Relating mean blood glucose and glucose variability to the risk of multiple episodes of hypoglycaemia in type 1 diabetes

Aims/hypothesis The main disadvantage of intensive treatment in the Diabetes Control and Complications Trial (DCCT) was an increased risk of hypoglycaemia that was not explained by the difference in HbA₁c values alone. This study re-analysed DCCT data to establish whether mean blood glucose (MBG) and/or glucose variability add to the predictive value of HbA₁c for hypoglycaemia risk in type 1 diabetes. Methods The times to first and subsequent severe hypoglycaemic events were compared with MBG, HbA₁c and within-day SD of blood glucose using Cox regression after adjusting for other known risk factors for hypoglycaemia. Results On its own, the incidence of time to first hypoglycaemic event increased 1.05-fold for each 1 mmol/l decrease in MBG and 1.07-fold for every 1 mmol/l increase in glucose SD. MBG and SD of blood glucose also both added to the ability of HbA₁c to predict repeated hypoglycaemic events: after adjusting for HbA₁c, a 1 mmol/l increase in SD was associated with a 1.09-fold increased risk of a first event, increasing to a 1.12-fold risk of a fifth event. A 1 mmol/l fall in MBG added a constant 1.02-1.03-fold risk of repeated events. Daytime events were predicted more accurately than nocturnal episodes. Conclusions/interpretation This study has established that HbA₁c, MBG and glucose variability measurements each have an independent role in determining an individual's risk of hypoglycaemia in type 1 diabetes. All three aspects of glycaemic assessment should thus be considered in patients in whom hypoglycaemia is a real or potential problem.