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A 45-year-old woman with a 20-year history of type 1 diabetes mellitus that has been complicated by nephropathy and retinopathy is referred for help achieving better glycemic control. Her current regimen consists of insulin glargine once daily and insulin lispro with meals, but she is interested in insulin pump therapy. Self-monitoring of blood glucose (8 times daily) shows values ranging between 150 and 300 mg/dL (8.3-16.7 mmol/L). Her hemoglobin A1c level has been between 8.5% and 10% (69-86 mmol/mol). Her menses are regular. She has sickle cell disease, without recent crises. Her medications include aspirin, ramipril, and atorvastatin.
Laboratory test results:
- Hemoglobin A1c = 9% (75 mmol/mol)
- Serum creatinine = 2.2 mg/dL (194.5 mmol/L)
- Urine albumin-to-creatinine ratio = 3886 mg/g
- Liver function tests, normal
- TSH = 7.5 mIU/L
- Serum fructosamine = 210 mmol/L (reference range, 205-285 mmol/L)
The discrepancy between this patient’s hemoglobin A1c and fructosamine levels is most likely caused by which of the following?
- Laboratory error
- Sickle cell disease
The turnover of serum proteins, mainly albumin, is more rapid than that of hemoglobin; thus, serum fructosamine (glycated proteins, mostly albumin) values reflect mean blood glucose values over a much shorter period (1 to 2 weeks). There is generally a good correlation between serum fructosamine and hemoglobin A1c values. Fructosamine responds more rapidly with changes in blood glucose control than does hemoglobin A1c. Falsely low fructosamine values in relation to mean blood glucose values occur with rapid albumin turnover, for example, in patients with protein-losing enteropathy or nephrotic syndrome (Answer E). Sickle cell disease (Answer B), hemolysis (Answer C), and hypothyroidism (Answer D) do not falsely lower fructosamine. Laboratory errors (Answer A) do rarely occur, but in this case, the heavy proteinuria explains the normal fructosamine value.
Identify nephrotic syndrome as a cause of falsely low fructosamine.
Vetter SW. Glycated serum albumin and AGE receptors. Adv Clin Chem. 2015;72:205-275.
Koga M. Glycated albumin; clinical usefulness. Clin Chim Acta. 2014;433:96-104.
Parrinello CM, Selvin E. Beyond HbA1c and glucose: the role of nontraditional glycemic markers in diabetes diagnosis, prognosis, and management. Curr Diab Rep. 2014;14(11):548.