糖化血红蛋白用于筛查糖尿病的意义

目的比较并评价空腹血糖（FPG）和糖化血红蛋白（HbA1c）在筛查DM中的应用价值。方法上海地区研究对象2298名,为明确DM诊断而就诊者和DM高危人群接受DM筛查者,男956名,女1342名,年龄52±13岁,行OGTT并测定HbA1C;以其工作特征曲线（ROC）评价FPG和HbA。C在筛查DM中的敏感性和特异性。结果（1）按照1999年WHO的DM诊断标准,本研究人群糖耐量正常（NGT）、空腹血糖受损（IFG）、糖耐量受损（IGT）、IGT合并IFG和DM者分别为830、110、380、183、795例。其中DM患病率为34．6％。（2）依据ROC判断,与DM状态相关的FPG最佳临界点为6．1mmol／L,敏感性和特异性均为81．5％,曲线下面积为0．899（95％CI0．885～0．914）,阳性似然比4．18,阴性似然比0．23;与DM状态相关的HbA1c最佳临界点为6．1％,敏感性和特异性均为81．0％,曲线下面积为0．890（95％CI0．876-0．904）,阳性似然比4．26,阴性似然比0．23;如应用FPG≥6．1mmol／L或HbA1c≥6．1％筛查DM,敏感性和特异性分别为96．5％和65．2％,阳性似然比2．77,阴性似然比0．05。结论FPG和HbA1C在筛查DM中具有相似的价值,二者均有相似的特异性和敏感性以及阳性似然比和阴性似然比。为了最大限度的筛查出DM患者,建议对于6．1mmol／L≤FPG〈7．0mmol／L或HbA1c≥6．1％的患者行OGTT检查以明确有无DM。     

HbA(1c) as a screening tool for detection of Type 2 diabetes: a systematic review.

AIM: To assess the validity of glycated haemoglobin A(1c) (HbA(1c)) as a screening tool for early detection of Type 2 diabetes. METHODS: Systematic review of primary cross-sectional studies of the accuracy of HbA(1c) for the detection of Type 2 diabetes using the oral glucose tolerance test as the reference standard and fasting plasma glucose as a comparison. RESULTS Nine studies met the inclusion criteria. At certain cut-off points, HbA(1c) has slightly lower sensitivity than fasting plasma glucose (FPG) in detecting diabetes, but slightly higher specificity. For HbA(1c) at a Diabetes Control and Complications Trial and UK Prospective Diabetes Study comparable cut-off point of > or = 6.1%, the sensitivity ranged from 78 to 81% and specificity 79 to 84%. For FPG at a cut-off point of > or = 6.1 mmol/l, the sensitivity ranged from 48 to 64% and specificity from 94 to 98%. Both HbA(1c) and FPG have low sensitivity for the detection of impaired glucose tolerance (around 50%). CONCLUSIONS HbA(1c) and FPG are equally effective screening tools for the detection of Type 2 diabetes. The HbA(1c) cut-off point of > 6.1% was the recommended optimum cut-off point for HbA(1c) in most reviewed studies; however, there is an argument for population-specific cut-off points as optimum cut-offs vary by ethnic group, age, gender and population prevalence of diabetes. Previous studies have demonstrated that HbA(1c) has less intra-individual variation and better predicts both micro- and macrovascular complications. Although the current cost of HbA(1c) is higher than FPG, the additional benefits in predicting costly preventable clinical complications may make this a cost-effective choice.     

糖化血红蛋白对中国人群糖尿病诊断价值的Meta分析

 目的 系统评价糖化血红蛋白(HbA1c)≥6.5%在中国成人糖尿病诊断中的价值。 
方法 计算机检索国内外重要数据库,搜索有关HbA1c≥6.5%在中国成人中糖尿病诊断价值的文献。采用诊断性试验准确性质量评价工具（QUADAS）评价纳入文献质量,应用Meta-Disc1.4软件对纳入研究进行综合定量评价,并绘制综合ROC（SROC）曲线。
结果 共纳入11篇文献。对于HbA1c≥6.5%在中国成人中的诊断价值为：合并敏感度为0.62(95%CI：0.60~0.64),合并特异度为0.96(95%CI：0.95~0.96),诊断性比值比(DOR)为40.25(95%CI：20.79~77.95),AUC_SROC为0.7702(s_x=0.0636),Q=0.7103(s_x=0.0537)。
结论 HbA1c≥6.5%在中国成人糖尿病中的诊断特异度非常高,但敏感度相对较低,存在一定的漏诊率,需结合血糖检测以降低漏诊率。     

