Performance of recommended screening tests for undiagnosed diabetes and dysglycemia.

OBJECTIVE: To evaluate the performance, in settings typical of opportunistic and community screening programs, of screening tests currently recommended by the American Diabetes Association (ADA) for detecting undiagnosed diabetes. RESEARCH DESIGN AND METHODS: Volunteers aged > or =20 years without previously diagnosed diabetes (n = 1,471) completed a brief questionnaire and underwent recording of postprandial time and measurement of capillary blood glucose (CBG) with a portable sensor. Participants subsequently underwent a 75-g oral glucose tolerance test; fasting serum glucose (FSG) and 2-h postload serum glucose (2-h SG) concentrations were measured. The screening tests we studied included the ADA risk assessment questionnaire, the recommended CBG cut point of 140 mg/dl, and an alternative CBG cut point of 120 mg/dl. Each screening test was evaluated against several diagnostic criteria for diabetes (FSG > or =126 mg/dl, 2-h SG > or =200 mg/dl, or either) and dysglycemia (FSG > or =110 mg/dl, 2-h SG > or =140 mg/dl, or either). RESULTS: Among all participants, 10.7% had undiagnosed diabetes (FSG > or =126 or 2-h SG > or =200 mg/dl), 52.1% had a positive result on the questionnaire, 9.5% had CBG > or =140 mg/dl, and 18.4% had CBG > or =120 mg/dl. The questionnaire was 72-78% sensitive and 50-51% specific for the three diabetes diagnostic criteria; CBG > or =140 mg/dl was 56-65% sensitive and 95-96% specific, and CBG > or =120 mg/dl was 75-84% sensitive and 86-90% specific. CBG > or =120 mg/dl was 44-62% sensitive and 89-90% specific for dysglycemia. CONCLUSIONS: Low specificity may limit the usefulness of the ADA questionnaire. Lowering the cut point for a casual CBG test (e.g., to 120 mg/dl) may improve sensitivity and still provide adequate specificity.     

三种红细胞不规则抗体筛选试验方法的比较

目的 寻找简便、快速、敏感的红细胞不规则抗体筛选的试验方法。方法 采用蛋白水解酶法、抗球蛋白法（AGT）及聚凝胺三步法试验（TSPT）平行检测一批Rh、MNSs、Duffy、Kidd等系统的不规则抗体效价,观察TSPT等的敏感性。结果 在上述3种方法中,TSPT敏感性最高,其次为AGT,TSPT测出了所有IsG和IgM性质的不规则抗体,酶技术未检出抗-M、N、S、s、Fy^a、Fy^b,TSPT和AGT的试剂性能稳定。结论 TSPT操作简便迅速,敏感性高,无需特殊设备,TSPT适用于红细胞血型不规则抗体筛选的常规试验。     

三种红细胞不规则抗体筛选试验方法的比较

目的寻找简便、快速、敏感的红细胞不规则抗体筛选的试验方法。方法采用蛋白水解酶法、抗球蛋白法(AGT)及聚凝胺三步法试验(TSPT)平行检测一批Rh、MNSs、Duffy、K idd等系统的不规则抗体效价,观察TSPT等的敏感性。结果在上述3种方法中,TSPT敏感性最高,其次为AGT,TSPT测出了所有IgG和IgM性质的不规则抗体,酶技术未检出抗-M、N、S、s、Fya、Fyb,TSPT和AGT的试剂性能稳定。结论TSPT操作简便迅速,敏感性高,无需特殊设备,TSPT适用于红细胞血型不规则抗体筛选的常规试验。     

Deriving ethnic-specific BMI cutoff points for assessing diabetes risk

OBJECTIVE

The definition of obesity (BMI ≥30 kg/m²), a key risk factor of diabetes, is widely used in white populations; however, its appropriateness in nonwhite populations has been questioned. We compared the incidence rates of diabetes across white, South Asian, Chinese, and black populations and identified equivalent ethnic-specific BMI cutoff values for assessing diabetes risk.

