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The National Glycohemoglobin Standardization Program: A Five-Year Progress Report

¹ Departments of Child Health and Pathology, University of Missouri School of Medicine, 1 Hospital Dr., Columbia, MO 65212.

² Centers for Disease Control and Prevention, Division of Laboratory Sciences, National Center for Environmental Health (F25), 4770 Buford Hwy. NE, Chamblee, GA 30341-3724.

³ Brigham & Women’s Hospital, Department of Pathology, Harvard Medical School, Thorn 430, 75 Francis St., Boston, MA 02115.

^aAddress correspondence to this author at: Department of Child Health, Room M767, University of Missouri School of Medicine, 1 Hospital Dr., Columbia, MO 65212. Fax 573-884-8823; e-mail LittleR{at}health.missouri.edu.

	Abstract

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
Background: The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) demonstrated conclusively that risks for complications in patients with diabetes are directly related to glycemic control, as measured by glycohemoglobin (GHB). In 1994, one year after the DCCT results were reported, the American Diabetes Association (ADA) set specific diabetes treatment goals. However, 1993 College of American Pathologists (CAP) Survey results indicated a lack of comparability of GHB test results among methods and laboratories that represented a major obstacle to meaningful implementation of the ADA guidelines. Thus, an AACC subcommittee was formed in 1993 to develop a standardization program that would enable laboratories to report DCCT-traceable GHB results. This program was implemented in 1996 by the National Glycohemoglobin Standardization Program (NGSP) Steering Committee.

Approach: We review the NGSP process and summarize progress in standardization through analysis of CAP data.

Content: Since 1996, the number of methods and laboratories certified by the NGSP as traceable to the DCCT has steadily increased. CAP GH2-B survey results reported in December 2000 show marked improvement over 1993 data in the comparability of GHB results. In 2000, 90% of surveyed laboratories reported GHB results as hemoglobin A_1c (HbA_1c) or equivalent, compared with 50% in 1993. Of laboratories reporting HbA_1c in 2000, 78% used a NGSP-certified method. For most certified methods in 2000, between-laboratory CVs were <5%. For all certified methods in 2000, the mean percent HbA_1c was within 0.8% HbA_1c of the NGSP target at all HbA_1c concentrations.

Summary: The majority of laboratories in the US are now reporting results that are traceable to DCCT/UKPDS outcomes.

	Introduction

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
The landmark Diabetes Control and Complications Trial (DCCT), ¹ completed in 1993, showed that the risk for development and progression of the chronic complications of type 1 diabetes is closely related to the degree of glycemic control, as assessed by glycohemoglobin [(GHB); specifically hemoglobin A_1c (HbA_1c)] determinations (1)(2). The study also provided a large body of data relating HbA_1c values to mean blood glucose. On the basis of the DCCT results, the American Diabetes Association (ADA) now recommends that a primary treatment goal in diabetes should be blood glucose control at least equal to that achieved in the intensively treated cohort in the DCCT (3). They further state specific HbA_1c targets based on the DCCT results; a goal of 7% and action suggested at >8% (4). The United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, showed results similar to the DCCT in patients with type 2 diabetes (5).

The correlation between GHB and outcome risks demonstrated in the DCCT and later in the UKPDS underscore the need to measure GHB with high precision and in such a manner that results can be directly related to these studies and therefore to outcome risks. However, in 1993, at the end of the DCCT, GHB assay methods were not standardized among methods or laboratories, making it difficult for physicians and patients to relate test results to DCCT-based treatment goals.

Because of the positive impact that standardization of GHB determinations would have on the care of diabetic patients, and in anticipation of the report of DCCT results, the AACC Standards Committee established a GHB standardization subcommittee in April 1993. The goal of the subcommittee was to develop a plan for GHB standardization that would ultimately allow individual clinical laboratories to relate their GHB assay results to those from the DCCT. This would allow individual clinical laboratories to provide diabetic patients and their healthcare providers with test results that could be related directly to risks for development and/or progression of diabetes-related chronic complications.

Although the DCCT was completed in 1993, the GHB assay systems from the study remained in place as part of another National Institutes of Health-sponsored long-term diabetes study called the Epidemiology of Diabetes Interventions and Complications (EDIC) (6). To initiate a standardization program in a timely fashion, the AACC subcommittee on GHB standardization recommended that the DCCT reference method be used as the designated comparison method for GHB standardization while studies were being performed to evaluate candidate definitive and reference methods and to develop purified GHB standards.

