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Screening BODY HANDBOOK
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HbA1c Limitations
The A1c test is the standard three-month blood-sugar summary, and for most people it's fair. For roughly one patient in four or five, it silently isn't. Iron deficiency, a sickle or thalassemia trait, kidney disease, a recent transfusion, or late pregnancy can shift your number enough to flip a diabetes diagnosis or push you into avoidable low-sugar episodes. Two questions decide it: are you one of those people, and if so, what should you measure instead?
Know Evidence Moderate Chapter Screening

The test doesn't measure your blood sugar. It measures the fraction of your hemoglobin with glucose stuck to it, built up over a red cell's roughly 120-day lifetime 1. If your red cells die early, from blood loss, late pregnancy, or dialysis, the A1c reads low while your sugar is high. If they live longer, as in iron deficiency, it reads high while your sugar is fine 2. Sickle, HbC, HbE, and thalassemia traits, silent in carriers and common across Africa, the Mediterranean, and South and Southeast Asia, fool the assay itself, so the same blood reads differently on different machines 3.

The error is big enough to matter. At the same true glucose, lab A1c spreads about one and a half percentage points between people, so two patients with identical sugar can land on opposite sides of the 6.5% diabetes line 4. Sickle-trait carriers read about a third of a point low, so their diabetes gets missed more often 5. Iron deficiency biases it up by a third to a full point until iron is replaced 6. In dialysis at a lab 7%, real glucose runs about 30 mg/dL hotter 7.

The whole entry is five asks at the lab counter.

What to ask for instead. Fasting glucose and the two-hour glucose tolerance test measure sugar directly, cheap and on every panel; fasting above 126 mg/dL or two-hour above 200 mg/dL diagnoses diabetes whatever the A1c says 8. Fructosamine tracks glucose on blood proteins over two to three weeks and skips every red-cell problem, useful for monitoring 9. An over-the-counter glucose patch reads sugar every minute for two weeks, reports time-in-range directly, and runs about $50โ€“100 10. If the patch and your lab A1c disagree by over half a point, trust the patch 11.

The fine print โ€” when to skip it, and what people get wrong

Use a glucose test, not A1c, to decide with active hemolysis or sickle cell disease, thalassemia major, dialysis, a late-pregnancy trimester, a recent transfusion, or a hemoglobin variant your lab can't handle 8, 3.

Two clinic myths. "A1c is your average sugar": it's a proxy, with biology in between. And two people at the same A1c aren't equal: one steady at 150, one swinging 60 to 280 12.

Who this hurts. The kidney patient overtreated into night-time lows 7; the carrier diagnosed years late 5; the iron-deficient woman labelled prediabetic until iron clears it 6.

References
  1. 1Cohen RM, Franco RS, Khera PK, Smith EP, Lindsell CJ, Ciraolo PJ, Palascak MB, Joiner CH (2008). Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood. link
  2. 2Khera PK, Smith EP, Lindsell CJ, Rogge MC, Haggerty S, Wagner DA, Palascak MB, Mehta S, Hibbert JM, Joiner CH, Franco RS, Cohen RM (2015). Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation. American Journal of Hematology. link
  3. 3NGSP (2023). HbA1c Assay Interferences. link
  4. 4Beck RW, Connor CG, Mullen DM, Wesley DM, Bergenstal RM (2017). The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading. Diabetes Care. link
  5. 5Lacy ME, Wellenius GA, Sumner AE, Correa A, Carnethon MR, Liem RI, Wood AC, Winkler CA, Carson AP, Sims M, Bertoni AG, Kanaya AM, Wassel CL (2017). Association of Sickle Cell Trait With Hemoglobin A1c in African Americans. JAMA. link
  6. 6Coban E, Ozdogan M, Timuragaoglu A (2004). Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. Acta Haematologica. link
  7. 7Lo C, Lui M, Ranasinha S, Teede HJ, Kerr PG, Polkinghorne KR, Nathan DM, Zoungas S (2014). Defining the relationship between average glucose and HbA1c in patients with type 2 diabetes and chronic kidney disease. Diabetes Research and Clinical Practice. link
  8. 8American Diabetes Association (2024). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. link
  9. 9Wright LA, Hirsch IB (2014). The Challenge of the Use of Glycemic Biomarkers in Diabetes: Reflecting on Hemoglobin A1C, 1,5-Anhydroglucitol, and the Glycated Proteins Fructosamine and Glycated Albumin. Diabetes Spectrum. link
  10. 10Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, et al. (2019). Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. link
  11. 11Bergenstal RM, Beck RW, Close KL, Grunberger G, Sacks DB, Kowalski A, et al. (2018). Glucose Management Indicator (GMI): A New Term for Estimating A1C From Continuous Glucose Monitoring. Diabetes Care. link
  12. 12Hirsch IB (2015). Glycemic Variability and Diabetes Complications: Does It Matter? Of Course It Does! Diabetes Care. link
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