study examined the precision and accuracy of HbA1c testing in T&T.

Methods: Sets of 10 samples containing blinded duplicates were shipped to laboratories in T&T. This exercise was repeated 6 months later. Precision and accuracy were estimated for each laboratory/method.

Results: T&T methods included immunoassay, capillary electrophoresis, and boronate affinity binding. Most, but not all, laboratories demonstrated acceptable precision and accuracy.

Conclusions: Continuous oversight of HbA1c testing (eg, through proficiency testing) in T&T is recommended. These results highlight the lack of oversight of HbA1c testing in some developing countries.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038524PMC
http://dx.doi.org/10.1177/1932296815609620DOI Listing
May 2016

Evaluation of hemoglobin A1c measurement by Capillarys 2 electrophoresis for detection of abnormal glucose tolerance in African immigrants to the United States.

Clin Chim Acta 2015 Jun 8;446:54-60. Epub 2015 Apr 8.

Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States. Electronic address:

Background: Hemoglobin A1c (HbA1c) is used to monitor long-term glycemic control in individuals with diabetes, guide therapy, predict the risk of microvascular complications, and more recently to diagnose diabetes. An automated liquid-flow capillary electrophoresis method was recently developed to measure HbA1c using the Capillarys 2 Flex Piercing instrument.

Methods: Analytical evaluation was performed at 2 clinical centers. A clinical analysis was conducted in 109 African-born individuals, 24% of whom have variant hemoglobin (HbAS or HbAC). Abnormal glucose tolerance (which includes both diabetes and prediabetes) was defined as 2h glucose of ≥ 140 mg/dl (7.8 mmol/l) during an oral glucose tolerance test.

Results: Interlaboratory CVs were ≤ 2.1%. The method showed satisfactory correlation with 2 other analyzers that measure HbA1c by high-performance liquid chromatography. Neither labile HbA1c, carbamylated hemoglobin, uremia, bilirubin nor common hemoglobin variants (HbC/HbS/HbE) interfered. Forty-five individuals (41%) had abnormal glucose tolerance. The sensitivity of HbA1c for diagnosing abnormal glucose tolerance was 38%, 36% and 42% for total, normal and variant hemoglobin groups, respectively.

Conclusions: The analytical performance of HbA1c on the Capillarys 2 is suitable for clinical application. Variant hemoglobin in Africans did not interfere with the detection of abnormal glucose tolerance by HbA1c measured on the Capillarys 2.
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http://dx.doi.org/10.1016/j.cca.2015.03.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449818PMC
June 2015

Investigation of 2 models to set and evaluate quality targets for hb a1c: biological variation and sigma-metrics.

Clin Chem 2015 May 3;61(5):752-9. Epub 2015 Mar 3.

Diabetes and Endocrine Department, Ichikawa General Hospital, Ichikawa, Japan.

Background: A major objective of the IFCC Task Force on Implementation of HbA1c Standardization is to develop a model to define quality targets for glycated hemoglobin (Hb A1c).

Methods: Two generic models, biological variation and sigma-metrics, are investigated. We selected variables in the models for Hb A1c and used data of external quality assurance/proficiency testing programs to evaluate the suitability of the models to set and evaluate quality targets within and between laboratories.

Results: In the biological variation model, 48% of individual laboratories and none of the 26 instrument groups met the minimum performance criterion. In the sigma-metrics model, with a total allowable error (TAE) set at 5 mmol/mol (0.46% NGSP), 77% of the individual laboratories and 12 of 26 instrument groups met the 2σ criterion.

Conclusions: The biological variation and sigma-metrics models were demonstrated to be suitable for setting and evaluating quality targets within and between laboratories. The sigma-metrics model is more flexible, as both the TAE and the risk of failure can be adjusted to the situation-for example, requirements related to diagnosis/monitoring or international authorities. With the aim of reaching (inter)national consensus on advice regarding quality targets for Hb A1c, the Task Force suggests the sigma-metrics model as the model of choice, with default values of 5 mmol/mol (0.46%) for TAE and risk levels of 2σ and 4σ for routine laboratories and laboratories performing clinical trials, respectively. These goals should serve as a starting point for discussion with international stakeholders in the field of diabetes.
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http://dx.doi.org/10.1373/clinchem.2014.235333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946649PMC
May 2015

Effects of 49 Different Rare Hb Variants on HbA1c Measurement in Eight Methods.

J Diabetes Sci Technol 2015 Jul 17;9(4):849-56. Epub 2015 Feb 17.

Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT, USA.

Background: Previous studies have shown interference with HbA1c measurement from the 4 most common heterozygous Hb variants (HbAS, HbAE, HbAC, and HbAD) with some assay methods. Here we examine analytical interference from 49 different less common variants with 7 different HbA1c methods using various method principles.