RESEARCH DESIGN AND METHODS

We conducted a multiethnic cohort study of 59,824 nondiabetic adults aged ≥30 years living in Ontario, Canada. Subjects were identified from Statistics Canada’s population health surveys and followed for up to 12.8 years for diabetes incidence using record linkages to multiple health administrative databases.

RESULTS

The median duration of follow-up was 6 years. After adjusting for age, sex, sociodemographic characteristics, and BMI, the risk of diabetes was significantly higher among South Asian (hazard ratio 3.40, P < 0.001), black (1.99, P < 0.001), and Chinese (1.87, P = 0.002) subjects than among white subjects. The median age at diagnosis was lowest among South Asian (aged 49 years) subjects, followed by Chinese (aged 55 years), black (aged 57 years), and white (aged 58 years) subjects. For the equivalent incidence rate of diabetes at a BMI of 30 kg/m² in white subjects, the BMI cutoff value was 24 kg/m² in South Asian, 25 kg/m² in Chinese, and 26 kg/m² in black subjects.

CONCLUSIONS

South Asian, Chinese, and black subjects developed diabetes at a higher rate, at an earlier age, and at lower ranges of BMI than their white counterparts. Our findings highlight the need for designing ethnically tailored prevention strategies and for lowering current targets for ideal body weight for nonwhite populations.Type 2 diabetes is a growing epidemic. There currently are an estimated 285 million people with known type 2 diabetes (henceforth “diabetes”) worldwide; this number is projected to rise to ~438 million by 2030, with a disproportionate burden expected in developing countries, particularly India and China, and among ethnic minorities living in wealthier nations (1). Earlier cross-sectional studies (2–4) have reported ethnic differences in the prevalence of diabetes; however, to date there have been no longitudinal studies comparing the incidence rate and age at diagnosis of diabetes across the world’s four major ethnic groups (white, South Asian, Chinese, and black populations) and among individuals from these four groups living in the same social macroenvironment.Although the definition of obesity (BMI ≥30 kg/m²), a key risk factor of diabetes, has been validated in white populations (5), its appropriateness in Asian populations has been questioned (6). Recognizing this, a World Health Organization (WHO) expert panel was convened in 2002 to discuss the potential for developing Asian-specific BMI cutoff points for obesity (7). The consultation concluded that with the data available at the time, there was no clear BMI cutoff point that would be universally applicable to Asians and that the prespecified BMI ranges would be retained (i.e., underweight <18.5 kg/m², normal 18.5 to <25 kg/m², overweight 25 to <30 kg/m², and obese ≥30 kg/m²) for assessing the risk of obesity-related chronic diseases. Nevertheless, the WHO expert panel recommended potential BMI categories for public health action in people of Asian descent (i.e., underweight <18.5 kg/m², increasing but acceptable risk 18.5 to <23 kg/m², increased risk 23 to <27.5 kg/m², and high risk ≥27.5 kg/m²) (7). The WHO panel also emphasized the need for longitudinal studies using disease outcomes data to better understand the relationship between BMI and obesity-related diseases and to derive and validate ethnic-specific BMI cutoff points. Because of these recommendations, several studies have attempted to redefine obesity for Asians. A systematic review (8) of these studies found that, although most studies were in favor of lowering the BMI cutoff point for obesity in Asians, the majority of these studies used cross-sectional data and some did not report health outcomes.The two main objectives of this multiethnic cohort study were 1) to compare the incidence and age at diagnosis of diabetes across white, South Asian, Chinese, and black subjects living in Ontario, Canada, one of the world’s most ethnically diverse regions; and 2) to derive ethnically appropriate population-based BMI cutoff values for obesity in assessing diabetes risk using clinically ascertained diabetes. A cutoff point of a BMI of 30 kg/m² was chosen because it represents the current standard for obesity, a key risk factor of diabetes.     