酶法测定HbA1c浓度的临床应用

目的 探讨酶法测定HbA1c浓度的临床应用价值.方法 根据定值高低值质控物的检测结果来评价酶法测定HbA1c的稳定性,用酶法测定31例糖尿病患者、68例非糖尿病对照者的HbA1c浓度,将结果与高效液相色谱(HPLC)法测得的结果进行比较和分析.结果 酶法的批内CV为0.93% (低值)、0.55%(高值),批间CV为1.43% (低值)、1.03%(高值);与HPLC法相关性系数r分别为0.967(n=31,P<0.01)、0.954(n=68,P<0.01).结论 酶法测定HbA1c可在全自动生化分析仪上进行,且具有简便、快速、易于推广等优点.     

空腹血糖和糖化血红蛋白用于筛查糖尿病的研究

目的评估空腹血糖(FPG)和糖化血红蛋白(HbA1c)在筛查糖尿病(DM)和糖耐量受损(IGT)中的应用价值。方法北京地区研究对象1118名,为明确DM诊断而就诊者和DM高危人群接受DM筛查者,男489名,女629名,平均48±12岁,行口服葡萄糖耐量试验(OGTT)并测定HbA1c。结果按照1999年WHO的DM诊断标准,本研究人群糖耐量正常(NGT)、空腹血糖受损(IFG)、IGT、IGT合并IFG和DM者分别为510、35、155、52、366例。采用受试者工作特征曲线(ROC曲线)判断,与以OGTT诊断的DM状态相关的FPG临界点为6.2mmol/L,敏感性和特异性分别为85.0%和90.4%,曲线下面积0.943(95%CI0.927～0.959),阳性似然比8.9,阴性似然比0.2;与以OGTT诊断的DM状态相关的HbA1c临界点为6.2%,敏感性和特异性分别为86.6%和77.5%,曲线下面积0.896(95%CI0.876～0.916),阳性似然比3.9,阴性似然比0.2。与IGT状态相关的FPG临界点为5.1mmol/L,敏感性和特异性分别为65.2%和68.3%,曲线下面积为0.729,阳性似然比2.1,阴性似然比0.5。与IGT状态相关的HbA1c临界点为5.7%,敏感性和特异性分别63.3%和56.5%,曲线下面积为0.634,阳性似然比1.5,阴性似然比0.7。结论6.2mmol/L6.2%时应进一步行OGTT了解2h血糖以明确有无DM,FPG和HbA1c不适用于筛查IGT人群。     

糖化血红蛋白不适用于妊娠糖尿病的筛查和诊断

目的 探讨糖化血红蛋白(HbA1c)在妊娠糖尿病(GDM)筛查与诊断中的价值. 方法 对1815例50g葡萄糖负荷试验(GCT)阳性的孕妇同时测定3hOGTT及HbA1c,比较糖耐量正常(NGT)组、妊娠糖耐量减低(GIGT)组和GDM组HbA1c分布情况,并计算ROC曲线下面积(AUC). 结果 3组HbA1c分布几乎重叠,ROC曲线下面积(AUC)为0.658,95%可信区间为[0.626, 0.690]. 结论 HbA1c不适用于GDM的早期筛查与诊断.     

Glycosylated hemoglobin (Hb AI) as an indicator of therapy effects in different clinical types of diabetes

