HbA1c

HbA1c and Mortality Risk: Understanding Optimal Ranges

Glycated hemoglobin (HbA1c) is an important marker for average blood glucose levels over the previous 2-3 months. Recent research has revealed a complex relationship between HbA1c levels and mortality risk, with optimal ranges varying based on diabetes status and other factors. This report examines the current evidence on HbA1c ranges and their association with mortality risk.

The Shape of the Relationship: J-Curve or U-Curve

Multiple studies have identified a non-linear relationship between HbA1c and mortality risk:

A significant J-shaped relationship has been observed between HbA1c and all-cause mortality¹²
For individuals with diabetes, the relationship between HbA1c and mortality follows a U-shaped curve³
This non-linear pattern indicates increased mortality risk at both low and high extremes of HbA1c levels⁴

This pattern challenges the traditional "lower is better" approach to glycemic control, suggesting there are both upper and lower thresholds for safe HbA1c levels.

Optimal HbA1c Ranges by Population

For People With Diabetes

Research indicates different optimal ranges for individuals with diabetes:

The optimal HbA1c level range for patients with diabetes is 5.6% to 7.4%⁴
In Korean patients with Type 2 diabetes, the lowest mortality rate was observed at HbA1c levels of 6.5-6.9%⁵
For older adults with diabetes, an HbA1c <8.0% is associated with reduced risk of mortality⁶
For cardiovascular disease patients with diabetes, an optimal HbA1c target value of 6.9% was identified³

For People Without Diabetes

For individuals without diagnosed diabetes, different optimal ranges apply:

The optimal HbA1c range for those without diabetes is 5.0% to 6.5%⁴
Using 5.0% to 5.4% as the reference range, both lower (<4.0%) and higher (>5.5%) HbA1c levels were associated with increased mortality risk⁷

Specific Mortality Risks at Different HbA1c Levels

Low HbA1c Levels

Very low HbA1c levels are associated with increased mortality:

HbA1c <4.0% was associated with a nearly three-fold higher risk of all-cause mortality (HR 2.90) compared to 5.0-5.4% in individuals without diabetes⁷
For people with diabetes, a 1% increase in HbA1c when below 7.5% was associated with a 10% reduction in mortality risk (RR 0.90)¹²
In CVD patients with diabetes, HbA1c below 6.2% showed higher mortality risk compared to 6.2-6.8%³

High HbA1c Levels

Elevated HbA1c also increases mortality risk:

Each 1% increase in HbA1c above 7.5% was associated with a 4% higher mortality risk (RR 1.04)¹²
For older adults with diabetes, HbA1c 8.0-8.9% and ≥9.0% had hazard ratios of 1.6 and 1.8 for mortality, respectively⁶
Among people without known diabetes, mortality risk rises steeply for HbA1c levels above 5.7%⁸

Special Populations

Older Adults

For older adults with diabetes, HbA1c >8.0% was associated with increased all-cause and cause-specific mortality⁶
This suggests that while tight glycemic control may not be appropriate for all older adults, very high HbA1c levels should be avoided

Cardiovascular Disease Patients with Diabetes

Among CVD patients with diabetes, the relationship between HbA1c and mortality is U-shaped³
HbA1c levels of 6.2-6.8% were associated with the lowest mortality risk in this population (HR 0.49 compared to <6.2%)³

Conclusion

The evidence consistently shows a J-shaped or U-shaped relationship between HbA1c and mortality risk. This suggests the existence of an optimal "security zone" for HbA1c levels, with increased mortality at both high and low extremes.

For people with diabetes, the optimal range appears to be approximately 5.6% to 7.4%, with the lowest risk often observed around 6.5-6.9%. For those without diabetes, the optimal range is approximately 5.0% to 6.5%.

These findings have important clinical implications, suggesting that individualized HbA1c targets may be more appropriate than a one-size-fits-all approach to glycemic control, particularly for older adults and those with comorbidities.