Evaluation of three potential screening tests for diabetes mellitus in a biethnic population

We tested the ability of three potential screening tests for diabetes (fasting plasma glucose value greater than or equal to 140 mg/dl, 1-h postglucose (PG) load value greater than or equal to 200 mg/dl, and 2-h PG value greater than or equal to 200 mg/dl) to detect non-insulin-dependent diabetes in 130 diabetic Mexican Americans (MAs) and 50 diabetic Anglo Americans (AA) using the National Diabetes Data Group criteria as the standard. The sensitivity of the fasting plasma glucose (FPG) cutpoint in detecting diabetes was low in both AAs (36.0%) and MAs (59.3%) and was related to the age-adjusted prevalence rates of diabetes in the two ethnic groups (AAs, 4.9%; MAs, 10.9%). The 2-h PG load cutpoint had good sensitivity (greater than 93%) and specificity (greater than 99%) in both ethnic groups. The ethnic difference in the sensitivity of the FPG cutpoint appeared to be related to the greater hyperglycemia of diabetic MAs compared with diabetic AAs. Nearly 30% of diabetic MAs had FPG values greater than or equal to 200 mg/dl as contrasted with only 10% of diabetic AAs. The difference in severity of hyperglycemia between the ethnic groups appears to be unrelated to ethnic differences in adiposity, pharmacologic treatment, or delay in diagnosis, although longer disease duration in MAs may explain part of the difference.     

血液感染性疾病标志物筛检中应重视的若干问题

血液筛查质量的高低，直接关系到受血者的安全。目前，国内采供血机构针对感染性疾病病原体筛检的标志物共有4种，即乙型肝炎病毒表面抗原(HBsAg)、丙型肝炎病毒抗体(抗HCV)、人免疫缺陷病毒抗体(抗HIV)和梅毒抗体。主要采用酶联免疫吸附试验(ELISA)方法检测，方法模式有一步双抗体夹心法、间接法和一步或两步双抗原夹心法等。     

成人糖尿病3种自身抗体检测的临床分析

目的 分析探讨谷氨酸脱羧酶抗体（GAD—Ab）、胰岛细胞抗体（ICA）、胰岛素抗体（IAA）的检测对成人糖尿病的诊断价值和选择治疗方案的指导意义。方法 定性酶联免疫吸附试验（ELISA）检测自身抗体，放免法检测胰岛素和C-肽。结果 468例成人糖尿病患者GAD—Ab阳性130例，阳性率27．8％，ICA阳性共89例，阳性率19．0％，IAA的阳性144例，阳性率30．8％，GAD—Ab、IAA、ICA三者同时阳性14例，阳性率3．1％．分别随机抽查了GAD—Ab或ICA阳性和3种抗体阴性各50例患者的空腹及给予100克葡萄糖2小时后的胰岛素和C-肽含量，比较差异无显著性意义，P〉0．05。结论 成人糖尿患者及时检测GAD-Ab、IAA、ICA对临床糖尿病的分型和治疗方案选择有重要意义。     

Costs of screening for pre-diabetes among US adults: a comparison of different screening strategies

OBJECTIVE: We evaluated various strategies to identify individuals aged 45-74 years with pre-diabetes (either impaired glucose tolerance or impaired fasting glucose). RESEARCH DESIGN AND METHODS: We conducted a cost analysis to evaluate the effectiveness (proportion of cases identified), total costs, and efficiency (cost per case identified) of five detection strategies: an oral glucose tolerance test (OGTT), a fasting plasma glucose (FPG) test, an HbA(1c) test, a capillary blood glucose (CBG) test, and a risk assessment questionnaire. For the first strategy, all individuals received an OGTT. For the last four strategies, only those with a positive screening test received an OGTT. Data were from the Third U.S. National Health and Nutrition Examination Survey, 2000 census, Medicare, and published literature. One-time screening costs were estimated from both a single-payer perspective and a societal perspective. RESULTS: The proportion of pre-diabetes and undiagnosed diabetes identified ranged from 69% to 100% (12.1-17.5 million). The cost per case identified ranged from US dollars 176 to US dollars 236 from a single-payer perspective and from US dollars 247 to US dollars 332 from a societal perspective. Testing all with OGTT was the most effective strategy, but the CBG test and risk assessment questionnaire were the most efficient. If people are substantially less willing to take an OGTT than a FPG test, then the FPG testing strategy was the most effective strategy. CONCLUSIONS: There is a tradeoff between effectiveness and efficiency in choosing a strategy. The most favorable strategy depends on if the goal of the screening program is to identify more cases or to pursue the lowest cost per case. The expected percentage of the population willing to take an OGTT is also a consideration.     

