The national glycohemoglobin standardization program: a five-year progress report.

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.

MedDigital trends and tactics to lead into the future.

Physician executives need to harness appropriate digital technology by understanding key trends and implementing best tactics. Being and doing MedDigital means taking back control and improving care--and, at the same time, improving efficiencies and the bottom line. This article presents seven e-trends that are shaping health care: (1) Consumers and patients are pushing doctors to go digital; (2) from Web health information to MedDigital decision support; (3) beyond managed care to custom health; (4) wireless is the way of the new world; (5) Passive web portals yield to digital destinations; (6) e-commerce means lower transaction cost; and (7) develop e-health care ROI methodologies and track results. The authors provide myriad examples of new technology that will revolutionize health care and provide both physicians and consumers with valuable interactive tools to enhance health, treatment, and decision-making.

Use of GHb (HbA1c) in screening for undiagnosed diabetes in the U.S. population.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Disease and family contributors to adaptation in juvenile rheumatoid arthritis and juvenile diabetes.

OBJECTIVE: Research in the areas of pediatric rheumatology and pediatric chronic illness has emphasized comprehensive models of adaptation involving risk and resistance factors. This study examined adaptation, within this framework, among a large sample of children with chronic illness and children without chronic illness. METHODS: A comprehensive battery of adaptation measures was administered to a sample of 107 children with juvenile rheumatoid arthritis, 114 children with insulin-dependent diabetes mellitus, and 88 healthy controls. RESULTS: Medical diagnosis was associated with mothers' depression and a composite measure of parental (mother and father) distress and passive coping. Children's emotional and behavioral functioning was not related to medical diagnosis, but mothers' depression and parental distress were associated with child behavior problems. CONCLUSION: Because parental distress was associated with child functioning, interventions to ameliorate parental distress may have beneficial effects on the children's behavior and on parents' reactions to their children.

Trajectories of adaptation in pediatric chronic illness: the importance of the individual.

This study used individual growth modeling to examine individual difference and group difference models of adaptation. The adaptation of 27 children with juvenile rheumatoid arthritis (JRA) and 40 children with insulin-dependent diabetes mellitus (IDDM) was tracked for 18 months from diagnosis. A control group of 62 healthy children was followed over the same time period. Clustering procedures indicated that child and family adaptation could be described by a number of distinct adaptation trajectories, independent of diagnostic group membership. In contrast, parental adaptation trajectory was associated with diagnostic group membership and control over disease activity for the JRA group and with diagnostic group membership for healthy controls. The observation of common patterns across trajectory sets, as well as the finding that trajectories were differentially related to a number of variables of interest, support the use of trajectories to represent adaptation to chronic disease.

Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994.

OBJECTIVE: 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). RESEARCH DESIGN AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Monitoring glycemia in diabetes. Short-term assessment.

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.

Comparisons of studies on diabetic complications hampered by differences in GHb measurements.

OBJECTIVE: 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.) RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Is glycohemoglobin testing useful in diabetes mellitus? Lessons from the diabetes control and complications trial.

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.

Assessing anger expression in children and adolescents.

Anger expression styles are associated with psychological and physical well-being among adults. Little is known about the role of anger expression in children's functioning. This lack of knowledge has resulted, in part, from a lack of validated tools for anger expression measurement. The Pediatric Anger Expression Scale-3rd edition (PAES-III; Jacobs, Phelps, & Rohrs, 1989; Jacobs & Kronaizl, 1991) has been proposed as a reliable and valid assessment instrument of anger expression styles. The PAES-III includes three scales that measure anger turned inward, anger expressed outwardly, and anger controlled cognitively or behaviorally. We evaluated the psychometric properties of this instrument when it is administered verbally to children with juvenile rheumatoid arthritis, children with juvenile diabetes mellitus, and healthy children. Internal consistency was adequate for anger-in and anger-out, but marginal for anger-control. Concurrent validity was supported for the total sample. A principal components analysis suggested a four-factor model of anger expression. Overall, the PAES-III was found to have psychometric limitations. Use of a modified PAES-III may facilitate pediatric behavioral medicine research addressing risk factors for maladjustment among children with chronic illnesses.

Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases.

Islet cell Ag 512 (ICA512) is a recombinant human Ag that was isolated from an islet cDNA expression library by screening with human insulin-dependent diabetes mellitus sera. Specificity of reaction with diabetic sera was demonstrated initially by immunoprecipitation with a small number of diabetic and normal serum samples. To permit quantitative and rapid serum testing, ICA512 was purified and adapted to an ELISA format. In this way, a sensitivity of 48% with newly diagnosed diabetic sera has been measured with a panel of 80 sera. DNA sequencing of ICA512-3, a cDNA that contains a 1644 bp open reading frame, suggests that it codes for a transmembrane protein having a single membrane-spanning segment and a cytoplasmic domain that is closely related to the first intracellular (catalytic) domain of the T cell protein tyrosine phosphatase, CD45. Northern blot analysis of poly(A)+ RNAs from several human tissues indicates that ICA512 mRNA is expressed in brain and pancreas.

Glycated haemoglobin predicts progression to diabetes mellitus in Pima Indians with impaired glucose tolerance.

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.

Glycemic control and development of retinopathy in youth-onset insulin-dependent diabetes mellitus. Results of a 12-year longitudinal study.

BACKGROUND: In 1979, the authors began a prospective study of the natural history of retinopathy in youth-onset insulin-dependent diabetes mellitus (IDDM). Their major goal was to determine if there was an association between glycemic control and the development and progression of retinopathy. METHODS: The study consisted of 420 individuals with IDDM (onset younger than 20 years of age) and no retinopathy at baseline. Study subjects were enrolled between 1979 and 1988. Stereo color fundus photographs were obtained annually. Two eye endpoints were recorded: duration when retinopathy was first detected, and when proliferative retinopathy was detected. Glycemic control was assessed by quarterly determinations of glycohemoglobin (GHb). Life-table analyses were performed relating duration of diabetes, sex, GHb, and age of diabetes onset to development of retinopathy. RESULTS: Retinopathy did not develop before 2 years' duration or before puberty. The prevalence of retinopathy was 50% by 9 years' duration and 100% by 20 years' duration. Retinopathy developed in females approximately 2 years sooner than in males, but plotting duration as postpubertal years resulted in nearly identical rates. Retinopathy developed significantly earlier in subjects with prepubertal onset of diabetes than in subjects with postpubertal onset if duration was plotted as postpubertal years. When separated into three groups based on GHb levels (< 7.5%, 7.5%-9%, > 9%), retinopathy developed approximately 2 years later in subjects in the less than 7.5% GHb group than those in the higher GHb groups. Proliferative retinopathy developed in 11 subjects. Their mean GHb level was higher than the mean GHb for those without proliferative retinopathy (10.9 versus 8.6%; P < 0.01). The higher the level of GHb, the sooner proliferative changes were detected. CONCLUSION: Long-term glycemic control is significantly related to both development and progression of retinopathy. Prepubertal duration of diabetes is a significant risk factor for the development of retinopathy.