Why a key diabetes test may work differently depending on your race

A test widely used to diagnose and monitor diabetes may vary in accuracy based on your race and other factors, potentially influencing how aggressively your doctor monitors and treats your diabetes.

The hemoglobin A1c test measures the average level of sugar, or glucose, attached to a protein in your red blood cells called hemoglobin. The test gauges that average over the previous three months or so.

Yet scientists have long speculated that hemoglobin A1c levels can vary depending on your race or genetics, which could interfere with your test results and lead health care providers to think your blood sugar is higher or lower than it really is.

People of African, Mediterranean or Southeast Asian descent are particularly at risk of interference, according to the National Institute of Diabetes and Digestive and Kidney Diseases. People who have family members with sickle cell anemia or an inherited blood disorder called thalassemia also can be at risk.

A new study of patients with type 1 diabetes looked into such interference, specifically for black patients. The study, published in the journal Annals of Internal Medicine on Monday, suggests that hemoglobin A1c levels can overestimate the average glucose concentration in black patients, compared with white patients.

This overestimate could lead a doctor to target a black patient’s blood sugar levels aggressively, causing dangerously low blood sugar.

“I believe our study, for the first time, definitively shows there is a component of higher A1c that is due to biologic or genetic differences in glucose attaching to the red blood cell,” said Dr. Richard Bergenstal, executive director of the International Diabetes Center in Minneapolis and lead author of the study.

The study notes that race only partially explains the hemoglobin A1c differences, and more research is needed to identify social and economic factors that may influence blood sugar levels in various groups of people.

For black patients in America, who have traditionally faced a history of barriers and disadvantages in health care, those factors might also include having limited access to care or medications.

Bergenstal offered one specific question that concerned patients could ask their doctors: “Are we depending just on the hemoglobin A1c to measure how my diabetes control is doing, or are we actually looking at the blood sugars to get a little better reflection of my blood sugars?”

He added that “the A1c, you know, is kind of an average marker, and no patient is average. One of our take-home messages is, it’s probably time to be looking at blood sugars and personalizing therapy for each individual a little more than just this average blood sugar test.”

Many US adults who have diabetes don’t know it

Diabetes is a disease in which your blood sugar levels are above normal, which could cause health problems. With type 1 diabetes, your pancreas does not make insulin, a hormone that helps glucose get into your cells to give them energy. Type 2 diabetes results primarily from your body’s ineffective use of insulin.

Globally, the number of people with type 1 and type 2 diabetes has climbed from 108 million in 1980 to 422 million in 2014, according to the World Health Organization.

About 60 million people are living with diabetes in the European region, according to the WHO. More than 29 million Americans are living with diabetes, according to the US Centers for Disease Control and Prevention.

In the US, type 2 accounts for about 95% of all diagnosed cases of diabetes. Type 1 diabetes, which occurs most often in children and young adults but can appear at any age, accounts for about 5%.

Up to 25% of American adults who have diabetes don’t even know that they have it or that they could be developing potentially serious complications (PDF).

High hemoglobin A1c levels tend to correlate with complications, Bergenstal said.

“Glucose attaching on to proteins in the eye, kidney, nerve and blood vessels may be one way diabetes with high glucose is part of the cause of complications – like blindness, kidney disease and nerve disease and amputations,” he said.

Small racial difference identified in type 1 diabetes patients

The new study included data on 104 black patients and 104 white patients with type 1 diabetes. The data were taken from 10 diabetes centers across the US between October 2015 and January of 2017.

The hemoglobin A1c was measured in each patient at the start of the study and then at four, eight and 12 weeks out. Each patient’s glucose concentrations also were monitored using a research version of Abbott Diabetes Care’s FreeStyle Libre Pro flash glucose monitoring system.

Bergenstal has received grants from and served on consulting/advisory boards for Abbott Diabetes Care, as well as other health-care companies, including Novo Nordisk, Becton Dickinson, Boehringer Ingelheim, Bristol-Myers Squibb/AstraZeneca, and Johnson & Johnson, during the conduct of the study.

The researchers found that the average hemoglobin A1c levels in black patients were higher than those in white patients, with a difference of about 0.8 percentage points. Based on the average glucose concentrations in the patients, however, the difference should have been only about 0.4 percentage points, the researchers found.

Yet the study came with limitations.

“We didn’t study type 2, but I think there’s no reason to think the pathophysiology or the chemistry of how glucose attaches to red cells is any different in type 2 than type 1,” Bergenstal said.

“We just studied non-Hispanic African-Americans,” he added. “We did not study Asians or Native Americans or Hispanics to see if there is a difference from whites, but we have a good model of how to test that in the future.”

Other diabetes researchers also have called for more research, but not necessarily with a focus on race.

Is personalized medicine the future of diabetes care?

The new study calls for more focus on personalized medicine, taking into account a patient’s ethnic background as well as other factors, said Dr. Alvin Powers, president of medicine and science for the American Diabetes Association and a professor at the Vanderbilt University School of Medicine.

“The A1c is an important measurement that the person with diabetes should know and should monitor with his or her health care provider, because if the A1c is elevated, your chance of having diabetes-related complications increases,” said Powers, who was not involved in the new study.

Patients with diabetes can reduce the risk of complications by keeping an A1c level below 7% as a goal, according to the American Diabetes Association.

“So, moving the A1c as close to the goal determined by the patient and his or her doctor is important, but this study shows that in interpreting the A1c, there may be some variation, whether an individual is of African-American descent or of Caucasian descent,” Powers said.

Though interesting, the new study findings should be interpreted with caution and not necessarily be applied clinically until more research is conducted, said Dr. Leonard Egede, a professor of medicine at the Medical College of Wisconsin, who was not involved in the study.

“The key thing is that when you look at racial differences, we have social factors, clinical factors, and we also have what some people would consider genetic factors. I think the social and environmental factors are larger contributors to differences than the genetic factors,” Egede said. “When you look at what they’re describing, the idea that glucose variability may differ … I don’t think that’s enough to neglect the fact that we actually have major issues around access to care, quality of care, access to medications.”

He added that the study “should not detract from the core message we’ve been trying to get across to patients, which is that they need to take ownership of their disease, and they need to be very aggressive in their diet, their physical activity and taking their medication.”

Elizabeth Selvin, a professor at Johns Hopkins Bloomberg School of Public Health, and David Sacks, a researcher at the National Institutes of Health, co-authored an editorial published alongside the new study.

All in all, “these findings suggest next steps for the field,” they wrote.

“We should seek to better understand subgroups that may be prone to discordant HbA1c and glucose measures; such groups may overlap with race, but we should not conflate such conditions with race itself,” they wrote. “Ultimately, the results of this study suggest that race is a poor surrogate for underlying causes of disease risk. To improve patient care, we need to understand the major causes of disparities in measures of hyperglycemia,” also known as high blood sugar.