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Elevated Hemoglobin A1c Associated With Diabetes Within 4 Years

Aug 11, 2018

It is time to wake up and smell the coffee (roses) —  elevated hemoglobin A1c associated with diabetes, study finds; by providing free A1c tests at all check-ups we could find most of those with prediabetes.

There are 30 million people in the U.S. with diagnosed diabetes and close to 100 million with prediabetes who will most likely get diabetes in the near future, reduce their quality of life, and die years earlier than expected. The cost is now over 350 billion dollars to address this disease. What will the cost be when we triple the number of people diagnosed? The irony of this situation is that we can prevent or delay this from happening. As medical professionals, it is our responsibility to take the steps necessary to prevent this from happening for the medical and financial health of our country.


We know that by catching diabetes with an A1c of 5.7 to 6.4% (prediabetes) and with just a small amount of education on nutrition and physical activity we can prevent the majority of those 100 million people from getting or at least delaying the diagnosis of diabetes. This would improve the quality of life of those patients, extend their lives and probably save over 700 billion dollars.

Assessment of hemoglobin A1c (HbA1c) levels in addition to fasting glucose (FG) levels and other risk factors can improve diabetes risk assessment. Employee wellness programs (EWPs) are common in the U.S., providing opportunities to identify working-age individuals at risk for diabetes and to offer risk-reduction programs targeted to those at most risk. Based on the records of one large laboratory testing provider for EWPs, 25% of those offered FG testing were also offered HbA1c testing. Here we investigated whether the addition of HbA1c to FG testing for EWP participants with apparently normal FG (<100 mg/dL) would identify those at elevated risk for incident diabetes.

The analysis of this study was based on a cohort of 34,676 employees and spouses who participated in an EWP in 2012. Those with baseline FG ≥100 mg/dL, HbA1c ≥6.5% (48 mmol/mol), or a self-reported physician diagnosis of diabetes (n = 8,837), with missing baseline data (n = 244), or who failed to participate in the EWP at least once during 4 years of follow-up (n = 4,256) were excluded, leaving 21,339 participants. The association between baseline HbA1c levels and incident diabetes (FG ≥126 mg/dL or a self-reported physician diagnosis of diabetes in any annual follow-up EWP) was assessed in regression models that adjusted for age, sex, FG, triglyceride–to–HDL cholesterol ratio, serum creatinine, alanine aminotransferase, BMI, and blood pressure.

In this population of individuals not diagnosed with diabetes with normal FG, 513 participants had incident diabetes during 4 years of follow-up. Those with incident diabetes were older (46.1 ± 9.9 years) than those without incident diabetes (43.7 ± 11.0 years; P = 3 × 10−7). Of the 85% of participants who reported their ethnicity, 49% reported white, 17% Asian, 13% African American, 12% Hispanic, and 9% other. The cumulative rate of incident diabetes after median follow-up of 3.96 years was 0.74 (95% CI 0.68 to 0.80) per 100 person-years (cumulative incidence of 3.0%, 95% CI 2.7 to 3.2, at 4 years of follow up). Baseline HbA1c levels were associated with incident diabetes.  Similar results were observed after further adjustment for ethnicity.

Those with the highest 5% of HbA1c values had 8.4-fold greater risk of diabetes than those with normal HbA1c levels. At the end of follow-up, the diabetes-free survival rate was 0.84 for those with HbA1c >5.9% (41 mmol/mol) but <6.5% (48 mmol/mol), and 0.98 for those with normal HbA1c levels.

Odds of incident diabetes according to HbA1c level.

Although EWP data were available for those who participated at baseline or during follow-up, no effort was made to contact the ∼16.6% of participants who did not participate in any follow-up EWP. It was noted that because a variety of genetic, ethnic, behavioral, or medical factors can disrupt the correlation between average blood glucose levels and HbA1c, the possibility of false-negative risk assessment can be reduced by using both HbA1c and FG levels to assess diabetes risk. Although this analysis focused on the use of HbA1c to identify diabetes risk among those with normal FG levels, recently HbA1c levels have been combined with BMI and other modifiers of diabetes risk in risk prediction models that have been developed in two large community-based, U.S.-based population studies.

From the results, it was concluded that among those with normal FG levels, some will progress to diabetes within four years, but HbA1c levels can be used to identify some of those at the highest risk of progression so that appropriate prevention efforts can be directed to this small but important group.

Practice Pearls:

  • By providing free A1c tests at all check-ups and at drugstores with an advertising campaign, we could identify more people who have prediabetes.
  • With a small amount of basic education on nutrition and physical activity, we could extend life and improve quality of life of people who have prediabetes.
  • The medical savings would pay for any costs involved in identifying people who have prediabetes.

Diabetes Care 2018 Apr; dc172500. https://doi.org/10.2337/dc17-2500