Research in context
Evidence before this study
We searched the PubMed database up to May 9, 2016, using the search terms “continuous glucose monitoring”, “sensor-augmented pump therapy”, “low-glucose insulin suspension”, predictive low-glucose suspension”, “automated insulin pump suspension”, “threshold insulin pump interruption”, and “diabetes mellitus, type 1” for full reports of observational trials, randomised controlled trials and systematic reviews that investigated the effect of continuous glucose monitoring (CGM) on glycaemia in patients with type 1 diabetes and impaired awareness of hypoglycaemia. Our search identified one observational study and two randomised controlled trials. Findings from the observational study showed a reduction of severe hypoglycaemia in patients with impaired awareness of hypoglycaemia, reinforcing the need for randomised studies in patients with such impaired awareness. Investigators of one of the randomised trials reported improved hypoglycaemia awareness and glycaemic control from baseline to endpoint (24 weeks), which did not seem related to use of CGM, but was rather attributed to extensive interventions including weekly contact, monthly follow-up visits, and use of a bolus calculator to determine the insulin dose, whether or not an insulin pump was used. Moreover, sensors were used for a median of 57% of the time; only 17 of the 42 individuals achieved the 80% sensor usage threshold, which is often considered the frequency required for meaningful benefit. Findings from the second randomised controlled trial, which used CGM with low-glucose suspend, showed a reduction in severe hypoglycaemia in patients with impaired awareness of hypoglycaemia, but the population studied was quite young (mean age 18·6 years) and the reduction of severe hypoglycaemia lost significance when two outliers in the youngest age groups were excluded from the analysis. Since most patients with impaired awareness of hypoglycaemia are usually older than 40 years and have more than 25 years of diabetes duration, whether CGM adds any benefit (such as less hypoglycaemia and improved glycaemic control) in patients with impaired awareness of hypoglycaemia is still unknown.
Added value of this study
We report the findings from our randomised, crossover trial assessing the effect of CGM without low-glucose suspend on glycaemic control in adult patients with type 1 diabetes affected by impaired awareness of hypoglycaemia. CGM improved percentage of time patients spent in normoglycaemia compared with self-monitoring of blood glucose, by reducing both the percentage of time spent in hypoglycaemia and percentage of time spent in hyperglycaemia. Importantly, the results also showed CGM reduced severe hypoglycaemia in this typical population of patients with type 1 diabetes with impaired awareness of hypoglycaemia. In addition, the absence of an interaction between insulin treatment modality (multiple daily injections or continuous subcutaneous insulin infusion), and both the percentage of time spent in normoglycaemia and the proportion of patients affected by at least one severe hypoglycaemic event are of clinical importance.
Implications of all the available evidence
In earlier trials, CGM did not live up to the expectations of the diabetes community regarding its ability to reduce severe hypoglycaemia. However, our findings here support the benefit of CGM, both with and without combining it with continuous subcutaneous insulin infusion, for improving glycaemic control and diminishing severe hypoglycaemia in adult patients with type 1 diabetes and impaired awareness of hypoglycaemia, who are at highest risk of severe hypoglycaemia.