📘 Glycated hemoglobin (HbA1c)

Glycated hemoglobin (HbA1c) shows how much sugar has "stuck" to the hemoglobin in your red blood cells over the last three months. It's like a "black box" that continuously records all your blood glucose levels, not just the ones you measure yourself. The higher and longer your blood glucose has been, the more hemoglobin becomes irreversibly glycated.

HbA1c value is expressed in percentages (%) or mmol/mol. In people without diabetes it is below 5.6% (38 mmol/mol). For you, with type 1 diabetes, the target is below 7% (53 mmol/mol), individualized (higher or lower) by your doctor according to age and other conditions. HbA1c of 7% (53 mmol/mol) corresponds to an average blood glucose of approximately 154 mg/dl (8.6 mmol/L). Each 1% (11 mmol/mol) increase in HbA1c means approximately 30 mg/dl (1.7 mmol/mol) increase in average blood glucose.

Guidelines recommend HbA1c testing every three months if not already at target or if you have made treatment changes. Once you have stable treatment and are at target, you can reduce to two tests per year. Most diabetologists prefer to recommend quarterly testing for optimal monitoring under any conditions.

There's no point in testing more frequently than three months. Red blood cells generally live three months and this time is needed for their glycation to reflect changes in blood glucose evolution. In special situations (major treatment changes, preparation for surgical interventions), the doctor may request more frequent tests. The cost is reasonable and is usually covered by health insurance.

The standard target for most adults with type 1 diabetes is HbA1c below 7% (53 mmol/mol). This threshold generally offers the best balance between preventing complications and the risk of hypoglycemia. For children and adolescents, the target is also below 7% (53 mmol/mol), except for very young children where it might sometimes be below 7.5% (58 mmol/mol), if there is significant risk of hypoglycemia, with possible impact on brain development.

Your personal target may differ. It can be below 6.5% (48 mmol/mol) if you are young, without complications and without significant risk of hypoglycemia (approaching normal). A more relaxed target, below 8% (64 mmol/mol) may be recommended if you have severe frequent hypoglycemia, older age or advanced complications. During pregnancy you cannot rely on HbA1c values for metabolic control assessment. Discuss your individualized target with your doctor.

HbA1c reflects the overall average over three months, while daily blood glucose readings are snapshots of the moment. Attention! You can have good HbA1c, but very high glycemic variability, if you jump from 40 (2.2 mmol/L) to 300 mg/dl (16.7 mmol/L) and back often. Or you can have apparently good blood glucose when you test, but high HbA1c due to hyperglycemia you don't catch (e.g. at night or between glucometer tests).

HbA1c is influenced more by blood glucose from the last month (50% of value) compared to those from three months ago (10%). HbA1c does not detect hypoglycemia. It decreases slightly from them, but you can have excellent HbA1c with many dangerous hypoglycemic episodes. Therefore, interpretation requires more context. HbA1c is like a general average, and daily blood glucose like your individual grades.

Many conditions can affect HbA1c, independent of blood glucose. Iron deficiency anemia falsely increases HbA1c result, and hemolytic anemia decreases it. Hemoglobinopathies (thalassemia, sickle cell disease) interfere with measurement, generally giving falsely low values. Chronic renal insufficiency increases HbA1c through uremia, but dialysis lowers it.

Blood transfusions radically modify the result (false decrease). Pregnancy, rapid turnover of erythrocytes in very young children and some genetic variants of hemoglobin also give falsely low values. Discuss with your doctor if you have such conditions to use metabolic control assessment alternatives.

Yes, the HbA1c paradox! You can have HbA1c 7% (53 mmol/mol), both with stable blood glucose 90-150 mg/dl (5-8.3 mmol/L), and with extreme variability 40-300 mg/dl (2.2-16.7 mmol/L). The average can be the same, but the risk of complications differs greatly. High glycemic variability is associated with increased cardiovascular risk, for the same HbA1c.

Therefore, modern guidelines draw attention to assessing time in range 70-180 mg/dl (3.9-10 mmol/L) measured by a glucose sensor, in addition to HbA1c. The target is generally >70% time in range, below 4% time spent below 70 mg/dl (3.9 mmol/L) and below 25% above 180 mg/dl (10 mmol/L). Coefficient of variation below 36% indicates acceptable glycemic variability. HbA1c remains important, but as you can see it doesn't tell the whole story.

The simple formula for estimating average blood glucose is: Average (mg/dl) = 28.7 × HbA1c(%) - 46.7. Thus, average blood glucose according to HbA1c is approximately HbA1c 6% (42 mmol/mol) => 126 mg/dl (7 mmol/L); 7% (53 mmol/mol) => 154 mg/dl (8.6 mmol/L); 8% (64 mmol/mol) => 183 mg/dl (10.2 mmol/L); 9% (75 mmol/mol) => 212 mg/dl (11.8 mmol/L); 10% (86 mmol/mol) => 240 mg/dl (13.3 mmol/L).

Remember that this is the overall 24/7 average, including periods when you don't test (at night or between meals). It is not the arithmetic mean of your tests. The average of glucometer tests usually underestimates reality by 30 mg/dl (1.7 mmol/L), because you miss the peaks. For maximum accuracy, the glucose sensor provides the real average calculated from thousands of measurements.

The target below 7% (53 mmol/mol) comes from the classic DCCT study (done in 1993!) which demonstrated that maintaining HbA1c below 7% (53 mmol/mol) reduces at least by half the risk of chronic microvascular complications (retinopathy, nephropathy, neuropathy). The benefit persists even after several decades after relaxation of metabolic control as a result of the study's completion ("metabolic memory"). Patients from the intensive group have fewer complications even after 30 years from the intervention.

Each 1% (11 mmol/mol) reduction in HbA1c lowers the risk of complications by approximately 30%. The difference between 9% (75 mmol/mol) and 7% (53 mmol/mol) means reducing the risk by half! Below 7% (53 mmol/mol), the additional benefit exists but is smaller, and the risk of hypoglycemia increases greatly in the absence of a glucose sensor. Therefore 7% (53 mmol/mol) offers the best risk-benefit ratio for most patients.

Yes, very low HbA1c, below 6% (42 mmol/mol) in a patient on treatment with risk of hypoglycemia (sulfonylureas or insulin) may indicate frequent hypoglycemia, some possibly unrecognized. The ACCORD study showed increased cardiovascular risk with aggressive targeting below 6% (42 mmol/mol) in patients with type 2 diabetes on such treatment. For people with type 1 diabetes, HbA1c below 6.5% (48 mmol/mol) in the absence of using a glucose sensor is associated with tripling the risk of severe hypoglycemia.

There are some exceptions. During the honeymoon period or close to the onset of the LADA form of type 1 diabetes you can safely have nearly normal HbA1c due to good residual insulin production. With modern technology (sensors, advanced pumps with closed loop), some patients achieve HbA1c below 6.5% (48 mmol/mol) without significant hypoglycemia. Individual assessment with your doctor is essential.