PDF(Pubmed)
Abstract：
BACKGROUND: Glycated hemoglobin is a well-known marker for evaluating long-term glycemic control. However, the accuracy of glycated hemoglobin measurement can be affected by the presence of hemoglobin variants, which makes the determination and interpretation of glycated hemoglobin values in terms of glycemic control not only difficult but also misleading. Here we present the first ever case of a patient with type 2 diabetes with hemoglobin E from Nepal, diagnosed incidentally because of spurious glycated hemoglobin levels.
METHODS: A 45-year-old Hindu Mongolian female with a history of type 2 diabetes for around 9 years but not very compliant with follow-ups was referred to our facility for plasma fasting and postprandial blood glucose levels and glycated hemoglobin. Fasting and postprandial blood sugars were found to be high. A consistent very low glycated hemoglobin by two different high-performance liquid chromatography (HPLC) methods compelled us to call the patient for a detailed clinical history and for the records of investigations done in the past. The patient has been a known case of type 2 diabetes for around 9 years and presented irregularly for follow-up visits. Around 4 years ago, she presented to a healthcare facility with fatigue, severe headaches, pain in the abdomen, discomfort, and dizziness for a couple of months, where she was shown to have high blood glucose. She was referred to a tertiary-level hospital in Kathmandu, where she was prescribed metformin 500 mg once daily (OD). Due to her abnormal hemoglobin A1c reports, she was then sent to the National Public Health Laboratory for repeat investigations. Her blood and urine investigations were sent. Complete blood count findings revealed high red blood cell and white blood cell counts, a low mean corpuscular volume, and a high red cell distribution width-coefficient of variation. Other parameters, including serum electrolytes, renal function tests, liver function tests, and urine routine examinations, were within normal limits. A peripheral blood smear revealed microcytic hypochromic red cells with some target cells. Hemoglobin electrophoresis showed a very high percentage of hemoglobin E, a very low percentage of hemoglobin A2, and normal proportions of hemoglobin A and hemoglobin F. A diagnosis of homozygous hemoglobin E was made, and family screening was advised.
CONCLUSIONS: Clinicians should be aware of the limitations of glycated hemoglobin estimation by ion exchange high-performance liquid chromatography in patients with hemoglobin E and other hemoglobin variants. If the clinical impression and glycated hemoglobin test results do not match, glycated hemoglobin values should be determined with a second method based on a different principle, and glycemic status should be confirmed through alternative investigations, preferably those that are not influenced by the presence of hemoglobin variants (for example, boronate affinity chromatography, fructosamine test, glycated albumin test, the oral glucose tolerance test, continuous glucose monitoring, etc.). Consistent or even doubtful results should also raise the suspicion of a hemoglobin variant, which should be confirmed through further evaluation and investigations.
METHODS: A 45-year-old Hindu Mongolian female with a history of type 2 diabetes for around 9 years but not very compliant with follow-ups was referred to our facility for plasma fasting and postprandial blood glucose levels and glycated hemoglobin. Fasting and postprandial blood sugars were found to be high. A consistent very low glycated hemoglobin by two different high-performance liquid chromatography (HPLC) methods compelled us to call the patient for a detailed clinical history and for the records of investigations done in the past. The patient has been a known case of type 2 diabetes for around 9 years and presented irregularly for follow-up visits. Around 4 years ago, she presented to a healthcare facility with fatigue, severe headaches, pain in the abdomen, discomfort, and dizziness for a couple of months, where she was shown to have high blood glucose. She was referred to a tertiary-level hospital in Kathmandu, where she was prescribed metformin 500 mg once daily (OD). Due to her abnormal hemoglobin A1c reports, she was then sent to the National Public Health Laboratory for repeat investigations. Her blood and urine investigations were sent. Complete blood count findings revealed high red blood cell and white blood cell counts, a low mean corpuscular volume, and a high red cell distribution width-coefficient of variation. Other parameters, including serum electrolytes, renal function tests, liver function tests, and urine routine examinations, were within normal limits. A peripheral blood smear revealed microcytic hypochromic red cells with some target cells. Hemoglobin electrophoresis showed a very high percentage of hemoglobin E, a very low percentage of hemoglobin A2, and normal proportions of hemoglobin A and hemoglobin F. A diagnosis of homozygous hemoglobin E was made, and family screening was advised.
CONCLUSIONS: Clinicians should be aware of the limitations of glycated hemoglobin estimation by ion exchange high-performance liquid chromatography in patients with hemoglobin E and other hemoglobin variants. If the clinical impression and glycated hemoglobin test results do not match, glycated hemoglobin values should be determined with a second method based on a different principle, and glycemic status should be confirmed through alternative investigations, preferably those that are not influenced by the presence of hemoglobin variants (for example, boronate affinity chromatography, fructosamine test, glycated albumin test, the oral glucose tolerance test, continuous glucose monitoring, etc.). Consistent or even doubtful results should also raise the suspicion of a hemoglobin variant, which should be confirmed through further evaluation and investigations.
