3rd Place Poster Winner

As a geriatrician dedicated to improving the accuracy and quality of care for older adults, I am pleased to share insights from our recent case study on a geriatric patient with an abnormally low Hemoglobin A1c (HbA1c) level caused by an undiagnosed hemoglobinopathy. This case, managed at the Division of Geriatric Medicine at Eisenhower Health, highlights critical pitfalls in diabetes diagnostics and emphasizes the need for heightened clinician awareness.

Our study underscores the importance of recognizing atypical clinical scenarios that affect the accuracy of HbA1c measurements, which are a cornerstone in diagnosing and managing diabetes. I want to take this opportunity to share the lessons from this case and raise awareness about alternative approaches for effective diabetes management.

What is HbA1c, and Why Does It Matter?

Hemoglobin A1c (HbA1c) is a widely used diagnostic tool for diabetes, reflecting average blood glucose levels over three months. First recommended by the American Diabetes Association in 2010 as a diagnostic criterion, it has become indispensable for managing and predicting diabetes-related outcomes. Despite its benefits, several clinical scenarios, such as hemoglobinopathies, may significantly impair the accuracy of this test.

The Case: Abnormally Low HbA1c in a Geriatric Patient

Our patient, a 75-year-old female with a history of hyperlipidemia, osteopenia, and osteoarthritis, presented to establish care in our geriatric clinic. While her initial physical exam and laboratory results were within normal limits, her HbA1c level was abnormally low (<3.5%), despite normal fasting glucose (85 mg/dL) and no clinical symptoms of hypoglycemia.

Further evaluations, including a hemoglobinopathy panel, identified an alpha hemoglobin variant (Hb I-Texas). Gene sequencing confirmed heterozygosity for the Hb I-Texas mutation (c.49A>G in the alpha 2-globin gene). This hemoglobinopathy explained her falsely low HbA1c level, highlighting a diagnostic challenge where routine diabetes tests might yield misleading results.

Exhibit 1-1: Clinical Scenarios Causing False HbA1c Results

Why This Matters

This case demonstrates the limitations of relying solely on HbA1c levels for diagnosing and monitoring glucose disorders, especially in patients with hemoglobinopathies. Without further testing, such atypical results could lead to misdiagnosis or missed diagnosis of diabetes.

Lessons Learned

• Recognizing Diagnostic Pitfalls:
  Clinicians should remain vigilant for conditions such as hemoglobinopathies that may skew HbA1c results. Exhibit 1-1 outlines additional clinical scenarios that could falsely increase or decrease HbA1c levels, such as anemia, chronic illnesses, and certain medications.

• Alternative Diagnostic Tools:
  In cases where HbA1c cannot be reliably utilized, alternative measures recommended by the American Diabetes Association include:

• Fasting plasma glucose (≥126 mg/dL)

• Random plasma glucose (≥200 mg/dL with hyperglycemia symptoms)

• Oral glucose tolerance testing (≥200 mg/dL at 2 hours)

• Monitoring with fructosamine or glucose logs for long-term management.

What Should Be Done?

This case emphasizes the need for clinicians to adapt their diagnostic strategies in atypical scenarios. Based on this study, I recommend the following:

1. Enhanced Awareness and Education:

• Increase clinician awareness of hemoglobinopathies and other syndromes that impact HbA1c accuracy.

• Include hemoglobinopathy screening in diagnostic workflows for unexplained HbA1c anomalies.

2. Utilization of Alternative Tests:

• Leverage fasting glucose, oral glucose tolerance testing, and fructosamine as adjunctive or replacement markers in complex cases.

3. Multidisciplinary Approach:

• Collaborate with specialists, including hematologists and endocrinologists, for accurate diagnosis and management.

My Message to Clinicians and Healthcare Teams

This case underscores the need for tailored diagnostic approaches in geriatric care, especially when managing conditions as prevalent as diabetes. By remaining vigilant for atypical findings and employing alternative diagnostic tools, clinicians can ensure accurate diagnoses and effective patient management.

I invite healthcare teams to engage in discussions about improving diagnostic strategies and leveraging multidisciplinary approaches to tackle such challenges. Together, we can enhance the quality of diabetes care for our patients.

Kourosh A.P. Moshiri, MD, EMHA, FACP, AGSF, CMD, HMDC, FACCWS

Internal Medicine Section Chief, Eisenhower Medical Center
Associate Medical Director, Eisenhower Geriatric Medicine Fellowship Program
Medical Director, Desert Mountain Care Center
Associate Clinical Professor, UCR, School of Medicine

References

• Bry, L., Chen, P.C., & Sacks, D.B. (2001). Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clinical Chemistry, 47(2), 153-163.

• Schneier, R.G., Hightower, B., Hosty, T.S., Ryder, H., Tomlin, G., & Jones, R.T. (1976). Abnormal hemoglobins in a quarter million people. Blood Hemoglobinopathies, 48(6), 629–637.

• Tran, H., Silva, D., & Petrovsky, N. (2004). Potential pitfalls of using hemoglobin A1c as the sole measure of glycemic control. Clinical Diabetes, 22(3), 141-143.

• Gillery, P., Hue, G., Bordas-Fonfrede, M., Chapelle, J.P., et al. (2000). Hemoglobin A1c determination and hemoglobinopathies: Problems and strategies. Annals of Biology and Clinical Pathology (Paris), 58(6), 425–429.

• Weykamp, C.W., Penders, T.J., Muskiet, F.A.J., & van der Slik, W. (1993). Influence of hemoglobin variants and derivatives on glycohemoglobin determinations, as investigated by 102 laboratories using 16 methods. Clinical Chemistry, 39(8), 1717–1723.

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