Simple screening tests for peripheral neuropathy in the diabetes clinic

OBJECTIVE: The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy. RESEARCH DESIGN AND METHODS: We assessed four simple tests (the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test. RESULTS: The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34, and 0.50, respectively The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring approximately 60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test. CONCLUSIONS: Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.     

An economic analysis of interventions for diabetes

The objective of this article is to stratify interventions for diabetes according to their economic impact. We conducted a review of the literature to select articles that performed a cost-benefit analysis for 17 widely practiced interventions for diabetes. A scale for categorizing interventions according to their economic impact was defined. The 17 interventions were classified as follows: 1) clearly cost-saving, 2) clearly cost-effective, 3) possibly cost-effective, 4) non-cost-effective, or 5) unclear. Clearly cost-saving interventions included eye care and pre-conception care. Clearly cost-effective interventions included nephropathy prevention in type 1 diabetes and improved glycemic control. Possibly cost-effective interventions included nephropathy prevention in type 2 diabetes and self-management training. Non-cost-effective interventions were not identified. Interventions with unclear economic impact included case management, medical nutrition therapy, self-monitoring of blood glucose, foot care, blood pressure control, blood lipid control, smoking cessation, exercise, weight loss, HbA1c measurement, influenza vaccination, and pneumococcus vaccination. Widely practiced interventions for patients with diabetes can be clearly cost-saving and clearly cost-effective. These practices are attractive from both a medical and an economic perspective.     

A comparison of three stool tests for colorectal cancer screening.

The annual guaiac or immunochemical fecal occult blood test (FOBT) is one of the five colorectal cancer (CRC) screening regimens recommended by the American Cancer Society (Smith, Cokkinides, & Eyre, 2005). Stool-based deoxyribonucleic acid (DNA) testing for CRC is considered a promising technology (Smith, Cokkinides, & Eyre, 2003). Numerous features of three noninvasive stool tests for CRC are compared.     

Diagnostic efficiency of different amphetamine screening tests--the search for an optimal cutoff.

Increased use of designer drugs (amphetamines and amphetamine-like substances) raises the need for fast screening tests in urine in clinical settings, workplace and drug rehabilitation. Immunological assays currently used are subject to unwanted crossreactivities, partly depending on the cutoff concentrations used. The values recommended in Europe and the USA are 500 and 1000 ng/ml, respectively. In Switzerland, the recommended concentration of 300 ng/ml results in a high rate of false-positive urine samples and expensive, time-consuming confirmation testing. Using the Abbott Axsym analyzer, we found numerous false positives from patients in rehabilitation centers due to concomitant medication. Therefore, the diagnostic sensitivity and specificity of the Abbott test at different cutoff concentrations and the sensitivity of the Roche Cobas Integra, Beckman Synchron and Biosite Triage point-of-care test were examined. HPLC BioRad Remedi was chosen as the method of higher hierarchical order. The specificity of the Axsym analyzer (300 ng/ml) was 86%. At 500 ng/ml or 1000 ng/ml the specificity was increased to 99 or 100%, respectively, while the sensitivity only decreased from 97 to 91 or 81%, respectively. In summary, the cutoff concentration for amphetamine screening tests should not be below 500 ng/ml to avoid a high rate of false-positive results.     

Gestational diabetes mellitus screening tests: a review of current recommendations.

Early recognition and management of gestational diabetes decreases the incidence of macrosomia. Infant morbidity and mortality are also decreased. While there continues to be little agreement regarding precise methods of screening and diagnostic criteria for GDM, most specialists recommend screening with the 50-g oral glucose load followed by a 3-hour GTT. Screening only those women with select risk factors may result in 30% to 50% of women with gestational diabetes being overlooked. Careful explanation of testing methods and implications may result in improved patient understanding of the importance of this diagnosis and of its impact on future health care needs.     

