HgbA1c (hemoglobin A1c) predicts prediabetes better than glucose

HgbA1c (hemoglobin A1c) is hemoglobin that has been ruined by glycation (bonding with sugar). It has long been recognized as a biomarker for average glucose over an approximately three month time span as well as a metric for the degree of damaging glycation occurring throughout the body. Now further evidence for its superior value as a predictor for prediabetes is presented in a study just published in The Lancet Diabetes & Endocrinology.The authors...

"...compared the risk of future outcomes across different prediabetes definitions based on fasting glucose concentration, HbA_1c, and 2 h glucose concentration during over two decades of follow-up in the community-based Atherosclerosis Risk in Communities (ARIC) study. We aimed to analyse the associations of definitions with outcomes to provide a comparison of different definitions."

HgbA1c compared to fasting and 2 hour glucose

They compared several prediabetes definitions in their ability to predict major long-term health problems. They analyzed data from over seven thousand subjects drawn from four communities across the USA who participated in the Atherosclerosis Risk in Communities (ARIC) study. HgbA1c was pitted against fasting and 2 hour postprandial glucose:

"Fasting glucose concentration and HbA_1c were measured at visit 2 and fasting glucose concentration and 2 h glucose concentration were measured at visit 4. We compared prediabetes definitions based on fasting glucose concentration (American Diabetes Association [ADA] fasting glucose concentration cutoff 5·6–6·9 mmol/L and WHO fasting glucose concentration cutoff 6·1–6·9 mmol/L), HbA_1c (ADA HbA_1ccutoff 5·7–6·4% [39–46 mmol/mol] and International Expert Committee [IEC] HbA_1c cutoff 6·0–6·4% [42–46 mmol/mol]), and 2 h glucose concentration (ADA and WHO 2 h glucose concentration cutoff 7·8–11·0 mmol/L)."

HgbA1c better identifies those at risk for diabetes and serious complications

Chronic kidney disease, cardiovascular disease and death were more accurately predicted by HgbA1c than by fasting glucose:

"After demographic adjustment, HbA_1c-based definitions of prediabetes had higher hazard ratios and better risk discrimination for chronic kidney disease, cardiovascular disease, peripheral arterial disease, and all-cause mortality than did fasting glucose concentration-based definitions (all p<0·05). The C-statistic for incident chronic kidney disease was 0·636 for ADA fasting glucose concentration clinical categories and 0·640 for ADA HbA_1c clinical categories. The C-statistics were 0·662 for ADA fasting glucose clinical concentration categories and 0·672 for ADA HbA_1c clinical categories for atherosclerotic cardiovascular disease, 0·701 for ADA fasting glucose concentration clinical categories and 0·722 for ADA HbA_1c clinical categories for peripheral arterial disease, and 0·683 for ADA fasting glucose concentration clinical categories and 0·688 for ADA HbA_1c clinical categories for all-cause mortality. Prediabetes defined using the ADA HbA_1c cutoff showed a significant overall improvement in the net reclassification index for cardiovascular outcomes and death compared with prediabetes defined with glucose-based definitions."

Clinical Significance

Medscape Family Medicine remarks:

"The researchers found that using an HbA_1c-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 HbA_1c."

The authors, quoted in Medscape Family Medicine, comment on the practical significance of their findings:

"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 A_1c 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."

The authors conclude:

"Our results suggest that prediabetes definitions using HbA_1c were more specific and provided modest improvements in risk discrimination for clinical complications. The definition of prediabetes using the ADA fasting glucose concentration cutoff was more sensitive overall."