Hemoglobin A1C (HbA1c) shows a complex relationship with mortality that follows a U-shaped or J-shaped curve, where both very low and very high levels are associated with increased death risk.

Low HbA1c was associated with increased all-cause mortality among adults without diabetes.

Low hemoglobin A1c (<4.0%) is associated with an increased risk of all-cause mortality .

This may be related to underlying conditions affecting red blood cell turnover, nutritional deficiencies, or chronic.

Hemoglobin A1c (HbA1c) is strongly associated with all cause and cardiovascular disease in both diabetic and non-diabetic populations.

The lowest mortality risk is generally seen with HgbA1C levels between 6.5% and 7:5%, while both higher and lower HbA1c levels are associated with increased mortality risk.

Specifically, HbA1c levels above 8% are consistently linked to higher all-cause and cardiovascular mortality, with risk rising further as HbA1c increases above 9%.

HgbA1C as a prognostic marker for mortality risk, and underscore the importance of individualized glycemic targets, especially in older adults and those with comorbidities.

The optimal HbA1c range for minimizing mortality appears to be 6.0-7.0% and 5.0%-6.0% in non-diabetic individuals.

However, aggressive lowering of HbA1c below these ranges may not confer additional benefit and could increase risk, particularly in older or frail patients

Elevated HbA1c levels (particularly >9%) are well-established risk factors for mortality in people with diabetes, associated with complications like cardiovascular disease, kidney disease, and other diabetic complications.

The relationship between hemoglobin A1c and cardiovascular disease and all-cause mortality is continuous and significant throughout the whole distribution , meaning risk increases progressively rather than having distinct thresholds.

The optimal HbA1c range appears to be around 5.0-6.4% for non-diabetic individuals and 6.5-8.0% for many people with diabetes, though individual targets should consider age, comorbidities, and life expectancy.

The optimal intensity of glucose control in older adults with diabetes remains uncertain: both excessively tight and poor glycemic control can be harmful, supporting individualized treatment targets rather than one-size-fits-all approaches.

In patients with type 2 diabetes, higher HbA1c levels are associated with an increase in mortality risk.

Individuals with a time-updated mean HbA1c ≥9.7% have a substantially higher hazard ratio for all-cause and cardiovascular death compared to those with HbA1c ≤6.9%.

This risk gradient is most pronounced in younger patients but persists across all age groups.

Conversely, excessively low HbA1c levels may also be associated with increased mortality, likely reflecting comorbidities or overtreatment.

There is a stepwise increase in mortality risk with higher HbA1c, especially in younger patients.

Higher HbA1c levels are associated with increased mortality, and optimal survival is generally observed with HbA1c in the range of 6–7% for most adults with diabetes.

Individualization of glycemic targets remains important, particularly in older adults and those with comorbidities.

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