摘要：
背景：糖化血红蛋白是用于评估长期血糖控制的众所周知的标志物。然而,糖化血红蛋白测量的准确性可能会受到血红蛋白变体的影响，这使得糖化血红蛋白值在血糖控制方面的测定和解释不仅困难而且具有误导性。在这里，我们介绍了首例来自尼泊尔的2型糖尿病患者的血红蛋白E，偶然诊断是因为虚假的糖化血红蛋白水平。
方法：一名45岁的印度裔蒙古族女性，有约9年的2型糖尿病病史，但随访时间不是很好，她被转诊到我们的机构，以检测空腹血浆和餐后血糖水平以及糖化血红蛋白。发现空腹和餐后血糖很高。通过两种不同的高效液相色谱（HPLC）方法获得的一致的极低糖化血红蛋白迫使我们致电患者以获取详细的临床病史和过去进行的调查记录。该患者是已知的2型糖尿病病例约9年，并不定期进行随访。大约4年前,她带着疲劳去了一家医疗机构，严重的头痛,腹部疼痛，不适,头晕了几个月，在那里她被证明有高血糖。她被转诊到加德满都的一家三级医院,其中她被处方二甲双胍500毫克，每日一次（OD）。由于她的血红蛋白A1c异常报告，然后，她被送往国家公共卫生实验室进行重复调查。她的血液和尿液检查已发送。全血细胞计数结果显示红细胞和白细胞计数高，较低的平均红细胞体积，和较高的红细胞分布宽度变异系数。其他参数,包括血清电解质,肾功能试验,肝功能检查,和尿常规检查，在正常范围内。外周血涂片显示微细胞低色素红细胞和一些靶细胞。血红蛋白电泳显示血红蛋白E的百分比非常高，血红蛋白A2的百分比非常低，血红蛋白A和血红蛋白F的比例正常。建议进行家庭筛查。
结论：临床医生应该意识到通过离子交换高效液相色谱法评估血红蛋白E和其他血红蛋白变体患者糖化血红蛋白的局限性。如果临床印象与糖化血红蛋白检测结果不符，糖化血红蛋白值应该用基于不同原理的第二种方法来确定，和血糖状态应该通过替代调查来确认，优选不受血红蛋白变体存在影响的那些（例如，硼酸酯亲和层析,果糖胺试验,糖化白蛋白试验,口服葡萄糖耐量试验，连续血糖监测,等。).一致甚至可疑的结果也应该引起对血红蛋白变异的怀疑，这应该通过进一步的评估和调查来确认。
方法：一名45岁的印度裔蒙古族女性，有约9年的2型糖尿病病史，但随访时间不是很好，她被转诊到我们的机构，以检测空腹血浆和餐后血糖水平以及糖化血红蛋白。发现空腹和餐后血糖很高。通过两种不同的高效液相色谱（HPLC）方法获得的一致的极低糖化血红蛋白迫使我们致电患者以获取详细的临床病史和过去进行的调查记录。该患者是已知的2型糖尿病病例约9年，并不定期进行随访。大约4年前,她带着疲劳去了一家医疗机构，严重的头痛,腹部疼痛，不适,头晕了几个月，在那里她被证明有高血糖。她被转诊到加德满都的一家三级医院,其中她被处方二甲双胍500毫克，每日一次（OD）。由于她的血红蛋白A1c异常报告，然后，她被送往国家公共卫生实验室进行重复调查。她的血液和尿液检查已发送。全血细胞计数结果显示红细胞和白细胞计数高，较低的平均红细胞体积，和较高的红细胞分布宽度变异系数。其他参数,包括血清电解质,肾功能试验,肝功能检查,和尿常规检查，在正常范围内。外周血涂片显示微细胞低色素红细胞和一些靶细胞。血红蛋白电泳显示血红蛋白E的百分比非常高，血红蛋白A2的百分比非常低，血红蛋白A和血红蛋白F的比例正常。建议进行家庭筛查。
结论：临床医生应该意识到通过离子交换高效液相色谱法评估血红蛋白E和其他血红蛋白变体患者糖化血红蛋白的局限性。如果临床印象与糖化血红蛋白检测结果不符，糖化血红蛋白值应该用基于不同原理的第二种方法来确定，和血糖状态应该通过替代调查来确认，优选不受血红蛋白变体存在影响的那些（例如，硼酸酯亲和层析,果糖胺试验,糖化白蛋白试验,口服葡萄糖耐量试验，连续血糖监测,等。).一致甚至可疑的结果也应该引起对血红蛋白变异的怀疑，这应该通过进一步的评估和调查来确认。
