Today, I review, link to, and excerpt from CoreIM‘s Hemoglobin A1c and Glucose Measurements.
All that follows is from the above resource.
Posted: April 26, 2023
By: Dr. Cary Blum, Dr. Shreya P. Trivedi, Dr. Yichi Zhang and Dr. Greg Katz
Graphic: Manasi Danayak
Audio: Yichi ZhangPodcast: Play in new window | Download
Time Stamps
- 00:00 Introduction
- 00:35 Random Glucose, Fasting Glucose, Glucose Tolerance Test
- 03:03 Hemoglobin A1c
- 08:26 Fructosamine and Glycated Albumin
- 10:50 Continuous Glucose Monitoring
- 15:44 The Overlooked Issue of Insulin Resistance
- 19:11 Summary
Show Notes
- On Measuring Glycemic Control:
- Hyperglycemia defines diabetes and drives microvascular disease, therefore we need to be able to accurately measure it.
- Many current techniques used for glucose measurement are flawed:
- Random glucose: A single snapshot in time which does not account for constant fluctuations
- Fasting glucose: Fails to capture postprandial hyperglycemia.
- Glucose tolerance test: Requires a tedious and intricate procedure that is not often routinely incorporate into daily practice.
- Hemoglobin A1C:
- Hemoglobin A1C = Hemoglobin bound to glucose in a concentration-dependent fashion
- Hemoglobin A1C is influenced primarily by two variables:
- Glucose Concentration: The diabetes measure we actually WANT.
- Duration of exposure of hemoglobin to glucose: UNRELATED to diabetes but is impacted primarily by the “lifespan” of a hemoglobin molecule.
- For the average person, one molecule of hemoglobin lasts 120 days in circulation, the same lifespan as an RBC.
- Any process that impacts RBC turnover will thus alter the average lifespan of an RBC in circulation.
- Increased RBC production→ More new, unglycated RBCs in circulation → falsely LOWERS A1C
- Can happen in hemolysis, bleeding, EPO administration, or after treatment of B12- iron-deficiency anemia.
- Decreased RBC production → More old, glycated RBCs in circulation→ falsely INCREASES A1C
- Can happen in iron deficiency, B12 deficiency, and diseases characterized by bone marrow failure.
- Glycated Proteins: An Alternative to Hemoglobin A1C:
- Two assays used in clinical practice:
- Fructosamine: a heterogeneous group of glycated proteins.
- Glycated albumin: exactly as the name suggests!
- Glycosylated protein measurement, like hemoglobin A1C, suffers from the similar flaw of being influenced both by glucose levels AND by its (protein) lifespan:
- States of protein loss, i.e, proteinuria, will result in increased protein production in the liver and decreased average circulating protein age, therefore falsely LOWER fructosamine levels.
- Continuous Glucose Monitors:
- Wearable device that measures glucose concentration every few minutes and can provide detailed data, including average, fasting, and post-prandial glucose.
- Superior to any other method for glycemic control measurement but often expensive and not adequately covered by insurance.
- CGM, as compared to usual care, has been shown to improve glycemic control in patients with Type 2 Diabetes on basal insulin.
- The Often Overlooked Issue of Hyperinsulinemia:
- Glycemic control can help reduce microvascular complications (retinopathy, neuropathy, nephropathy) of diabetes.
- Meanwhile, hyperinsulinemia and insulin resistance are associated with macrovascular/cardiovascular complications, whose rates are largely unaffected by achieving glucose control alone.
- Literature also suggests that hyperinsulinemia contributes to risk for cancer and Alzheimer’s disease
- Most of the traditional assays (random glucose, fasting glucose, A1c, glycated proteins, continuous glucose monitoring) discussed in this episode ONLY measure degree of hyperglycemia.
- The glucose tolerance test does help measure insulin resistance, but only indirectly. Again, it involves a tedious procedure often not performed in routine practice.
- Treating hyperinsulinemia involves lifestyle modification and possibly new pharmacological agents such as GLP1 agonists.
