[Show abstract][Hide abstract] ABSTRACT: C-peptide measurement has been widely used as a marker of insulin secretion in patients with diabetes. We assessed the comparability of C-peptide results obtained with different methods and by different laboratories and determined whether C-peptide results could be harmonized by normalization with a WHO reference reagent or with plasma.
We sent 16 different heparin plasma samples to 15 laboratories in 7 countries. The samples were analyzed with 10 different assay methods. A WHO C-peptide standard was also sent to each laboratory and used to determine the feasibility of normalizing results. To assess the impact of calibrator matrix on the comparability of results, we also used the mean results of all laboratories for 4 of the samples to normalize the remaining sample results.
Between-laboratory variability increased with increasing C-peptide concentrations. Normalization of results with WHO reference reagents did not improve comparability, but normalization with samples significantly improved comparability among laboratories and methods. The 95% confidence interval estimate for the SD for the lab/method effect (0.0-0.061) using sample-normalized values did not overlap with the 95% CI estimate with the raw data (0.090-0.225).
C-peptide results generated by different methods and different laboratories do not always agree, especially at higher concentrations of C-peptide. These data support the concept of using a single laboratory for multisite studies and support efforts to harmonize C-peptide measurements by use of calibrators prepared in the sample matrix.
[Show abstract][Hide abstract] ABSTRACT: Clinical trials require assays that provide consistent results during the course of a study. The hemoglobin A1c (HbA1c) assay, a measure of chronic glycemia, is critical to the study of diabetes control and complications.
The Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), required 20 years of consistent HbA1c results, measured by three different ion-exchange HPLC procedures. To maintain and document consistent HbA1c results measured in the DCCT and EDIC Central Biochemistry Laboratory, a backup laboratory used frozen hemolysates as long-term calibrators and a HPLC method with a single lot of Bio-Rex 70 resin.
Over 20 years, long-term quality-control values have remained constant. Four studies of nondiabetic ranges produced nearly identical values [mean (SD), 5.1 (0.5)%, 4.9 (0.3)%, 5.0 (0.4)%, and 5.0 (0.3)%].
The overall consistency of the HbA1c assays during the 20-year course of the DCCT and EDIC has been critical in establishing the benefits of intensive therapy and in understanding the relationship between long-term glycemia and the development and progression of the complications of diabetes.
[Show abstract][Hide abstract] ABSTRACT: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.
An expert committee drafted evidence-based recommendations for the use of laboratory analysis in patients with diabetes. An external panel of experts reviewed a draft of the guidelines, which were modified in response to the reviewers' suggestions. A revised draft was posted on the Internet and was presented at the AACC Annual Meeting in July, 2000. The recommendations were modified again in response to oral and written comments. The guidelines were reviewed by the Professional Practice Committee of the American Diabetes Association.
Measurement of plasma glucose remains the sole diagnostic criterion for diabetes. Monitoring of glycemic control is performed by the patients, who measure their own plasma or blood glucose with meters, and by laboratory analysis of glycated hemoglobin. The potential roles of noninvasive glucose monitoring, genetic testing, autoantibodies, microalbumin, proinsulin, C-peptide, and other analytes are addressed.
The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are of minimal clinical value at the present time, and measurement of them is not recommended.
[Show abstract][Hide abstract] ABSTRACT: To define the relationship between HbA(1c) and plasma glucose (PG) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial (DCCT).
The DCCT was a multicenter, randomized clinical trial designed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes. Quarterly HbA(1c) and corresponding seven-point capillary blood glucose profiles (premeal, postmeal, and bedtime) obtained in the DCCT were analyzed to define the relationship between HbA(1c) and PG. Only data from complete profiles with corresponding HbA(1c) were used (n = 26,056). Of the 1,441 subjects who participated in the study, 2 were excluded due to missing data. Mean plasma glucose (MPG) was estimated by multiplying capillary blood glucose by 1.11. Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA(1c).
Linear regression analysis, using MPG and HbA(1c) summarized by patient (n = 1,439), produced a relationship of MPG (mmol/l) = (1.98 . HbA(1c)) - 4.29 or MPG (mg/dl) = (35.6 . HbA(1c)) - 77.3, r = 0.82). Among individual time points, afternoon and evening PG (postlunch, predinner, postdinner, and bedtime) showed higher correlations with HbA(1c) than the morning time points (prebreakfast, postbreakfast, and prelunch).
We have defined the relationship between HbA(1c) and PG as assessed in the DCCT. Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA(1c) goals.
Diabetes Care 03/2002; 25(2):275-8. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the use of GHb as a screening test for undiagnosed diabetes (fasting plasma glucose > or =7.0 mmol/l) in a representative sample of the U.S. population.
The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged > or =20 years. Of these subjects, 7,832 participated in a morning examination session, of which 1,273 were excluded because of a previous diagnosis of diabetes, missing data, or fasting time of <8 h before examination. Venous blood was obtained to measure fasting plasma glucose and GHb in the remaining 6,559 subjects. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of GHb for detecting diabetes at increasing GHb cutoff levels.
GHb demonstrated high sensitivity (83.4%) and specificity (84.4%) for detecting undiagnosed diabetes at a GHb cutoff of 1 SD above the normal mean. Moderate sensitivity (63.2%) and very high specificity (97.4%) were evident at a GHb cutoff of 2 SD above the normal mean. Sensitivity at this level ranged from 58.6% in the non-Hispanic white population to 83.6% in the Mexican-American population; specificity ranged from 93.0% in the nonHispanic black population to 98.3% in the non-Hispanic white population.