Early efforts to standardize GHB values among clinical laboratories by use of a "universal calibrator" were feasible with some assay methods (7)(8). Later studies (9)(10) showed, however, that such an approach did not work for several existing methods. It was found that materials prepared for use as calibrators, quality-control materials, and proficiency-testing samples were often subjected to preparative processes that could cause them to yield results that differed appreciably from those of patient specimens, i.e., matrix effects (10). However, if appropriate calibrators or conversion equations were used for each method, calibration was feasible with all methods (11). Therefore, because an important goal was to allow standardization of all assay methods regardless of the methodology used, the GHB standardization subcommittee proposed that standardization to the DCCT reference could be performed best at the manufacturing level, where the most appropriate materials and standardization format for each method could be determined. Verification of method traceability was to be based on fresh sample comparisons with the Designated Comparison Method.

Once the development of a standardization protocol was completed, the subcommittee was dissolved and the National Glycohemoglobin Standardization Program (NGSP) was organized to implement the protocol developed by the AACC subcommittee. The NGSP approach to standardization of GHB was modeled after the Cholesterol Reference Method Laboratory Network program (12), which provides a means for manufacturers to establish traceability to the National Reference System for Cholesterol via split sample comparisons. Here we describe the NGSP, changes that were made in the protocol based on certification and proficiency testing (PT) data during first 3 years of implementation, and the resulting improvements seen in GHB measurements as indicated by PT data.

	The NGSP

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
ngsp laboratory network and oversight
The NGSP consists of a Steering Committee and a Laboratory Network. The flow chart in Fig. 1 outlines the basic components of the NGSP and the way in which they interact with each other as well as with manufacturers and clinical laboratories.

View larger version (31K): [in this window] [in a new window]   Figure 1. Flowchart showing NGSP organization and processes.

steering committee
The Steering Committee works with the Laboratory Network to implement the GHB Standardization Program according to the protocol. The committee is responsible for reviewing policy/protocol changes and certification data submitted by the Laboratory Network.

laboratory network
The Laboratory Network consists of an Administrative Core (NETCORE), a Central Primary Reference Laboratory (CPRL), back-up Primary Reference Laboratories (PRLs) in the US and in Europe, and Secondary Reference Laboratories (SRLs) in the US and in Europe. By mid-1996, a Laboratory Network consisting of a CPRL, PRLs, and SRLs was established; monitoring of each network laboratory began in May 1996. SRL methods now include ion-exchange HPLC, affinity HPLC, capillary electrophoresis, and immunoassay (see list of network laboratory participants in the Appendix).

NETCORE.
The Administrative Core coordinates the certification process and communicates directly with the Steering Committee. The Core analyzes all certification and network monitoring data, sends certification and monitoring data to the Steering Committee, and issues certificates to laboratories and manufacturers after review of the data by the Steering Committee.

CPRL.
The CPRL analyzes GHB (HbA_1c) by HPLC using Bio-Rex 70 resin and according to the existing CPRL method protocol used throughout the DCCT (13) and sets the initial calibration for the standardization program based on the "set-point" used in the DCCT. Although the shortcomings of this particular method are well known with regard to its specificity (e.g., interference from HbF, variant hemoglobins, and nonglucose adducts) and low throughput, its long-term stability was the primary factor in its selection as the anchor or point of reference for the NGSP (Fig. 2 ). The CPRL method has shown long-term CVs of <3% throughout and after the DCCT. Backup PRLs and SRLs calibrate their assays so that results from fresh blood specimens agree with the CPRL. The CPRL provides comparison data for certification of network laboratories and administers a monitoring program for all certified PRLs and SRLs.

View larger version (22K): [in this window] [in a new window]   Figure 2. Mean HbA1c (± SD) measured by the CPRL for one quality-control specimen (frozen hemolysate) during and after the DCCT (1984–2000). The mean (gray solid line) was established based on the first 34 results in 1984.

PRLs.
PRLs serve as back-up laboratories for the CPRL to ensure that the CPRL function would continue without interruption in the event that the CPRL could not meet the program needs. All PRLs analyze GHB (HbA_1c) by the Designated Comparison Method according to the CPRL method protocol. PRLs must be certified as traceable to the CPRL method (see discussion of criteria below).