Methods: Hb variants were screened using the Bio-Rad Variant or Variant II beta thal short program, confirmed by alkaline and acid electrophoresis, and identified by sequence analysis. The Trinity ultra2 boronate affinity high-performance liquid chromatography (HPLC) method and Roche Tinaquant immunoassay were used as primary and secondary comparative methods, respectively, since these methods are least likely to show interference from Hb variants. Other methods included were the Tosoh G7 and G8, Bio-Rad D-10 and Variant II Turbo, Diazyme Enzymatic, and Sebia Capillarys 2 Flex Piercing. To eliminate any inherent calibration bias, results for each method were adjusted using regression verses the ultra2 with nonvariant samples. Each method's calibration-adjusted results were compared and judged to be acceptable if within the 99% prediction interval of the regression line for nonvariant samples.

Results: Almost all variant samples were recognized as such by the ion-exchange HPLC methods by the presence of abnormal peaks or results outside the reportable range. For most variants, interference was seen with 1 or more of the ion-exchange methods. Following manufacturer instructions for interpretation of chromatograms usually, but not always, prevented reporting of inaccurate results.

Results: Laboratories must be cautious about reporting results when the presence of a variant is suspected.
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http://dx.doi.org/10.1177/1932296815572367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525651PMC
July 2015

Performance of hemoglobin A1c assay methods: good enough?

Authors:
Randie R Little

Clin Chem 2014 Aug 17;60(8):1031-3. Epub 2014 Jun 17.

Diabetes Diagnostic Laboratory, Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO.

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http://dx.doi.org/10.1373/clinchem.2014.225789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757849PMC
August 2014

Comparing analytic performance criteria: evaluation of HbA1c certification criteria as an example.

Clin Chim Acta 2014 Jun 8;433:259-63. Epub 2014 Apr 8.

Department of Pathology & Anatomical Sciences, University of Missouri, Columbia School of Medicine, 1 Hospital Drive, Columbia, MO 65212, United States; Department of Child Health, University of Missouri, Columbia School of Medicine, 1 Hospital Drive, Columbia, MO 65212, United States.

Background: Direct comparison of analytical performance criteria that utilize different statistical approaches can be problematic. We describe a mathematical approach to compare performance criteria for hemoglobin A1c (HbA1c) analysis used by the NGSP standardization program and the College of American Pathologists (CAP) to enhance consistency between the schemes.

Methods: The imprecision (CV) and bias combinations required to pass each criterion at probabilities of 0.95, 0.99 and 0.999 were calculated and used to construct contour plots to compare them. The CV/bias requirements were calculated mathematically for the 2011-2012 CAP (3/3 results within ±7% of the target) and different proposed NGSP (33/40 to 40/40 results within ±7% of the target) criteria, and using computer simulations for the existing NGSP criterion (95% confidence interval of the differences between the method and NGSP within ±0.75% HbA1c).

Results: Requiring 37 of 40 results to be within ±7% of the NGSP target best matched the CAP criterion at zero bias (95% chance of passing).

Conclusions: The NGSP Steering Committee recommended a certification criterion of 37 of 40 results within ±7% of the NGSP (reduced to ±6% in 2014). The described evaluation approach may be useful in other situations where comparison of different performance criteria is desired.
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http://dx.doi.org/10.1016/j.cca.2014.03.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041663PMC
June 2014

Isotope dilution assay in peptide quantification: the challenge of microheterogeneity of internal standard.

Proteomics Clin Appl 2013 Dec 18;7(11-12):825-8. Epub 2013 Oct 18.

School of Medicine, University of Missouri, Columbia, MO, USA.

Isotope dilution analysis allows quantitation of elements and different compounds in complex mixtures. The quantitation is based on a known amount of reference material (internal standard, IS) added to a sample that makes the result critically dependent on the value assigned to the standard. In the case of peptides, IS concentration is determined by nitrogen and amino acid analysis while purity is normally assessed by methods such as chromatography or electrophoresis that might not be able to detect many possible amino acid modifications, either naturally occurring or chemically induced. Microheterogeneity of the IS, if it is not accounted for when assigning a reference value to the standard, results in highly overestimated values in target analyte quantitation. In this viewpoint article, we illustrate the problem of internal standard microheterogeneity by analyzing synthetic human C-peptide labeled analogs.
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http://dx.doi.org/10.1002/prca.201200130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191039PMC
December 2013

Measurement of Hba(1C) in patients with chronic renal failure.

Clin Chim Acta 2013 Mar 12;418:73-6. Epub 2013 Jan 12.

Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, One Hospital Dr., Columbia, MO 65212, USA.