GHb is a highly specific and convenient alternative to fasting plasma glucose for diabetes screening. A GHb value of 2 SD above the normal mean could identify a high proportion of individuals with undiagnosed diabetes who are at risk for developing diabetes complications.
Diabetes Care 02/2000; 23(2):187-91. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the prevalence and time trends for diagnosed and undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults by age, sex, and race or ethnic group, based on data from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) and prior Health and Nutrition Examination Surveys (HANESs).
NHANES III contained a probability sample of 18,825 U.S. adults > or = 20 years of age who were interviewed to ascertain a medical history of diagnosed diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were obtained, and a subsample of 2,844 adults between 40 and 74 years of age who received an oral glucose tolerance test. The Second National Health and Nutrition Examination Survey, 1976-1980, and Hispanic HANES used similar procedures to ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes Association fasting plasma glucose criteria and the 1980-1985 World Health Organization (WHO) oral glucose tolerance test criteria.
Prevalence of diagnosed diabetes in 1988-1994 was estimated to be 5.1% for U.S. adults > or = 20 years of age (10.2 million people when extrapolated to the 1997 U.S. population). Using American Diabetes Association criteria, the prevalence of undiagnosed diabetes (fasting plasma glucose > or = 126 mg/dl) was 2.7% (5.4 million), and the prevalence of impaired fasting glucose (110 to < 126 mg/dl) was 6.9% (13.4 million). There were similar rates of diabetes for men and women, but the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times the rate for non-Hispanic whites. Based on American Diabetes Association criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total population of people who were 40-74 years of age increased from 8.9% in the period 1976-1980 to 12.3% by 1988-1994. A similar increase was found when WHO criteria were applied (11.4 and 14.3%).
The high rates of abnormal fasting and postchallenge glucose found in NHANES III, together with the increasing frequency of obesity and sedentary lifestyles in the population, make it likely that diabetes will continue to be a major health problem in the U.S.
Diabetes Care 04/1998; 21(4):518-24. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The monitoring of glycemic status is considered a cornerstone of diabetes care. This article reviews current recommendations for routine glycemia monitoring, with emphasis on practical applications. A description of the newly developed National Glycohemoglobin Standardization Program also is provided.
Endocrinology & Metabolism Clinics of North America 10/1997; 26(3):475-86. · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare glycated hemoglobin (GHb) values of the relationship between glycemic control and complications of diabetes from laboratories involved in long-term studies (Steno, Oslo, Stockholm, Diabetes Control and Complications Trial, and Linköping.)
Blood samples were collected from 25 subjects selected to represent the clinically relevant measurement range. Fresh whole-blood samples were distributed and analyzed within 4 days of sample collection. Pretreatment of samples and analyses of GHb were performed according to the routine method of each study's central or reference laboratory. Results from each laboratory were compared with the group mean, i.e., the mean of all results for each sample.
Regression analyses with the group mean values as independent variables and results from each laboratory as dependent variables showed that Oslo's result had a slope significantly different from the group mean. Laboratories used by the DCCT, Oslo, and Steno studies gave, on average, 0.4, 0.4, and 0.7% higher HbA1c readings than the group mean, respectively, while HbA1c results from Linköping and Stockholm were, on average, 0.6 and 1.0% lower, respectively.
There were large differences in GHb values among laboratories participating in studies of diabetic complications. The present data offer a guide to the comparison of results from the studies and underscores the need for standardization of GHb measurements.
Diabetes Care 08/1996; 19(7):726-9. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To address the question, Do laboratory tests cost money or save money? we have used as a model for discussion a common chronic disease, diabetes mellitus, and a widely used laboratory test, that for glycohemoglobin, a measure of long-term glycemia used to manage diabetic patients. Diabetes mellitus is serious, highly prevalent, and costly. In 1992, $1 of every $7 spent on health in the US was for diabetes, predominantly for treatment of the chronic complications of the disease. The recently completed Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are related to the degree of altered glycemia as quantified by determinations of glycohemoglobin. Thus, use of glycohemoglobin testing for routine diabetes care provides an objective measure of a patient's risk for developing diabetic complications. Results of this test can alert patients and health providers to the need for change in the treatment plan. Optimal use of glycohemoglobin testing for diabetes care will require standardization of test results.
[Show abstract][Hide abstract] ABSTRACT: Glycated haemoglobin could offer several practical advantages over the OGTT for assessing glucose metabolism. Initial cross-sectional studies (1983-1985) on 381 subjects (mostly Pima Indians) described the relationship between HbA1c (a specific glycated Hb) and the OGTT. We performed follow-up OGTTs and HbA1c measurements on 257 of these same subjects 1.6-6.1 years later. Subjects were again grouped according to both the result of the OGTT (normal, IGT or diabetes, by WHO criteria) and HbA1c result (normal or elevated based on mean +/- 1.96 SD of normal). Of 66 subjects with IGT at baseline, 47 (71%) had normal HbA1c and 19 (29%) had elevated HbA1c. Twenty-six (39%) of these subjects had diabetes at follow-up. Of these subjects with IGT, a significantly greater percentage of subjects with elevated HbA1c at baseline (68%) showed worsening to diabetes than those with a normal HbA1c (28%); (chi-square = 7.8, df = 1, p < 0.01). Thus, in subjects with IGT, glycated Hb may be a useful predictor of progression to diabetes.