Interventions That Restore Awareness of Hypoglycemia in Adults With Type 1 Diabetes: A Systematic Review and Meta-analysis

OBJECTIVE Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia (SH) sixfold and affects 30% of adults with type 1 diabetes (T1D). This systematic review and meta-analysis looks at the educational, technological, and pharmacological interventions aimed at restoring hypoglycemia awareness (HA) in adults with T1D. RESEARCH DESIGN AND METHODS We searched The Cochrane Library, MEDLINE, Embase, Science Citation Index Expanded, Social Sciences Citation Index, PsycINFO, and CINAHL from inception until 1 October 2014. Included studies described HA status at baseline. Outcome measures were SH rates, change in HA, counterregulatory hormone responses, and glycemic control. RESULTS Forty-three studies (18 randomized controlled trials, 25 before-and-after studies) met the inclusion criteria, comprising 27 educational, 11 technological, and 5 pharmacological interventions. Educational interventions included structured diabetes education on flexible insulin therapy, including psychotherapeutic and behavioral techniques. These were able to reduce SH and improve glycemic control, with greater benefit from the latter two techniques in improving IAH. Technological interventions (insulin pump therapy, continuous glucose monitoring, and sensor-augmented pump) reduced SH, improved glycemic control, and restored awareness when used in combination with structured education and frequent contact. Pharmacological studies included four insulin studies and one noninsulin study, but with low background SH prevalence rates. CONCLUSIONS This review provides evidence for the effectiveness of a stepped-care approach in the management of patients with IAH, initially with structured diabetes education in flexible insulin therapy, which may incorporate psychotherapeutic and behavioral therapies, progressing to diabetes technology, incorporating sensors and insulin pumps, in those with persisting need.