SRLs.
SRLs work directly with manufacturers to assist them in standardizing their methods and in providing comparison data for certification of traceability. Each SRL analyzes GHB by a precise method (documented total imprecision 3%) that is calibrated to the Designated Comparison Method. Although most SRLs use methods that are commercially available, SRL methods are specifically calibrated for the NGSP to match the CPRL. SRLs must be certified as traceable to the CPRL method according to specific, strict criteria (see "Certification Criteria" below). In addition, the precision and bias of network laboratories are evaluated monthly to ensure that they are within specific limits of the CPRL (see "Performance Monitoring of Network Laboratories" below).

certification of network laboratories
A proposed network laboratory (PRL or SRL) must perform precision testing according to NCCLS EP5-A guidelines (14) and participate in a fresh-blood sample comparison (n = 100) for estimation of bias from the CPRL according to modified NCCLS EP9-A guidelines (15).

performance monitoring of network laboratories
Monthly surveys are administered by the CPRL to monitor performance of the network PRLs and SRLs. Each month, the CPRL ships 10 fresh whole-blood specimens over the desired clinical range (4–14% HbA_1c) to each network laboratory within 2 days of collection. The CPRL, PRLs, and SRLs analyze the specimens in two separate analytical runs on 2 separate days. Data analysis includes a measure of precision (SD of the differences in replicates) and bias (mean of the differences between the network laboratory and the CPRL). An example of one SRL monthly monitoring report showing precision and bias over a 12-month period is shown in Fig. 3 .

View larger version (23K): [in this window] [in a new window]   Figure 3. Representative sample of NGSP network monitoring data for one SRL over a 12-month period showing monthly precision and bias. (A), precision monitoring. Sp is the estimate of the SD of the difference in sample replicates. The solid line at 0.229 is the 99th percentile of the sampling distribution around a target SD of 0.15 (dotted line), and the dashed line at 0.203 is the 95th percentile of the sampling distribution (warning limit). (B), bias monitoring. Solid horizontal lines at ± 0.35 indicate the NGSP monitoring limit.

ngsp protocol
The NGSP Laboratory Network interacts with laboratories and manufacturers through three different processes: calibration, certification, and PT (Fig. 1 ).

Calibration.
The process by which a method is standardized so that results are comparable to those of the NGSP Network is an informal one and is determined by the manufacturer. The process depends on the specific method, e.g., calibration may be accomplished by assignment of calibrator values or by a conversion equation.

Certification.
Certification is a formal process consisting of assessments of both precision and bias from the NGSP (DCCT equivalent results). Both manufacturers and clinical laboratories can participate in this process. Precision testing follows NCCLS EP5-A guidelines (14). Method comparison for bias estimation is done with fresh (or fresh frozen) blood samples (n = 40), with duplicate analysis by the manufacturer or laboratory being certified and a SRL. Methods and laboratories that pass NGSP certification criteria are awarded a certificate of traceability to the DCCT.

PT.
The ADA recommends that all laboratories participate in a PT program administered by the College of American Pathologists (CAP) that uses fresh blood samples (16). Unlike other GHB PT surveys provided in the US, the CAP GH2 survey provides pooled fresh blood specimens at three GHB concentrations with target values assigned by the NGSP Network (mean of results from NGSP SRLs). Matrix effects are avoided by use of fresh blood, and sample deterioration is minimized by shipment on cold packs within 1 week of collection. The NGSP value assignment allows laboratories to directly compare their results to those of the NGSP/DCCT as well as to other laboratories that use the same method. PT data are used to assess the effectiveness of the standardization program by (a) estimation of bias from the target (e.g., by laboratory, by method, by method type) and by (b) interlaboratory comparability within and between method peer groups.

certification criteria
Manufacturers and laboratories are awarded Certificates of Traceability to the DCCT for successfully completing precision testing and fresh sample comparisons for the specific reagent lots, calibrator lots, and instrumentation used. Final certification of traceability is issued by the NETCORE after review of the data by the Steering Committee. It is recommended that manufacturers recertify their methods annually. Current certification criteria are described below.

