The A1c That Doesn't Match the Meter: Dialysis, Anemia, and a 'Great' Number
A 63-year-old man with type 2 diabetes and end-stage kidney disease is on in-home hemodialysis three times weekly. His chart lists an A1c of 6.3%, metformin 1000 mg twice daily, insulin glargine 22 units, and insulin aspart 6 units with meals. Over two weeks his logbook shows pre-dialysis glucose of 180–220 mg/dL, glucose of 62–70 mg/dL during the last hour of dialysis twice, and one nocturnal low of 58 mg/dL. Hemoglobin is 9.8 g/dL; he has iron deficiency and received IV iron and an erythropoiesis-stimulating agent 3 weeks ago, plus a 2-unit transfusion after a recent catheter-related admission. He reports burning in both feet. He asks, 'My A1c is great, so why do I feel so bad?'
1. Why is the A1c not interpretable in this patient, and in which direction is it biased? What should replace it?
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His A1c is a measurement artifact, and it is biased downward - his true average glucose is considerably higher than 6.3%.
Contributors, in this case all pushing the same direction:
- Uremia shortens red cell survival, so glycated hemoglobin has less time to accumulate - falsely low.
- Erythropoiesis-stimulating agent and IV iron produce a wave of young reticulocytes with little glycation - falsely low.
- Recent transfusion introduces donor red cells with normal-to-low glycation - falsely low.
- Carbamylated hemoglobin in renal failure can interfere with some assay methods.
- (Iron deficiency alone, before treatment, biases the other way - falsely high - which is part of why the sequence of treatments makes this number impossible to interpret.)
Corroborating evidence that the number is wrong: logbook values of 180–220 mg/dL pre-dialysis and multiple lows in the 58–70 range are not consistent with an A1c of 6.3%.
Replace it with:
- CGM - the right tool for someone on insulin with hypoglycemia; it captures the dialysis-day troughs, overnight risk, and time in range. Interpret GMI with the same caveat about red cell lifespan; treat it as an estimate, not a lab result.
- Structured self-monitoring if CGM is unavailable: pre- and post-dialysis, bedtime, and a 2–3 a.m. check.
- Trends and time in range rather than a single averaged number.
Say it plainly to him: 'That number is measuring your blood, not your sugar. It's wrong, and it's wrong in the direction that makes you look better than you are.'
2. What medication changes are needed, and how do you handle insulin around dialysis?
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Stop metformin today; then rebuild the insulin schedule around dialysis and meals.
- Metformin - stop. At eGFR <30 and on dialysis, it is contraindicated: accumulation and lactic acidosis risk, with no offsetting benefit. It has clearly been carried forward from before his kidneys failed.
- The dialysis-day lows are mechanistically predictable: dialysis removes uremic toxins and improves insulin sensitivity, glucose can be lost into dialysate, and insulin clearance changes. A glucose of 62–70 in the last hour of dialysis twice is a pattern, not noise.
- Reduce the insulin that is active during dialysis. Lower the pre-dialysis aspart dose (or omit it if he is not eating a full meal), consider reducing the basal dose the morning of dialysis, and discuss with the dialysis team whether dialysate glucose can be adjusted. On non-dialysis days the requirement may be higher.
- Address the nocturnal 58 mg/dL by reducing bedtime basal and reviewing the evening meal bolus; a CGM with alarms is the practical safeguard.
- If additional glucose lowering is needed, a DPP-4 inhibitor such as linagliptin needs no renal adjustment and carries minimal hypoglycemia risk. Sulfonylureas - especially glyburide - should be avoided. SGLT2 inhibitors have little glucose-lowering effect at this level of kidney function.
- Deprescribe anything not actively earning its place. His list should be reviewed line by line each admission or dialysis change.
3. Set the monitoring targets, and address the burning feet and what to tell him about his 'good' number.
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Targets should be individualized and anchored in avoiding lows, not in reaching a population A1c goal.
- Glucose range focus: aim for substantial time in 70–180 mg/dL while keeping time below 70 mg/dL minimal - under 1–4% - and essentially no values below 54. Many patients on dialysis are reasonably managed with an A1c-equivalent in the 7.0–8.0% range; the guiding constraint is hypoglycemia, which is far more immediately dangerous than mild hyperglycemia in this population.
- Monitoring schedule: CGM if feasible, with review at each dialysis encounter; otherwise pre- and post-dialysis, pre-meal, bedtime, and a periodic overnight check.
- The burning feet warrant a proper foot exam: monofilament, vibration sense, pulses, skin integrity, and footwear inspection. Distal symmetric polyneuropathy in a patient on dialysis is common and multifactorial, but it drives the two things that matter most here - foot ulcer and amputation risk. Refer to podiatry, teach daily foot checks with a mirror, and emphasize never walking barefoot. Screen for other contributors: B12 deficiency, thyroid disease, and, importantly, whether the pain is neuropathic versus ischemic.
- Also reassess blood pressure and volume status - cardiovascular death dominates the risk profile at this stage, and glucose is a secondary lever compared with volume, potassium, and access care.
- What to tell him: his A1c was falsely low because of his kidney disease, the anemia treatment, and the transfusion; his actual glucose has been running high with dangerous dips; the plan is to remove a medication that is now unsafe and to adjust insulin so dialysis does not drop him into the 60s. Frame the goal as 'fewer lows and steadier days,' which is what he will actually feel.