Greater HbA1c variability is associated with increased cardiovascular events in type 2 diabetes patients with preserved renal function, but not in moderate to advanced chronic kidney disease

Abstract

Emerging evidence suggests that glycemic variability may be a more reliable measure of glycemic control than mean HbA1c in type 2 diabetes mellitus. This study aimed to determine if HbA1c variability is associated with cardiovascular events in type 2 diabetic patients and if different renal functions affect such association. This longitudinal study enrolled 8259 diabetic patients from the Kaohsiung Medical University Research Database in 2009 and were followed-up until 2015. Intra-individual HbA1C variability was defined as the standard deviation (SD) of HbA1c and cardiovascular events were defined as hospitalization for coronary artery disease, unstable angina, myocardial infarction, stroke, peripheral artery disease, and cardiovascular death. The patients were grouped into two based on their estimated glomerular filtration rate (eGFR) ≥ 60 or < 60 min/ml/1.73m2. In a mean follow-up period of 6.3 years, cardiovascular events were recorded in 8.9% of the patients. In an adjusted Cox model, high HbA1c SD (hazard ratio, 1.290; 95% confidence interval, 1.008–1.650; p = 0.043), but not mean HbA1c, was associated with significantly increased risk of cardiovascular events in patients with eGFR ≥ 60 min/ml/1.73m2. This association was not seen in patients with eGFR < 60 min/ml/1.73m2. In this study, greater HbA1c variability is associated with increased risk of cardiovascular among patients with preserved renal function, but not in those with moderate to advanced chronic kidney disease.

Fasting plasma glucose variability and HbA1c are associated with peripheral artery disease risk in type 2 diabetes

“…Several potential mechanisms may link glycemic variability to the occurrence of PAD from a pathophysiological point of view. First, evidence has suggested that oscillating glucose may trigger increases in oxidative stress, endothelial dysfunction or damage, advanced glycation end-products and inflammatory cytokines, resulting in a higher rate of occurrence and acceleration of atherosclerosis independently of sustained hyperglycemia [12][13][14][28][29][30][31][32][33]. Second, A relationship of cardiovascular autonomic dysfunction with atherosclerosis has been observed [34,35].…”

Prognostic impact of HbA1c variability on long-term outcomes in patients with heart failure and type 2 diabetes mellitus

“…Nevertheless, a few studies have investigated the long-term effect of variability in HbA1c [ 29 ]. As a whole, most agree that glycemic variability predicts all-cause mortality, fatal or non-fatal CVD in T2DM [ 30 – 34 ]. However, there were opposing reports for these outcomes, the RIACE study revealed that HbA1c variability did not have a major effect on macrovascular complications including coronary or cerebrovascular events, myocardial infarction, or stroke [ 35 ].…”

Effect of mean HbA1c on the association of HbA1c variability and all‐cause mortality in patients with type 2 diabetes

“…Beck et al proposed that estimation of glycaemic control using HbA1c alone may not be accurate for some patients . Recently, the relationships of HbA1c variability with diabetic complications and mortality in patients with T2D have piqued research interest. A recent study reported that the association of mean HbA1c with all‐cause mortality disappeared after adjustments for HbA1c variability measures, suggesting that HbA1c minimally influences all‐cause mortality.…”