糖尿病诊断指标糖化血红蛋白的检测方法及临床意义

糖尿病目前已被国际社会列为人类健康头号杀手的非传染性疾病。血糖的检测在糖尿病的诊断、治疗及预防急性和慢性并发症中尤为重要。糖化血红蛋白（glycatedhemoglobin Alc，HbAlc）是反映既往2～3个月平均血糖水平的指标，用于评估长期血糖控制状况。目前HbAlc检测已经被推荐作为糖尿病诊断试验。现对HbAlC的检测方法及其临床意义作一综述。     

Hb Grand Junction (HBB: c.348_349delinsG; p.His117IlefsX42): A New Hyperunstable Hemoglobin Variant

Hyperunstable hemoglobinopathy (HUH) [dominantly inherited β-thalassemia (β-thal)] is a relatively rare form of congenital hemolytic anemia in which mutations occur in the genes encoding for α and β chains, or both chains of the hemoglobin (Hb) molecule. We describe two Hispanic adolescents with a new unstable Hb variant (HBB: c.348_349delinsG; p.His117IlefsX42), resulting from a frameshift mutation at codons 115/116 of the β-globin gene. Both patients also have a 3.7?kb deletion on one α gene, leading to a decreased imbalance between α and β chain formation, and subsequently a milder phenotype than that seen in other hyperunstable Hb variants.     

急性冠脉综合征患者糖化血红蛋白水平与预后的关系

目的 探讨急性冠脉综合征（ACS）患者糖化血红蛋白水平情况及其对ACS患者预后的影响.方法 将102例急性冠脉综合征患者根据糖化血红蛋白水平分为糖化血红蛋白正常组（A组）（HbAlc＜6.5％,n=31例）、糖化血红蛋白低危组（B组）（6.5％＜HbAlc＜7.5％,n=36例）、糖化血红蛋白高危组（C组）（HbAlc＞7.5％,n=35例）3组,分别观察各组入院时、3个月后12个月后的极低密度脂蛋白（VLDL）、C反应蛋白（CRP）、体重指数（BMI）、射血分数（EF）及相关心血管不良事件,如心绞痛、严重心律失常、再发心肌梗死、肺部感染等并发症发生情况.结果 ①A、B组及C组患者入院时VLDL、CRP、BMI及EF值差异无统计学意义（P＞0.05）,而3个月后及12个月后C组EF值较入院时未明显改善（P＞0.05）;②住院及随访12个月期间C组心血管不良事件心绞痛发生率、肺部感染发生率及死亡率较人院时明显增高（P＜0.05）.且HbAlc与心绞痛、严重心律失常、再发心肌梗死、肺部感染及死亡均呈正相关（r=0.412、0.271、0.319、0.251、0.134）.结论 糖化血红蛋白异常可不同程度地升高急性冠脉综合征患者心血管不良事件的发生率.     

Hemoglobins With High Oxygen Affinity Leading to Erythrocytosis. New Variants and New Concepts

This review brings some new insights on erythrocytosis of genetic origin related to problems of oxygen delivery by hemoglobin (Hb). A few molecular mechanisms are individualized among the about 100 Hb variants that cause compensatory erythrocytosis. The most frequently observed structural modifications are localized in the α1β2 interface, or at the C-terminal. They impair formation of a stable T state. Others mutations modify directly or indirectly the surrounding of the heme and the site where oxygen binds. A special interest is brought to the dose effect considering the possibility for formation of hybrid tetramers with altered oxygen binding properties. Homozygous cases, and patients who are compound heterozygotes for a high oxygen affinity Hb and a thalassemia (thal), are discussed. Several examples are provided, specially documented for Hb Olympia [β20(B2)Val→Met] and Hb Saint Nazaire [β103(G5)Phe→Ile]. Other mechanisms leading to erythrocytosis are discussed, and finally, an algorithm is proposed for etiological diagnosis.     

Detection of Hb Anti-Lepore Hong Kong (NG_000007.3: g.63154_70565dup) in Chinese Individuals

We have identified four Chinese individuals from three unrelated families with raised Hb A₂ levels. The anti-Lepore hybrid hemoglobin (Hb) variant was amplified using a pair of primers, 5′ to the β-globin gene Cap site and 3′ to the δ-globin gene polyadenylation site (polyA) region, respectively. Direct sequencing of the βδ fusion products confirmed the anti-Lepore Hong Kong (NG_000007.3: g.63154_70565dup) variant. We found that this anti-Lepore variant is positioned in zone 3 on the capillary electrophoresis system. It may help in differential diagnosis of Hb variants and providing better information in clinical counseling.     

北海地区新生儿脐血血红蛋白电泳实验结果分析

目的了解北海地区新生儿地中海贫血的发病率,为临床诊断及预防提供依据。方法对本院2006年7月～2010年6月共5766份新生儿脐血标本进行琼脂糖电泳,并对Hb区带进行扫描定量分析。结果在5766份脐血标本中,检出Hb Bart阳性（≥1.0%）437例,阳性率为7.579%。根据Hb Bart含量推算,静止型、标准型α-地中海贫血、HbH病、HbBart胎儿水肿综合征的阳性率分别为2.099%、5.376%、0.087%和0.017%。另外发现异常血红蛋白病共17例,发生率为0.295%,其中HbE11例,HbG2例,HbC-S1例,HbJ 2例,HbK1例。结论北海市属于地中海贫血高发区,使用全自动电泳仪对脐血定量检测分析能早期、方便地对新生儿α-地中海贫血进行筛查。     

A Clinical Update of the Hb Siirt [β27(B9)Ala→Gly; HBB: c.83C>G] Hemoglobin Variant

We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly; HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (–CT) (HBB: c.17_18delCT) frameshift mutation and of the ααα ^{anti 3.7} triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ～40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and ααα^{anti 3.7} triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82?G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β⁺-thalassemia (β⁺-thal) phenotype.