Implementation of newborn screening for Krabbe disease: Population study and cutoff determination

Objective

The aim of this study was to develop a newborn screening algorithm for Krabbe disease.

Design and methods

We measured the galactocerebrosidase activity of 139,074 anonymous newborns, 56 known carriers, and 16 Krabbe patients using a tandem mass spectrometry method. The activities were converted to percentages of daily mean activity (%DMA), and the results from diseased and normal populations were used to establish cutoffs.

Results

The absolute activities for the newborns ranged from 0.17 to 355 μmol/L h (N = 139,074) and activities for Krabbe-positive controls ranged from 0.08 to 0.48 μmol/L h (N = 16, n = 91 measurements) while activities for carriers ranged from 0.28 to 2.71 μmol/L h (N = 56, n = 72 measurements). Cutoffs were set based on results from Krabbe-positive and carrier controls and the newborn population distribution.

Conclusions

The algorithm and cutoffs we propose provided 100% detection of all positive controls with 60/100,000 screen positive results predicted. In the course of this study, one anonymous newborn was predicted to have Krabbe disease based on enzyme activity and subsequent DNA analysis.     

A comparison of three psychiatric screening tests using receiver operating characteristic (ROC) analysis

Self-administered screening questionnaires are available to assist primary care physicians in detecting undiagnosed depression and anxiety disorders. This study used receiver operating characteristic (ROC) analysis to evaluate three such tests: the General Health Questionnaire (GHQ), the Mental Health Inventory (MHI), and the Somatic Symptom Inventory (SSI). Stratified by the results of a preliminary GHQ, 364 health maintenance organization (HMO) members were given these tests and a Diagnostic Interview Schedule (DIS), the latter used as a "truth" standard for current psychiatric diagnosis. The MHI performed significantly better than the GHQ in detecting mental disorders generally and anxiety disorders in particular, and somewhat better in detecting affective disorders. The SSI performed best in detecting anxiety disorders and was significantly better than the GHQ. When subjects who had participated in a previous study involving repeated GHQ administration were excluded, sensitivity of all tests improved, especially the GHQ. We conclude that the MHI can be a useful tool for screening primary care patients, and that the SSI has additional predictive value with respect to anxiety disorders.     

Use of the diabetes risk score for opportunistic screening of undiagnosed diabetes and impaired glucose tolerance: the IGLOO (Impaired Glucose Tolerance and Long-Term Outcomes Observational) study

OBJECTIVE: To evaluate an opportunistic screening strategy addressed to individuals with one or more cardiovascular risk factor, based on the Diabetes Risk Score (DRS) as the initial instrument, for the identification of individuals with type 2 diabetes or impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: The DRS, a simple self-administered questionnaire, was completed by individuals identified by general practitioners and presenting with one or more cardiovascular risk factor. All patients underwent a 2-h oral glucose tolerance test (OGTT). The optimal DRS cutoff was calculated by applying the receiver-operating characteristic curve. RESULTS: Overall, 1,377 individuals aged between 55 and 75 years received an OGTT and completed the DRS. Mean DRS values showed a marked variation according to glucose metabolism categories, as follows: 8.7 +/- 3.0 in normoglycemic individuals, 9.5 +/- 3.1 in individuals with impaired fasting glucose, 9.9 +/- 3.3 in individuals with IGT, and 12.0 +/- 3.5 in individuals with type 2 diabetes. The receiver-operating characteristic curve showed that, with a cutoff of 9, the sensitivity of DRS in detecting individuals with glucose abnormalities (type 2 diabetes or IGT) was 77% and the specificity 45%. The use of the DRS as an initial screening instrument, followed by the measurement of fasting blood glucose in individuals with a score > or =9 and by the OGTT in individuals with a fasting blood glucose between 5.6 and 6.9 mmol/l, would lead to the identification of 83% of the case subjects with type 2 diabetes and 57% of the case subjects with IGT, at a cost of an OGTT in 38% of the sample and a fasting blood glucose in 64%. CONCLUSIONS: The DRS can represent a valid inexpensive instrument for opportunistic screening and a useful alternative to indiscriminate fasting blood glucose measurement, not readily available in general practice.