Haemoglobin A1c (HbA1c) encompasses the integrated value of blood glucose fluctuations over three months and has been employed as a standard monitoring system for diabetes control by health care professionals.
Many clinical trials, e.g., DCCT (1), have shown its efficacy in depicting long-term complications of diabetes and its good correlation with average blood glucose levels.
This test principle involves non-enzymatic glycosylation (i.e., irreversible binding of glucose to proteins) of hemoglobin in red blood cells (with a life span of 90-120 days), the rate of the reaction being proportional to the levels of ambient blood glucose levels.
Glucose diffuses freely into RBC and attaches to a specific moiety of hemoglobin (Hb), forming a specific sub-fraction (HbA1c) measured by various methods.
It doesn’t require a fasting state, has greater precision and pre-analytic stability, and offers more convenience to the patients and doctors.
On the downside,
- It suffers from its inability to account for acute blood glucose changes
- Being expensive
- Limited use in special conditions like hemoglobinopathies
- Pregnancy
- Aging and chronic kidney disease.
HbA1c in Diagnosis and follow-up
It has been used in the diagnosis and subsequent follow-up of diabetic patients successfully.
HbA1c reading can be used to diagnose people with prediabetes and diabetes. The information in the chart below shows normal HbA1c Levels (Range)
| HbA1c* values | Interpretation(2) |
|---|---|
| ≤5.6% | Normal |
| 5.7-6.4% | Pre-Diabetes |
| ≥6.5% | Diabetes |
*measured by High-performance liquid chromatography certified to conform to NGSP (National glycohemoglobin standardization programme) of DCCT trial.
In patients with diabetes, the target HbA1c goal recommended by most guidelines is 6.5 – 8%, depending upon the variables like:
- Duration of diabetes
- Life expectancy
- Comorbidities (like cardiovascular disease, obesity, hyperlipidemia)
- Age group
- Risk of hypoglycemia
The stringent target (6.5 %) is advised for recently diagnosed patients who are:
- Young
- Comorbid free with a life expectancy of more than 30 years
Relaxed target (8 %) is recommended for:
- Elderly frail patients with a limited life expectancy
- Hypoglycemia unawareness
- Multiple comorbidities.
Nevertheless, an HbA1c target of <7% is endorsed by the majority of guidelines for most nonpregnant individuals.
HbA1c Targets in Pregnancy
- HbA1c is physiologically lowered by 0.5% due to expansion of red blood cell (RBC) mass and recruitment of new immature RBCs.
- Diffusion of glucose through the RBC membrane increases with age, so the build-up of newer RBCs lowers HbA1c values in pregnancy.
- A target of <6% is optimal, and < 6.5% is acceptable in most pregnant females; the rationale is that the incidence of congenital fetal anomalies is similar to non-diabetic females at these levels.
- Poorly controlled patients (HbA1c of > 8.5 – 9.5%) are prone for fetal cardiac,central nervous system and gut anomalies.
- Inspite of its shortcomings, HbA1c is recommended every 2-3 months in pregnant females for monitoring.
HbA1c Targets in Children
In children with diabetes, similar HbA1c targets (6.5 – 7.5%) are appropriate, personalized by taking into account:
- The access to insulin analogs and CGMS (continuous glucose monitoring system)
- Hypoglycemia risk
- Complications
- Frequency of blood glucose monitoring and too young to articulate age.
HbA1c is an excellent validated tool to evaluate the medium-term risk of diabetes complications, but it is plagued by racial and ethnic differences, glycemic variability, and other biological variables.
Recently, CGMS has evolved as a better glucose monitoring system and might supersede HbA1c as a preferred method in the near future.
CGM metrics like time in range (TIR), above (TAR) and below range (TBR), glucose management index (estimated HbA1c), and low and high glucose alerts are established adjunctive measures that empower both patients and health care professionals in the effective management of diabetes.
