Design, management and completion of the hypoCOMPaSS RCT evaluating potential for restoration of hypoglycaemia awareness in type 1 diabetes using conventional vs novel technologie : and exploration of potential phenotypes predicting persistent impaired awareness despite study intervention

Abstract

Aim: To explore the extent to which impaired awareness of hypoglycaemia (IAH) can be improved using currently available treatment regimens in individuals with long-standing type 1 diabetes mellitus (T1DM), and to characterise those individuals whose awareness of hypoglycaemia did not improve. Methods: A multicentre, 2x2 factorial 24-week RCT (HypoCOMPaSS) comparing multiple daily injections (MDI) and continuous subcutaneous insulin infusion therapy (CSII) with or without real-time continuous glucose monitoring (RT) in a population with T1DM and IAH was designed. The study was undertaken in five UK centres using established and novel outcome measures to assess hypoglycaemia awareness, glycaemic control and treatment satisfaction. A second analysis was undertaken characterising individuals within the HypoCOMPaSS population as responders and non-responders. Complication status, autonomic symptom profile and hyperglycaemia avoidance scores were assessed. Results: Overall, hypoglycaemia awareness improved, and biochemical hypoglycaemia, severe hypoglycaemia rate and insulin doses reduced without deterioration in HbA1c. There were no significant differences in awareness comparing MDI with CSII; and RT with conventional glucose monitoring. Between-group analyses demonstrated comparable reductions in severe hypoglycaemia, biochemical hypoglycaemia, fear of hypoglycaemia and insulin doses with equivalent HbA1c. Treatment satisfaction was highest with CSII. In the second study there was a suggestion that longer diabetes duration and increased age may impair ability to respond to the interventions but this did not correlate with severity of autonomic symptoms. Conclusions: Hypoglycaemia awareness can be improved and recurrent severe hypoglycaemia prevented in long-standing T1DM without relaxing HbA1c. Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII / RT. All individuals may benefit from biomedical interventions to improve awareness of hypoglycaemia. This ii research provides a basis for further studies investigating impact of new technologies on severe hypoglycaemia and underlines the importance of tailoring treatment to avoid biochemical hypoglycaemia without relaxing overall control.