Incidence of severe hypoglycemia and possible associated factors in pediatric patients with type 1 diabetes in the real-life, post-Diabetes Control and Complications Trial setting: A systematic review

Background/Objective: In 1993, the Diabetes Control and Complications Trial (DCCT) found that intensive antihyperglycemic therapy was effective in the primary and secondary prevention of microvascular complications in patients with type 1 diabetes (T1D) but was associated with a 3-fold greater rate of severe hypoglycemia (SH) than conventional therapy. The aim of this analysis was to determine whether, in the real-world setting, the incidence of SH in pediatric patients with T1D has changed since 1993. Methods: A systematic literature search of PubMed for prospective or retrospective observational studies (≥250 participants) on SH epidemiology or related topics in pediatric patients with T1D, published between October 1993 and June 2016, identified 35 articles (involving >55 000 participants). SH incidence data were analyzed in approximate 5-year blocks: 1993-2000, 2001-2005, 2006-2010, and 2011-2016. Information on factors that might influence the incidence of SH was also collected. Results: A trend for a marked reduction in the incidence of SH in the post-DCCT setting (from 62.0 per 100 patient-years to 1.21-30 per 100 patient-years) was apparent. Factors that could have influenced this temporal trend in SH incidence included the increased use of new types of, and methods of administering, insulin, in particular rapid-acting insulin analogs and continuous subcutaneous insulin infusion. Conclusions: SH in pediatric patients with T1D has declined in incidence since the DCCT but remains a common problem. The optimal use of new insulin therapies/regimens/technologies, improved education, and dedicated specialized management teams are needed to help reduce the risk of SH in this population.