Network laboratory certification.
PRLs and SRLs must fulfill the following criteria for network laboratory certification: (a) total imprecision (CV) must not be significantly (² analysis) >3%; (b) no more than one within-method and one between-method outlier is acceptable; and (c) the 95% confidence interval (CI) for predicted bias should overlap the ± 3% range of the CPRL at two GHB concentrations (6% and 9% HbA_1c). All data analyses are performed by the NETCORE, according to NCCLS EP5-A (precision) and modified EP9-A (bias) guidelines.

Manufacturer and level II laboratory certification.
For a commercial method or a laboratory to be considered traceable to the DCCT (a) total imprecision (CV) must not be statistically significantly >5% (14) and (b) the 95% CI of the differences between methods (test method vs SRL) must fall within the clinically significant limits of ± 1% GHB (17). Outliers (more than the mean + 3 SD of differences between pairs) are identified but used for investigational purposes only, and not to pass or fail a method.

Level I laboratory certification.
This type of certification, which includes both yearly certification and quarterly monitoring, is recommended for large laboratories that are involved in research studies or clinical trials where long-term precision of GHB measurement is critical. The certification process is the same as for manufacturers, but the precision and bias criteria are more stringent: (a) total imprecision (CV) must not be statistically significantly >3% (14), and (b) the 95% CI of the differences between methods (test method vs SRL) must fall within ± 0.75% GHB (17). The quarterly monitoring process and criteria are identical to those used for monthly network laboratory monitoring.

	Changes in Certification Criteria in December 1999

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
Before December 1999, the certification criteria for manufacturers and laboratories were similar to the criteria used for network laboratories; precision analysis followed NCCLS EP-5 and bias estimation analysis followed modified NCCLS EP-9 guidelines. When 3 years of certification and PT data were evaluated, there appeared to be room for improvement. A few methods that passed the NGSP certification criteria showed considerable scatter around the regression line when compared with a NGSP network laboratory. CAP survey data confirm that methods with large scatter do not perform as well in the field as methods with less scatter. Fig. 4 shows certification data from two methods that passed NGSP certification using modified NCCLS EP-9 guidelines. In both cases, the methods show little bias from the NGSP network laboratory, and both would pass the old bias criteria. However, one method shows considerable scatter around the regression line. Because NCCLS EP9-A requires only that the 95% CI overlap the decision limit, which is ± 5% of the network laboratory result at 6% and 9% HbA_1c, the amount of scatter in individual results is not taken into account. In fact, it is easier for methods that show more scatter around the regression line to pass the bias criteria because this widens the 95% CI of the predicted bias, making it easier to overlap the 5% limit.

View larger version (32K): [in this window] [in a new window]   Figure 4. Scatter plots and Bland–Altman plots of a method with small bias and small scatter (A) and a method with small bias but large scatter (B). Dashed lines on regression plots (left) are the regression lines; solid lines are y = x. Thick solid lines on Bland–Altman plots (right) indicate the ± 1% HbA1c limits; dashed lines indicate the mean and 95% CI of the differences between test method and SRL.

The NGSP addressed this problem by changing the bias criteria for certification of manufacturer and level I and II laboratories from estimation of bias according to NCCLS EP9-A (15) to assessment of agreement according to Bland and Altman, indicated in Table 1 (17). The method shown in Fig. 4B would fail the new assessment of agreement criteria. In addition, the outlier criteria were changed slightly and were no longer used to pass or fail a method (Table 1 ).

	Progress in Standardization

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
certified methods and laboratories
The NGSP certifies methods and laboratories each quarter; 14 methods from five manufacturers were certified during the first year (December 1996 through September 1997). Between December 1996 and December 2000, 45 different methods and 14 different laboratories were certified. A current list of certified methods and laboratories can be found on the NGSP website (www.missouri.edu/diabetes/ngsp.html).

cap results
In 2000, based on CAP GH2 2000B summary report data (18), 90% of laboratories reported results as HbA_1c or equivalent, compared with only 50% in 1993 when the DCCT ended (19) and 66% in 1996 when the NGSP first began. Of those laboratories reporting results as HbA_1c, 78% (70% of the total) used a NGSP-certified method. The mean, high, and low values for each method, compared with the DCCT/NGSP target values in 1993 and 2000, are shown in Fig. 5 . Compared with results in 1993, many more methods and laboratories reported results that were close to the DCCT target. For most certified methods in 2000, between-laboratory CVs were <5%. For all certified methods in 2000, the mean %HbA_1c was within 0.6%, 0.5%, and 0.8% HbA_1c of the NGSP target at the low, middle, and high HbA_1c, respectively (CAP 2000 GH2-B). Overall, NGSP-certified methods are more precise and consistent among laboratories.

