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Pediatr Diabetes. 2019 Jun 8. doi: 10.1111/pedi.12876. [Epub ahead of print]

Incidence of severe hypoglycemia and possible associated factors in pediatric patients with type 1 diabetes mellitus in the real-life, post-DCCT setting: a systematic review.

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"G. Salesi" Hospital, Department of Women's and Children's Health, Azienda Ospedaliero-Universitaria, Ancona, Italy.
Department of Paediatrics, University of Turin, Italy.
Department of Human Pathology, University of Messina, Italy.
Diabetes Business Unit, Eli Lilly, Sesto Fiorentino, Italy.
CORESEARCH, Centre for Outcomes Research and Clinical Epidemiology, Pescara, Italy.



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 mellitus (T1DM) but was associated with a 3-fold greater rate of severe hypoglycemia (SH) than conventional therapy.


To determine whether, in the real-world setting, the incidence of SH in pediatric patients with T1DM has changed since 1993.


A systematic literature search of PubMed for prospective or retrospective observational studies (≥250 participants) on SH epidemiology or related topics in pediatric patients with T1DM, 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.


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.


SH in pediatric patients with T1DM 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. This article is protected by copyright. All rights reserved.


Diabetes mellitus, type 1; hypoglycemia; pediatrics; review, systematic


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