Here is a quiet quality-of-care issue that hides in plain sight: the hemoglobin A1C assay can be unreliable in patients with sickle cell trait (SCT). Depending on the method your lab runs, A1C can read falsely high or falsely low — meaning your "well-controlled" patient may actually be hyperglycemic, or your "uncontrolled" patient may be receiving treatment they don't need.
This isn't a small population. SCT affects roughly 1 in 12 Black or African American patients in the U.S., plus meaningful numbers of patients with Mediterranean, Middle Eastern, South American, and South Asian heritage. If you treat diabetes, you treat SCT.
Three things every primary care, endocrinology, and internal medicine clinician should do:
1. Know your patient's hemoglobin status. SCT is identified through hemoglobin electrophoresis, HPLC, or DNA testing — not through the A1C itself. An A1C that flags a "variant hemoglobin" is a signal, not a diagnosis. Confirm separately.
2. Know your lab's method. Call your reference lab and ask which A1C method they use, and whether it is validated for HbS interference. The National Glycohemoglobin Standardization Program (NGSP) maintains a public list of which methods are reliable in the presence of common hemoglobin variants. Bookmark it: ngsp.org/interf.asp.
3. Have a backup plan. If your lab's method is affected by HbS, supplement A1C with fructosamine, glycated albumin, or continuous glucose monitoring to confirm glycemic control. Don't titrate insulin off a number you can't trust.
A note on equity. Patients with SCT have historically received the same A1C-driven care as everyone else, even when the test was misleading them. That's a measurable contributor to disparate diabetes outcomes in Black communities. Fixing it costs nothing — a phone call to the lab and a habit of asking, "Has this patient ever been tested for hemoglobin variants?"
When the A1C and the clinical picture don't match, trust your eyes and order the better test.
— Dr. Rob
📄 Resource: CDC Sickle Cell Trait and Diabetes Tests: What Every Healthcare Provider Should Know.