View larger version (19K): [in this window] [in a new window]   Figure 5. CAP survey results in 1993 (EC-C) and 2000 (GH2-B) showing the mean, high, and low GHB values for each method peer group reported as HbA1c (), HbA1 (), and total GHB (•). Dotted line, DCCT Target value. (Data used with permission of the College of American Pathologists.)

	Use of DCCT-Traceable Results

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
Since 1997, the ADA has recommended that "laboratories use only GHB assay methods that have passed certification testing" (16). In 1999, the Veterans Health Administration of the US Department of Veterans Affairs announced that all Veterans Affairs hospital laboratories would be required to use NGSP-certified methods (VHA Directive 99-042). The January 2000 UK Consensus Statement advises laboratories to report results that are "DCCT aligned" (20).

Despite the use of many different GHB assay methodologies, 70% of laboratories are currently using NGSP-certified methods and are thus reporting DCCT-traceable results (18). DCCT-traceable results are now being used on a national level in the US as a means of measuring the quality of diabetes care and educating people with diabetes and their healthcare providers. For example, HbA_1c is 1 of 11 variables used by the ADA to assess diabetes care for its Provider Recognition Program. For this program, the frequency of HbA_1c measurement and the proportion of patients with HbA_1c <8% and <10% (by a NGSP-certified method) is assessed. The Diabetes Quality Improvement Project "accountability measures" include the percentage of patients receiving one or more GHB tests per year and the percentage of patients with HbA_1c >9.5% (those at highest risk for complications); these measures were subsequently adopted by the National Committee for Quality Assurance. More recently, a consensus statement from the American Medical Association, the Joint Commission on Accreditation of Healthcare Organizations, and the National Committee for Quality Assurance recommended the use of Diabetes Quality Improvement Project measures and use of certified methods. The National Diabetes Education Program will promote the ADA goals for diabetes treatment through the development and implementation of diabetes awareness and education activities. Standardization of GHB to an outcomes-based reference system is critical to these processes.

	International Standardization

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
At the international level, the IFCC established a working group in 1995. The focus of this group has been the development of a primary reference material and a reference method for HbA_1c. An IFCC Laboratory Network that uses mixtures of purified HbA_1c and HbA₀ to calibrate two different reference methods has been established (21). Efforts are underway to document the relationship between the IFCC and NGSP network results. Preliminary data show that IFCC HbA_1c results are significantly lower than NGSP results. The IFCC reference methods may eventually replace the existing CPRL method as the anchor or reference method for the NGSP, although evaluation of the long-term stability of the IFCC reference methods must first be validated. However, the adoption of IFCC numbers for reporting GHB results for patient care in the US would require careful consideration involving input and discussion from diabetes healthcare providers. Changing the NGSP reference method anchor would not be expected to have any effect on the NGSP certification process or the reporting of DCCT-traceable results.

	Summary

Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 
A standardization program for GHB based on the DCCT reference method has been developed. There is now widespread acceptance and implementation of the certification process. Most manufacturers in the US (and many outside the US) participate in the NGSP certification process on a consistent basis; some large reference laboratories have also become certified. Routine clinical laboratories are becoming increasingly aware of the necessity of using NGSP-certified methods for GHB analysis. There has also been a steady improvement in assay methods with respect to harmonization of results and improved precision. We conclude that the majority of laboratories in the US are reporting GHB test results that are traceable to DCCT- and UKPDS-determined outcome risks. GHB standardization should facilitate optimal use of ADA guidelines for routine patient care and proper interpretation of healthcare performance measures.

	Appendix

 

Appendix: NGSP Steering Committee members and Laboratory Network participants.