Background: Carbamylated hemoglobin (carbHb) is reported to interfere with measurement and interpretation of HbA(1c) in diabetic patients with chronic renal failure (CRF). There is also concern that HbA1c may give low results in these patients due to shortened erythrocyte survival.

Methods: We evaluated the effect of carbHb on HbA(1c) measurements and compared HbA(1c) with glycated albumin (GA) in patients with and without renal disease to test if CRF causes clinically significant bias in HbA(1c) results by using 11 assay methods. Subjects included those with and without renal failure and diabetes. Each subject's estimated glomerular filtration rate (eGFR) was used to determine the presence and degree of the renal disease. A multiple regression model was used to determine if the relationship between HbA(1c) results obtained from each test method and the comparative method was significantly (p<0.05) affected by eGFR. These methods were further evaluated for clinical significance by using the difference between the eGRF quartiles of >7% at 6 or 9% HbA(1c). The relationship between HbA(1c) and glycated albumin (GA) in patients with and without renal failure was also compared.

Results: Some methods showed small but statistically significant effects of eGFR; none of these differences were clinically significant. If GA is assumed to better reflect glycemic control, then HbA(1c) was approximately 1.5% HbA(1c) lower in patients with renal failure.

Conclusions: Although most methods can measure HbA(1c) accurately in patients with renal failure, healthcare providers must interpret these test results cautiously in these patients due to the propensity for shortened erythrocyte survival in renal failure.
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http://dx.doi.org/10.1016/j.cca.2012.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757846PMC
March 2013

The long and winding road to optimal HbA1c measurement.

Clin Chim Acta 2013 Mar 11;418:63-71. Epub 2013 Jan 11.

Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, One Hospital Dr., Columbia, MO 65212, USA.

The importance of hemoglobin A1c (HbA1c) as an indicator of mean glycemia and risks for complications in patients with diabetes mellitus was established by the results of long-term clinical trials, most notably the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), published in 1993 and 1998 respectively. However, clinical application of recommended HbA1c targets that were based on these studies was difficult due to lack of comparability of HbA1c results among assay methods and laboratories. Thus, the National Glycohemoglobin Standardization Program (NGSP) was initiated in 1996 with the goal of standardizing HbA1c results to those of the DCCT/UKPDS. HbA1c standardization efforts have been highly successful; however, a number of issues have emerged on the "long and winding road" to better HbA1c, including the development of a higher-order HbA1c reference method by the International Federation of Clinical Chemistry (IFCC), recommendations to use HbA1c to diagnose as well as monitor diabetes, and point-of-care (POC) HbA1c testing. Here, we review the past, present and future of HbA1c standardization and describe the current status of HbA1c testing, including limitations that healthcare providers need to be aware of when interpreting HbA1c results.
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http://dx.doi.org/10.1016/j.cca.2012.12.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762213PMC
March 2013

Human C-peptide Quantitation by LC-MS Isotope-Dilution Assay in Serum or Urine Samples.

J Chromatogr Sep Tech 2013 27;4(3). Epub 2013 Mar 27.

University of Missouri, School of Medicine, Columbia MO, USA.

In this communication we report a simple and efficient approach to C-peptide quantitation using isotope dilution mass-spectrometry analysis. The method facilitates quantitation of C-peptide levels at least one order of magnitude lower compared to concentration levels achieved with an IDA method reported previously. The improvement was due to more intensive sample preparation procedure that, in turn, makes it possible to increase the sample load without a corresponding increase in matrix effects. We also show the results of a comparison study with a second laboratory using a similar previously reported method for C-peptide quantitation.
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http://dx.doi.org/10.4172/2157-7064.1000172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961834PMC
March 2013

Analysis of the accuracy and precision of the Axis-Shield Afinion hemoglobin A1c measurement device.

Authors:
Randie R Little

J Diabetes Sci Technol 2012 Mar 1;6(2):387-8. Epub 2012 Mar 1.

Department of Pathology & Anatomical Sciences, Columbia, Missouri 65212, USA.

Point-of-care (POC) hemoglobin A1c measurement is now used by many physicians to make more timely decisions on therapy changes. A few studies have highlighted the drawbacks of some POC methods, e.g., poor precision and lot-to-lot variability. Evaluating performance in the clinical setting is difficult because there is minimal proficiency testing data on POC methods. In this issue of Journal of Diabetes Science and Technology, Wood and colleagues describe their experience with the Afinion method in a pediatric clinic network, comparing these results to another POC method as well as to a laboratory high-performance liquid chromatography method. Although they conclude that the Afinion exhibits adequate performance, they do not evaluate lot-to-lot variability. As with laboratory methods, potential assay interferences must also be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380783PMC
http://dx.doi.org/10.1177/193229681200600225DOI Listing
March 2012