HbA1c Better Than Glucose for Predicting Prediabetes Risk

Veronica Hackethal, MD

November 22, 2016

Using HbA1c to diagnose prediabetes may improve identification of people at risk for major health complications over the next 10 years, according to the latest analysis from the community-based Atherosclerosis Risk in Communities (ARIC) study, published online November 15 in Lancet Diabetes & Endocrinology.

"The goal is to figure out who is at the highest risk of not only developing diabetes but of developing its serious complications, including kidney disease, cardiovascular disease [CVD], and even death. Hemoglobin A1c appears to be the tool that is best able to do that," commented first author Bethany Warren, a PhD student at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, in a press release from her institute.

This analysis is the first to formally compare several prediabetes definitions and how well they can predict major long-term health problems.

Lack of Consensus About Exact Definition of Prediabetes

Prediabetes affects roughly 12% to 30% of US adults, although getting an accurate estimate has been difficult because of lack of consensus about the exact definition of prediabetes, which is also sometimes called "intermediate hyperglycemia." Not all patients with prediabetes go on to develop type 2 diabetes.

The American Diabetes Association (ADA) recommends a fasting glucose cutoff of 100 to 125 mg/dL, an HbA1c cutoff of 5.7% to 6.4%, or a 2-hour glucose-concentration cutoff of 140 to 199 mg/dL. The World Health Organization (WHO) recommends the same 2-hour glucose concentration cutoff as the ADA but stipulates a higher fasting glucose cutoff of 110 to 125 mg/dL to indicate prediabetes. Meanwhile, the International Expert Committee (IEC) recommends an HbA1c cutoff of 6.0% to 6.4% to identify those at intermediate risk of diabetes.

Participants in the ARIC study included middle-aged adults from four communities in North Carolina, Mississippi, Minnesota, and Maryland. Participants were followed for over 2 decades.

The researchers followed 10,844 people who had fasting glucose concentrations and HbA1c measured between 1990 and 1992 and 7194 people who had fasting and 2-hour glucose concentrations measured between 1996 and 1998.

Then they compared how well prediabetes definitions using ADA, WHO, and IEC cutoffs predicted 10-year risk for incident diabetes, chronic kidney disease, CVD, peripheral arterial disease, and all-cause mortality..

Results showed that the ADA and IEC HbA1c and WHO fasting glucose cutoffs identified fewer people with prediabetes than the ADA fasting glucose and ADA and WHO 2-hour glucose-concentration cutoffs.

For example, using the ADA fasting glucose-concentration cutoff, 38% of people in the study had prediabetes, compared with 19% with the ADA HbA1c cutoff.

The HbA1c cutoffs generally yielded higher relative risk for long-term health complications than the glucose-concentration cutoffs.

The researchers found that using an HbA1c-based definition, those identified as having prediabetes were 50% more likely to develop kidney disease, twice as likely to develop CVD, and 60% more likely to die from any cause compared with those with normal HbA1c.

To estimate whether the findings may generalize to a larger population, researchers did an additional analysis using National Health and Nutrition Examination Survey (NHANES) data, which showed similar results.

Consensus on Prediabetes Would Help Target Highest-Risk People

The authors note that knowing which cutoffs better predict long-term health outcomes may help organizations reach a consensus prediabetes definition, which could improve earlier identification of the disorder.

That, in turn, could help best target the people who could benefit from earlier interventions, such as lifestyle modification and medication, which could slow progression to diabetes.

"When someone is told they have prediabetes, we hope it will cause them to make changes to their habits in order to prevent the development of diabetes and its complications," added the study's senior author, Elizabeth Selvin, PhD, MPH, a professor in the Bloomberg School's department of epidemiology.

"Being identified as having prediabetes can also make it easier to receive weight-loss and nutritional counseling as well as reimbursement for these services. Intensive lifestyle changes and weight loss can reduce the risk of diabetes, so it is critically important we identify those persons who are at high risk.

"At the same time, we also don't want to overdiagnose people. Using the hemoglobin A1c test allows us to more accurately identify those persons at highest risk," she added.

"This is important information for physicians and it is also important information for professional organizations. Coming to a global consensus on how to define and diagnose prediabetes would really help move the field forward — and help patients all over the world," she concluded.

Ms Warren had no relevant financial relationships. Dr Selvin received grants from the National Institute of Diabetes and Digestive and Kidney Diseases for this study, as well as grants from the National Institutes of Health (NIH) and the Foundation for the NIH unrelated to this work. Disclosures for the coauthors are listed in the article.

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Lancet Diabetes Endocrinol. Published online November 15 2016. Abstract

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