NGSP Steering Committee members NGSP Laboratory Network participants David E. Goldstein, MD, Chair K. Michael Parker, PhD CPRL: University of Missouri-Columbia  University of Missouri School of Medicine  The University Hospitals  Jack D. England, Shawn Connolly  Oklahoma City, OK  Columbia, MO  Jack D. England, Shawn Connolly  C. Patel Roberta G. Reed, PhD Randie R. Little, PhD  The Mary Imogene Bassett Hospital PRL1: Massachusetts General Hospital  University of Missouri School of Medicine  Lorna Lampert  Cooperstown, NY  Columbia, MO SRL3: University of Missouri-Columbia  Alethea Tennill David C. Robbins, MD Elaine W. Gunter, BS, MT(ASCP)  Medlantic Research Institute SRL4: Core Laboratory for Clinical Studies, Washington University  Centers for Disease Control and Prevention  Washington, DC  School of Medicine  Thomas G. Cole, Bill Nowatzke  Atlanta, GA David Sacks, MD SRL5: University of Missouri-Columbia  Brigham & Women’s Hospital  Randy Ellison Gary L. Myers, PhD  Harvard Medical School  Centers for Disease Control and Prevention  Boston, MA SRL6: University of Minnesota  Jean Bucksa, Maren Nowicki  Atlanta, GA Michael W. Steffes, MD, PhD EPRL, ESRL2 & 3: Queen Beatrix Hospital (Winterswijk, The Netherlands)  University of Minnesota David M. Nathan, MD  Minneapolis, MN  Cas W. Weykamp, Carla Siebelder  Massachusetts General Hospital ESRL 4 & 5: Ziekenhuis De Weezenlanden (Zvolle, The Netherlands) Sergey Vlasenko, PhD  Kor Miedema, Erma Lenters  Boston, MA  Bio-Rad Laboratories  Hercules, CA Lowry J. Messenger, PhD  LXN Corporation John Eckfeldt, MD, PhD X  San Diego, CA   (past member)  University of Minnesota  Minneapolis, MN

	Acknowledgments

 
The NGSP is supported in part by the Centers for Disease Control and Prevention through a funding contract (No. 200199900131). We wish to thank the NGSP network laboratories for their cooperation and high-quality data. We also thank Dr. Richard Madsen for statistical assistance in developing the NGSP criteria.

	Footnotes

 
¹ Nonstandard abbreviations: DCCT, Diabetes Control and Complications Trial; GHB, glycohemoglobin; Hb, hemoglobin; ADA, American Diabetes Association; UKPDS, United Kingdom Prospective Diabetes Study; NGSP, National Glycohemoglobin Standardization Program; PT, proficiency testing; NETCORE, Network Administrative Core; CPRL, Central Primary Reference Laboratory; PRL, Primary Reference Laboratory; SRL, Secondary Reference Laboratory; CAP, College of American Pathologists; and CI, confidence interval.

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Top Abstract Introduction The NGSP Changes in Certification... Progress in Standardization Use of DCCT-Traceable Results International Standardization Summary References

 

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				K. H. Kahler, M. Rajan, G. G. Rhoads, M. M. Safford, K. Demissie, S.-E. Lu, and L. M. Pogach Impact of Oral Antihyperglycemic Therapy on All-Cause Mortality Among Patients With Diabetes in the Veterans Health Administration Diabetes Care, July 1, 2007; 30(7): 1689 - 1693. [Abstract] [Full Text] [PDF]

				W. H. Herman Diabetes Epidemiology: Guiding Clinical and Public Health Practice: The Kelly West Award Lecture, 2006 Diabetes Care, July 1, 2007; 30(7): 1912 - 1919. [Full Text] [PDF]

				M. Reiter, S. Wirth, A. Pourazim, S. Puchner, M. Baghestanian, E. Minar, and R. A. Bucek Skin tissue cholesterol is not related to vascular occlusive disease Vascular Medicine, May 1, 2007; 12(2): 129 - 134. [Abstract] [PDF]

				D. M. Nathan, J. B. Buse, M. B. Davidson, R. J. Heine, R. R. Holman, R. Sherwin, and B. Zinman Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care, August 1, 2006; 29(8): 1963 - 1972. [Full Text] [PDF]

				M. S. Faulkner, L. Quinn, J. H. Rimmer, and B. H. Rich Cardiovascular Endurance and Heart Rate Variability in Adolescents With Type 1 or Type 2 Diabetes Biol Res Nurs, July 1, 2005; 7(1): 16 - 29. [Abstract] [PDF]

