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LETTER

Fetal Hemoglobin and the Glycosylated Hemoglobin Assay

right arrow David M. Grossman, MD; Gregory A. Doyle, MD; and Robert D. Hoeldtke, MD, PhD

15 March 1994 | Volume 120 Issue 6 | Page 524


TO THE EDITOR:

We describe a 71-year-old woman with type II diabetes who had discordant indices of glycemic control. Over a 3-month period, her preprandial plasma glucose concentrations varied between 48 and 127 mg/dL, with a mean of 89 mg/dL. Her glycosylated hemoglobin values, however, were 13.9%, 15.0%, and 16.9%, respectively. Her plasma fructosamine was 267 µmol/L (normal range, 174 to 2861 µmol/L).

Because of this discrepancy, we did a standard hemoglobin electrophoresis that showed a markedly elevated fetal hemoglobin level (9.5%). The patient was not anemic and had a normal mean corpuscular volume without microcytosis.

Persistent elevation of fetal hemoglobin levels can interfere with glycosylated hemoglobin measurement depending on the assay used. This factor may be a greater problem in patients with type I diabetes, in which onset occurs before 6 years of age [1, 2]. A study of 5300 diabetic patients by Allen and colleagues [3] showed 0.25% to have elevated fetal hemoglobin levels. Lahtela and associates [4] studied 930 consecutive adult clinic patients, and found elevated fetal hemoglobin levels in 6.5% of diabetic patients and in 1.6% of matched controls. In some electrophoresis systems, fetal hemoglobin migrates to the same position as hemoglobin A1, and their peaks superimpose. Analysis with high-performance liquid chromatography provides better resolution between fetal hemoglobin and hemoglobin A1.

The utility of glycosylated hemoglobin assays in diabetic patients with known hemoglobin variants needs to be assessed. In the patient with an elevated fetal hemoglobin F level, options include analysis of specimens with both the hemoglobin A1 assay and standard electrophoresis, hemoglobin A1 by high-performance liquid chromatography, or the measurement of other glycosylated proteins with shorter half-lives such as plasma fructosamine [4].


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West Virginia University School of Medicine; Morgantown, WV 26506


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1. Mullis P, Schuler J, Zuppinger K. Increased prevalence of fetal hemoglobin in type I (insulin-dependent) diabetes mellitus. Diabetologia. 1989; 32:227-30.

2. Thivolet C, Goujon R, Vassy V, Revol A, Tourniaire J. Interference of elevated fetal hemoglobin on HbA1c measurements in adult type I diabetic patients (Letter). Diabetes Care. 1991; 14:1108.

3. Allen KR, Hamilton AD, Bodansky HJ, Poon P. Prevalence of haemoglobin variants in a diabetic population and their effect on glycated haemoglobin measurement. Ann Clin Biochem. 1992; 29:426-9.

4. Lahtela JT, Koskinen L, Koivula T. Elevated fetal hemoglobin among diabetic patients. Abstract 64. American Diabetes Association 53rd Annual Meeting; 13 June 1993.

5. Johnson RN, Metcalf PA, Baker JR. Fructosamine: a new approach to the estimation of serum glycosylprotein. An index of diabetic control. Clin Chimica Acta. 1982; 127:87-95.

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