A 63-year-old White woman presents to an endocrine clinic for evaluation of a glycated hemoglobin A1c (HbA1c) level of 10% in April 2019. The patient has no prior medical history of diabetes, prediabetes, or gestational diabetes and is asymptomatic. She is not on any antihyperglycemic agents. The patient is otherwise healthy with no other pertinent medical issues and no past surgical history. There is no family history of diabetes. She is not taking any medications or supplements other than an over-the-counter multivitamin. She denies using alcohol, illicit drugs, or tobacco products. The patient is asymptomatic and the physical examination is normal.
A review of laboratory reports shows a normal HbA1c level of 5.5% at a visit 6 months prior. There are no other HbA1c tests in her medical record and fasting serum glucose levels were always <100 mg/dL.
In June 2019, blood work is ordered and her HbA1c is 9.8%. The measure is repeated 1 month later in July 2019 and remains elevated at 9.8%. A comprehensive laboratory evaluation follows to assess for an underlying cause of her elevated HbA1c. This workup includes the following measurements, all of which are within normal limits: iron, salicylates, lipids, vitamin B12, folate panel, lead, vitamin E, thyroid function, complete blood count with differential, and comprehensive metabolic panel.
A fructosamine level is obtained and shows a result of 220 µmol, which is in the normal range. This measure provides an estimate of long-term glycemic control. Her fructosamine level is equivalent to an HbA1c value of <6%, which is inconsistent with the patient’s HbA1c laboratory value of 10% in November 2019. Hemoglobin electrophoresis/hemoglobin fractionated reveals a possible case of alpha thalassemia.
The patient returns to the clinic with the results of her home blood glucose testing but was only checking the fasting level, which is well within the normal range (<100 mg/dL). As there are no random or postprandial glucose readings and to further evaluate her glycemic patterns the patient agrees to wear a 14-day continuous glucose monitor. The results show that the daily average blood glucose over the 11 days of wear was 99 mg/dL, which indicates an HbA1c of 5.1%.
The patient returns for follow-up 11 months later in October 2020. The continuous glucose monitor test is repeated and shows a similar result with a normal 14-day average blood glucose level (82 mg/dL, indicating an HbA1c of 4.5%); however, her HbA1c remains elevated at 10.2% (Table).
Table 1: Review of HbA1c With Corresponding Fasting Serum Glucose Level
|Date||HbA1c (%)||Fasting Serum Glucose (mg/dL)|
Diabetes mellitus remains one of the major causes of illness and death worldwide. The prevalence of diabetes is rising at an alarming rate in the United States. According to the Centers for Disease Control and Prevention National Diabetes Statistics Report for 2020, the prevalence of diabetes in the United States has risen to an estimated 34.2 million people (or 10.5% of the US population).1 In 2018, an estimated 26.8 million adults aged 18 years and older (or 10.2% of the US population) had diagnosed diabetes and approximately 7.3 million people had undiagnosed diabetes.1
In 2017, diabetes was the seventh leading cause of death in the United States.1 Diabetes can affect many parts of the body and is associated with serious complications including heart disease, stroke, blindness, kidney failure, lower-limb amputation, and death.1
The most widely used clinical test to estimate mean blood glucose level is HbA1c measurement. Since its first introduction into clinical use in the 1970s, HbA1c has remained the standard biomarker of long-term glycemic control and its role broadened in 2010 when the American Diabetes Association (ADA) added it as a diagnostic criterion.2,3 In the 2020 ADA guidelines, the diagnostic criteria for diabetes in asymptomatic adults include the following4:
- Fasting plasma glucose values ≥126 mg/dL (7.0 mmol/L);
- 2-hour plasma glucose values ≥200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT); or
- A1C value ≥6.5% (48 mmol/mol)
The HbA1c measurement reflects the mean blood glucose over the entire 120-day lifespan of the red blood cell.3,5,6 Because of the integral role of HbA1c in diagnosis and treatment, it is important for clinicians in practice to quickly recognize clinical scenarios and interfering factors that may yield false results. Falsely elevated HbA1c can be detrimental and potentially fatal if insulin is administered in a patient with euglycemia.