				D. B. Sacks and for the ADA/EASD/IDF Working Group of the HbA1c As Global Harmonization of Hemoglobin A1c Clin. Chem., April 1, 2005; 51(4): 681 - 683. [Full Text] [PDF]

				M. Steffes, P. Cleary, D. Goldstein, R. Little, H.-M. Wiedmeyer, C. Rohlfing, J. England, J. Bucksa, M. Nowicki, and the DCCT/EDIC Research Group Hemoglobin A1c Measurements over Nearly Two Decades: Sustaining Comparable Values throughout the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study Clin. Chem., April 1, 2005; 51(4): 753 - 758. [Abstract] [Full Text] [PDF]

				C.-L. Tseng, M. Brimacombe, M. Xie, M. Rajan, H. Wang, J. Kolassa, S. Crystal, T.-C. Chen, L. Pogach, and M. Safford Seasonal Patterns in Monthly Hemoglobin A1c Values Am. J. Epidemiol., March 15, 2005; 161(6): 565 - 574. [Abstract] [Full Text] [PDF]

				R. R. Little, H. Vesper, C. L. Rohlfing, M. Ospina, S. Safar-Pour, and W. L. Roberts Validation by a Mass Spectrometric Reference Method of Use of Boronate Affinity Chromatography to Measure Glycohemoglobin in the Presence of Hemoglobin S and C Traits Clin. Chem., January 1, 2005; 51(1): 264 - 265. [Full Text] [PDF]

				N. Rifai, G. R. Cooper, W. V. Brown, W. Friedewald, R. J. Havel, G. L. Myers, and G. R. Warnick Clinical Chemistry Journal Has Contributed to Progress in Lipid and Lipoprotein Testing for Fifty Years Clin. Chem., October 1, 2004; 50(10): 1861 - 1870. [Full Text] [PDF]

				D. E. Goldstein, R. R. Little, R. A. Lorenz, J. I. Malone, D. Nathan, C. M. Peterson, and D. B. Sacks Tests of Glycemia in Diabetes Diabetes Care, July 1, 2004; 27(7): 1761 - 1773. [Full Text] [PDF]

				B. L Armor and M. L Britton Diabetes Mellitus Non-Glucose Monitoring: Point-of-Care Testing Ann. Pharmacother., June 1, 2004; 38(6): 1039 - 1047. [Abstract] [Full Text] [PDF]

				J L Camargo and J L Gross Conditions associated with very low values of glycohaemoglobin measured by an HPLC method J. Clin. Pathol., April 1, 2004; 57(4): 346 - 349. [Abstract] [Full Text] [PDF]

				W. Hoelzel, C. Weykamp, J.-O. Jeppsson, K. Miedema, J. R. Barr, I. Goodall, T. Hoshino, W. G. John, U. Kobold, R. Little, et al. IFCC Reference System for Measurement of Hemoglobin A1c in Human Blood and the National Standardization Schemes in the United States, Japan, and Sweden: A Method-Comparison Study Clin. Chem., January 1, 2004; 50(1): 166 - 174. [Abstract] [Full Text] [PDF]

				Tests of Glycemia in Diabetes Diabetes Care, January 1, 2004; 27(90001): s91 - 93. [Full Text] [PDF]

				D. B. Sacks Hemoglobin Variants and Hemoglobin A1c Analysis: Problem Solved? Clin. Chem., August 1, 2003; 49(8): 1245 - 1247. [Full Text] [PDF]

				S. S. Anand, F. Razak, V. Vuksan, H. C. Gerstein, K. Malmberg, Q. Yi, K. K. Teo, and S. Yusuf Diagnostic Strategies to Detect Glucose Intolerance in a Multiethnic Population Diabetes Care, February 1, 2003; 26(2): 290 - 296. [Abstract] [Full Text] [PDF]

				I. Sakurabayashi, T. Watano, S. Yonehara, K. Ishimaru, K. Hirai, T. Komori, and M. Yagi New Enzymatic Assay for Glycohemoglobin Clin. Chem., February 1, 2003; 49(2): 269 - 274. [Abstract] [Full Text] [PDF]

S. H. Saydah, D. Byrd-Holt, and M. I. Harris Projected Impact of Implementing the Results of the Diabetes Prevention Program in the U.S. Population Diabetes Care, November 1, 2002; 25(11): 1940 - 1945. [Abstract]