Can smoking cause discordance between Hemoglobin A1c (HbA1c) and glucose levels, particularly with an HbA1c of 8.0% and a Continuous Glucose Monitoring (CGM) estimated HbA1c of 6.1%?

From the Guidelines

Smoking can indeed cause discordance between HbA1c and glucose readings, and in this case, with an HbA1c of 8.0% and a CGM estimated HbA1c of 6.1%, a thorough workup is recommended to determine the cause of this discrepancy. The initial step should include fructosamine and glycated albumin tests, which reflect shorter-term glucose control (2-3 weeks) compared to HbA1c's 3-month average, as suggested by 1. Complete blood count should be ordered to check for hemolytic anemia, along with iron studies, vitamin B12, and folate levels to rule out nutritional anemias. Hemoglobin electrophoresis is important to identify hemoglobinopathies that can affect HbA1c accuracy. Liver and kidney function tests should be included since organ dysfunction can alter HbA1c values, as noted in 1 and 1.

The discordance occurs because smoking increases carbon monoxide levels in the blood, which binds to hemoglobin and artificially elevates HbA1c readings without affecting actual glucose levels. Additionally, smoking causes oxidative stress that can accelerate glycation of hemoglobin independent of glucose levels. In this situation, the CGM data may provide a more accurate reflection of actual glycemic control, and treatment decisions might need to be based more heavily on glucose monitoring rather than HbA1c alone, as recommended by 1.

Some key points to consider in this case include:

• The importance of using CGM and SMBG data to adjust treatment and prevent hypoglycemia, as emphasized in 1 and 1
• The need to assess individual readiness to use CGM technology and provide ongoing education and support, as noted in 1
• The limitations of HbA1c as a measure of glycemic control, particularly in individuals with conditions that affect red blood cell turnover or hemoglobin variants, as discussed in 1
• The potential benefits of using other measures of average glycemia, such as fructosamine and 1,5-anhydroglucitol, to provide a more complete picture of glycemic control, as suggested by 1.

Overall, a comprehensive approach is necessary to determine the cause of the discordance between HbA1c and glucose readings in this patient, and to develop an effective treatment plan that takes into account the potential effects of smoking on glycemic control.

From the Research

Discordance between HbA1c and Glucose Levels

• The discordance between Hemoglobin A1c (HbA1c) and glucose levels can occur due to various factors, including the presence of certain medical conditions or the use of certain medications 2, 3, 4.
• A study published in 2017 found that there is no statistical correlation between HbA1c and continuous glucose monitoring (CGM)-assessed glucose levels in patients with HbA1c >8.0% 3.
• Another study published in 2021 found that 50% of patients had HbA1c-GMI differences ≥0.5% and 22% had differences ≥1%, indicating substantial discordance between laboratory and estimated HbA1c in a real-world setting 2.
• A 2024 study found that up to 29% of participants had a discordance between HbA1c and GMI of <0.5%, with 22% having a discordance between 0.5% and 1%, and 49% having a discordance of >1% in patients with diabetes and end-stage kidney disease treated by hemodialysis 4.

Factors Affecting HbA1c and Glucose Levels

• Advanced chronic kidney disease (estimated glomerular filtration rate <60) can increase discordance between laboratory and estimated HbA1c 2.
• Hemolytic anemia can result in falsely low HbA1c values, making it a poor marker for overall glycemia in diabetic patients with hemolytic disease 5.
• Time in range (TIR) can be used as an intermediate metric to estimate HbA1c, with a strong correlation between TIR and HbA1c in patients with type 1 diabetes 6.

Specific Scenario

• In the case of an HbA1c of 8.0% and a CGM-estimated HbA1c of 6.1%, the discordance between the two values may be due to various factors, including the presence of certain medical conditions or the use of certain medications 3.
• The lack of correlation between HbA1c and CGM-assessed glucose levels in patients with HbA1c >8.0% may also contribute to the discordance in this scenario 3.