HbA1c Variability in First Two Years After Diabetes Diagnosis Helps Predict CVD Risk

An analysis of 29k patients with type 2 diabetes suggests increased HbA1c variability within the first 2 years of a diabetes diagnosis was associated with a 30-59% increase in risk of incident cardiovascular disease.

An analysis of data from the landmark LEAD study is offering further insight into the increase in risk of cardiovascular disease associated with increased levels of HbA1c variability among patients with type 2 diabetes.

Using data from more than 29,000 patients from Louisiana, investigators found patients with type 2 diabetes and the highest levels of HbA1c variability were at a 59% increased risk of incident cardiovascular disease compared to their counterparts with the lowest level of variability.

“The underlying mechanism for the relationship between wide variations in blood sugar levels between doctor’s appointments and high risk of heart disease in patients with type 2 diabetes is unclear,” said Gang Hu, MD, MPH, PhD, an associate professor and director of the Chronic Disease Epidemiology Lab at Pennington Biomedical Research Center at LSU, in a statement. “It’s possible that episodes of severely low blood sugar may be the connection.”

Interested in how visit-to-visit glycemic variability might impact risk of cardiovascular disease among patients with type 2 diabetes, the current study was designed as a retrospective cohort study using electronic health record data from January 1, 2013 to April 30, 2018 within the Louisiana Experiment Assessing Diabetes outcomes (LEAD) cohort study. From the study, investigators identified a cohort of 29,260 patients with at least 4 HbA1c measurements obtained within the first 2 years following a diagnosis of type 2 diabetes.

The study cohort had a mean age of 66.3±12.5 years, 40.6% (n=11,868) were African American, and 45.9% (n=13,430) were men. From LEAD, investigators obtained information related to participants’ age at diabetes diagnosis, race/ethnicity, BMI, blood pressure, cholesterol levels, tobacco use, eGFR, and medication use, which were used as covariates in final analyses.

For the purpose of analysis, investigators designed Cox proportional hazards regression models to assess risk of cardiovascular disease according to quartiles of HbA1c standard deviation (SD), HbA1c coefficient of variability (CV), and adjusted HbA1c SD. Mean HbA1c values were 6.3±0.7%, 6.7±0.8%, 7.5±1.1%, 8.6±1.5% for the first, second, third, and fourth quartile, respectively (P <.001).

During a mean follow-up of 4.18, investigators identified a total of 3746 incident cardiovascular disease events. In adjusted analyses, results demonstrated increased risk for incident cardiovascular disease among each increasing quartile of HbA1c variability, with the second, third, and fourth quartiles at a 30% (95%, 40% (HR, 1.40; 95% CI, 1.26-1.55) (HR, and 59% (HR, 1.59; 95% CI, 1.41-1.77) increase in risk, respectively, when compared to the first quartile (P for trend <.001). Additionally, similar results were observed in analyses using HbA1c CV and adjusted HbA1c SD as exposures.

Further analysis indicated HbA1c variability was also associated with increased risk of first and recurrent severe hypoglycemic events. Investigators noted results suggested severe hypoglycemia could have a mediating effect on the association of HbA1c variability and increased risk of cardiovascular disease.

“We recommend that patients and their doctors implement therapies that can reduce wide swings in blood sugar levels and the associated episodes of severe low blood sugar,” added Dr. Hu. “Our findings suggest that measuring the swings in blood hemoglobin A1c levels over a specific time – six months to a year, for example – could serve as a supplemental blood sugar target.”

This study, “Association between visit-to-visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes,” was published in Diabetes, Obesity & Metabolism.