Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS)

Abstract

OBJECTIVETo determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODSA 24-week 2 3 2 factorial randomized controlled trial in adults with type 1 diabetes and IAH was conducted. All received comparable education, support, and congruent therapeutic targets aimed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control. Primary end point was between-intervention difference in 24-week hypoglycemia awareness (Gold score). RESULTSA total of 96 participants (mean diabetes duration 29 years) were randomized. Overall, biochemical hypoglycemia (£3.0 mmol/L) decreased (53 6 63 to 24 6 56 min/24 h; P = 0.004 [t test]) without deterioration in HbA 1c . Hypoglycemia awareness improved (5.1 6 1.1 to 4.1 6 1.6; P = 0.0001 [t test]) with decreased SH (8.9 6 13.4 to 0.8 6 1.8 episodes/patient-year; P = 0.0001 [t test]). At 24 weeks, there was no significant difference in awareness comparing CSII with MDI (4.1 6 1.6 vs. 4.2 6 1.7; difference 0.1; 95% CI 20.6 to 0.8) and RT with SMBG (4.3 6 1.6 vs. 4.0 6 1.7; difference 20.3; 95% CI 21.0 to 0.4). Between-group analyses demonstrated comparable reductions in SH, fear of hypoglycemia, and insulin doses with equivalent HbA 1c . Treatment satisfaction was higher with CSII than MDI (32 6 3 vs. 29 6 6; P = 0.0003 [t test]), but comparable with SMBG and RT (30 6 5 vs. 30 6 5; P = 0.79 [t test]). CONCLUSIONSHypoglycemia awareness can be improved and recurrent SH prevented in longstanding type 1 diabetes without relaxing HbA 1c . Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT, although satisfaction was higher with CSII.

A randomized controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with Type 1 diabetes and impaired awareness of hypoglycaemia

“…The lack of improvement in Gold score with CGM is consistent with findings seen in the IN CONTROL study 15 and in a retrospective audit 19. The HypoCOMPaSS study showed that restoration of hypoglycaemia awareness can be achieved, but that self‐monitoring capillary blood glucose and CGM have an equivalent effect on impaired awareness of hypoglycaemia 20. However, the study designs and technologies implemented differ, and further research is warranted to explore the impacts of technology as an adjunct to education in people with Type 1 diabetes and impaired awareness of hypoglycaemia.…”

Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes

“…CGM was not associated with an improvement in IAH or SH in this study. 38 Wong et al, assessed CGM use in the T1D exchange registry. Of the 1662 participants reporting CGM use at enrollment into the registry, 675 (41%) reported discontinuing CGM after 1 year.…”

Response to Comment on Little et al. Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS). Diabetes Care 2014;37:2114–2122

“…Uninterrupted RT-CGM was advocated in our trial (3), but only 17% achieved .80% sensor usage (2), which provides evidence of likely real-world use with this iteration of the technology in unselected adults with IAH. This is in contrast to published efficacy studies, where those with SH have typically been excluded and only those prepared to wear sensors for the majority of the time were allowed to participate (5)d precluding extrapolation to real-world practice.…”

“…We do not agree that education, weekly telephone contact, and monthly visits (as part of a targeted 6-month intervention for those with impaired awareness of hypoglycemia [IAH]) should be dismissed as unachievable. We have shown the potential for a .10-fold reduction in severe hypoglycemia (SH)dincluding in those patients not receiving more costly technological interventions (2). Moreover, given increasing availability of bolus calculators on both handheld glucometers and cell phone apps, there is no reason why access should be limited to those using continuous subcutaneous insulin infusion (CSII) or real-time continuous glucose monitoring (RT-CGM).…”