Association of Long-Term Change and Variability in Glycemia with Risk of Incident Heart Failure among Patients with Type 2 Diabetes Mellitus – A Secondary Analysis of the ACCORD Trial

Objective: Evaluate the associations between long-term change and variability in glycemia with risk of HF among patients with T2DM.

Research Design and Methods: Among participants with T2DM enrolled in the ACCORD trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV=average absolute difference between successive values), coefficient of variation (CV=standard deviation/mean), and standard deviation. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of % change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF.

Results: The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF [HR (95% CI) for ≥10% decrease = 1.32 (1.08-1.75), ≥10% increase = 1.55 (1.19-2.04), ref: <10% change in HbA1c]. Higher long-term variability in HbA1c was significantly associated with higher risk of HF [HR (95% CI) per 1 SD of ASV = 1.34 (1.17-1.54)] independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed using alternative measures of glycemic variability.

Conclusions: Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.