HbA1c variability and the risk of microvascular complications in type 1 diabetes: data from the DCCT

Abstract

Objective There remains debate as to whether short or long-term glycemic instability confers a risk of microvascular complications which is in addition to that predicted by mean glycemia alone. This study has analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of HbA_1c variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes.

Research Design and Methods HbA_1c was collected quarterly during the DCCT in 1441 individuals. The mean HbA_1c and the standard deviation (SD) of HbA_1c variability following stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy having adjusted for age, gender, disease duration, treatment group, and baseline HbA_1c.

Results Multivariate Cox regression showed that variability in HbA_1c added to mean HbA_1c in predicting the risk of development or progression in both retinopathy (HR=2.26 for every 1% increase in HbA_1c SD, 95% CI 1.63-3.14, p<0.0001) and nephropathy (HR=1.80, 95% CI 1.37-2.42, p<0.0001), with the relationship especially a feature in conventionally treated patients.

Conclusions This study has shown that variability in HbA_1c adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer term fluctuations in glycemia seem to be contributory to the development of retinopathy and nephropathy in type 1 diabetes.