Long-term glycemic instability increases risk of microvascular damage in T1DM

Kilpatrick ES et al. (2008) A1c variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care 31: 2198–2202

Whether fluctuations in blood-glucose levels influence the incidence of microvascular complications in patients with type 1 diabetes (T1DM) is a controversial topic. An analysis of data from the Diabetes Control and Complications Trial (DCCT) suggests that long-term glycemic instability increases the risk of retinopathy and nephropathy in such patients.

The DCCT was a 9-year study that compared the effects of conventional and intensive glycemic control on the development of microvascular complications in 1,441 diabetic individuals. Kilpatrick et al. examined variability in quarterly HbA_1c measurements as an indicator of glycemic instability. HbA_1c variability was higher in conventionally treated patients than in those treated intensively. Whether measured as updated HbA_1c, SDs of HbA_1c levels across all follow-up visits, or an updated, time-dependent SD, variability was an independent predictor of retinopathy and nephropathy: every 1% increase in the HbA_1c SD was associated with a hazard ratio of 2.26 for development of retinopathy, and 1.80 for nephropathy. A patient whose HbA_1c variability was in the 97.5^th centile had more than three times the risk of developing retinopathy, and more than twice the risk for nephropathy, of a patient whose variability was in the 2.5^th centile.

The authors conclude that, in contrast to the apparent lack of effect of short-term (daily) changes in blood glucose, long-term fluctuations in serum HbA_1c levels increase the risk of microvascular complications in patients with T1DM. Regular measurements of HbA_1c levels might help to monitor at-risk patients.