The levels of glycosylated hemoglobin (Hb AI), intermittent glycemia and glycosuria over 24 hr, Mw index, fasting serum cholesterol and triglycerides, and 24-hr proteinuria were determined in 20 healthy subjects and 88 diabetics representing different clinical types of diabetes mellitus. In each of the subjects all the tests were carried out on a single day. The other investigations included endogenous creatinine clearance, ECG and ophthalmoscopic examination of the eye-fundus. The mean Hb AI levels in the "A" control group (up to 40 yr of age) and in the "B" control group (41-60 yr) were mean +/- SD = 6.8 +/- 0.65% and mean +/- SD = 6.49 +/- 0.99% of the total hemoglobin concentration, respectively. A significant increase in Hb AI concentration was found in all the diabetic patients. The increase, independent of the subject's age, clinical type of diabetes and the therapy employed, was related to the degree of hyperglycemia. In Type I diabetes there was no positive correlation between Hb AI concentration on the one hand and fasting glycemia, the 24-hr profile of glycemia, glycosuria and Mw index on the other. The latter indices of diabetes mellitus control seem thus to differ in value and significance. In Type II diabetes, both newly-diagnosed and of long duration, treated with the sulfonylurea derivatives, a marked correlation was found between Hb AI level and fasting glycemia, the mean value of 8 glycemia determinations over 24-hr, Mw index and 24-hr glycosuria. In Type II diabetes treated with insulin a correlation was established between Hb AI and other findings, except fasting glycemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glycosylated haemoglobin (HbA1c) in iron- and vitamin B12 deficiency

Glycosylated haemoglobin (HbA1c) was measured in 10 patients with iron deficiency anaemia, 10 patients with vitamin B12 deficiency anaemia and 10 healthy controls. Initially there were no significant differences between the groups (P greater than 0.4), but after treatment with iron and vitamin B12 for 3 and 6 weeks, the glycosylated haemoglobin concentration decreased significantly (P less than 0.01). It was concluded that glycosylated haemoglobin is a sensitive marker of the changes in the erythrocyte population that are observed when predominantly immature erythrocytes are being produced.     

Hemoglobin variants detected by hemoglobin A1c (HbA1c) analysis and the effects on HbA1c measurements

Background:

Hemoglobin (Hb) A1c is a tool widely used to monitor long-term glycemic control in diabetic patients. The objective of our study is to compare the HbA1c values measured on high performance liquid chromatography (HPLC) and immunoassay in patients who were detected to have hemoglobin variant after HbA1c analysis.

Materials and Methods:

We compared the HbA1c values measured using the Arkray Adams A1c HA-8160 (HPLC method) and Roche Cobas Integra (immunoturbidimetric method) from diabetic patients who were diagnosed with hemoglobin variants.

Results:

Forty-three diabetic patients were diagnosed with hemoglobin variants: 13 elevated Hb F, 12 Hb E trait, seven Hb S trait, seven Hb D trait, two Hb E / beta-Thalassemia, one Hb C trait, and one homozygous Hb S.

Conclusion:

Knowledge of hemoglobin variants affecting HbA1c measurements is essential, in order to avoid mismanagement of diabetic patients.     

Hemoglobin variants and determination of glycated hemoglobin (HbA1c)

Measurement of glycated hemoglobin in diabetic patients is an established procedure for evaluating long-term control of diabetes. The Diabetes Control and Complications Trial (DCCT), as well as the United Kingdom Prospective Diabetes Study (UKPDS), confirmed the direct relationship between the degree of glycemic control as estimated by glycohemoglobin (GHb) determinations and the development and progression of long-term complications in diabetic patients. Samples with known interferences of HbA(1c) determination as hemoglobinopathies are specifically excluded from certification testing and there are no guidelines or requirements for comparability of samples containing hemoglobin (Hb) variants. This paper reviews the interference of Hb variants on determination methods of glycated hemoglobin as they result in false HbA(1c) results.     

Glycosylated hemoglobin as an index of the prevalence and severity of diabetes in biethnic Fiji

Glycosylated hemoglobin was compared with fasting blood glucose as a screening test for diabetes mellitus and as an index of the severity of diabetes in biethnic (Melanesian and Indian) Fiji. Age-adjusted diabetes prevalence in the test sample was higher in Indians by either criterion. According to the hemoglobin A1 criterion, Melanesians had prevalence rates of 8.2% (males) and 15.8% (females) compared to 17.0% (males) and 24.3% (females) in Indians. In contrast, fasting blood glucose criteria (WHO) gave higher rates in each group. Hemoglobin A1 levels were higher overall in Indians and females. The predictive value of an elevated fasting blood glucose test for an elevated hemoglobin A1 was 20.0% in Melanesians and 60.7% in Indians while that of a normal fasting blood glucose test for a normal hemoglobin A1 was 89.4% in Melanesians and 89.3% in Indians. The proportion of Indians with elevated hemoglobin A1 who were severely hyperglycemic was almost 7 times higher (40.9% vs. 5.8%) than that of Melanesians. The ethnic difference in the predictive value of fasting blood glucose levels for hemoglobin A1 levels appears to be related to the greater severity of hyperglycemia of diabetic Indians compared to diabetic Melanesians. Hemoglobin A1 levels provide information on both the qualitative as well as quantitative differences in diabetes between ethnic groups.     

Fasting plasma glucose as a screening test for gestational diabetes in a multi-ethnic, high-risk population.

AIMS: Screening every pregnant woman for gestational diabetes mellitus (GDM), as widely recommended for high-incidence populations, strains the healthcare system excessively. This study investigated the value of fasting plasma glucose (FPG) as an alternative to the more cumbersome oral glucose tolerance test (OGTT). METHODS: One thousand six hundred and forty-four pregnant women in a multi-ethnic, high-risk population were evaluated by the FPG as a screening test among two principal subgroups, i.e. women (n = 1276) at risk for GDM on clinical grounds and those women (n = 368) with a positive post 50-g, 1-h plasma glucose challenge test (GCT). Two threshold values for FPG 'ruled in or ruled out' a GDM diagnosis, which was confirmed by the 3-h, 100-g OGTT, using Carpenter's modified criteria as the 'gold standard'. RESULTS: In the women with a positive clinical history, at an optimal cut-off value of FPG < 4.4 mmol/l to rule out GDM; a sensitivity of 94.7% was achieved, 21 (1.6%) women being false negatives. Using a FPG > or = 5.3 mmol/l to rule in GDM; the specificity was 94.0% with 53 (4.2%) women being classified as false positives. FPG would have eliminated need for the OGTT in 50.9% pregnant women (misclassification rate 5.8%). In the positive GCT group, using similar cut-offs for FPG, a sensitivity of 96.6% and specificity of 90.8% was achieved with a potential to avoid 51.6% OGTTs (misclassification rate 7.3%). The positive predictive value of the GCT was 31.8% compared to 80.2% for FPG at 5.3 mmol/l. CONCLUSIONS: While previously neglected as a screening test for GDM, in selected high-risk populations the FPG offers a potentially simple, practical algorithm to screen for GDM by being cost-effective and patient friendly. A wider application should be explored.     

Energy consumption for the formation of hemoglobin A1c: a reappraisal and implication on the poor-control diabetes mellitus patients

Diabetes mellitus (DM) is a frequent disorder affecting individuals of all ages. Glycohemoglobin has a key role in the assessment of glycemic control in diabetic patients. Several studies have clearly shown that improved glycemic control is strongly associated with decreased development and/or progression of diabetic complications. The chemical reaction of glycosylation in formation of hemoglobin A_1c (HbA_1c) has been described for decades. Here, the author performed a reappraisal on the bonding energy based on quantum chemical analysis. The author calculated the bonding energy of the reaction and found that the reaction is a type of “energy-consuming reaction.” In addition, the author gives further implication of the findings on the poor-control DM patients. The author hereby proposed that the nature of energy-consuming reaction in formation of hemoglobin A_1c (HbA_1c) is a main underlying for the energy loosing in poorly controlled DM patients. Gathering of the energy from the nearby cellular compartment during formation of HbA_1c might be an important pathological process.     

The rise and fall of HbA1c as a risk marker for diabetes complications

It is still unclear whether short-term, within-day, variability in glycaemic control is contributory to the development of diabetes micro- or macrovascular complications. However, consistent and compelling data are emerging that longer term fluctuations in glucose, as evidenced by increases in HbA_1c variability, do indeed add to the mean HbA_1c value in predicting the risk of microvascular disease. Until now, studies have found this to be the case mainly in type 1 diabetes, but in this issue of Diabetologia (DOI: ) an analysis of the Tsukuba Kawai Diabetes Registry in Japan has found that HbA_1c variability also predicts the risk of nephropathy in type 2 diabetic patients. These observations raise the possibility that reducing rises and falls in HbA_1c may help avoid hyperglycaemia-related vascular disease without running the same risk of hypoglycaemia that a strategy focusing purely on lower HbA_1c might incur.