Problematic hypoglycemia, defined as two or more episodes per year of severe hypoglycemia or as one episode associated with impaired awareness of hypoglycemia, extreme glycemic lability, ormajor fear andmaladaptive behavior, is a challenge, especially for patients with long-standing type 1 diabetes. Individualized therapy for such patients should include a composite target: optimal glucose control without problematic hypoglycemia. Therefore, we propose a tiered, four-stage algorithm based on evidence of efficacy given the limitations of educational, technological, and transplant interventions. All patientswith problematic hypoglycemia should undergo structured or hypoglycemia-specific education programs (stage 1). Glycemic and hypoglycemia treatment targets should be individualized and reassessed every 3-6 months. If targets are not met, one diabetes technologydcontinuous subcutaneous insulin infusion or continuous glucose monitoringdshould be added (stage 2). For patients with continued problematic hypoglycemia despite education (stage 1) and one diabetes technology (stage 2), sensor-augmented insulin pumps preferably with an automated low-glucose suspend feature and/or very frequent contact with a specialized hypoglycemia service can reduce hypoglycemia (stage 3). For patients whose problematic hypoglycemia persists, islet or pancreas transplant should be considered (stage 4). This algorithm provides an evidence-informed approach to resolving problematic hypoglycemia; it should be used as a guide, with individual patient circumstances directing suitability and acceptability to ensure the prudent use of technology and scarce transplant resources. Standardized reporting of hypoglycemia outcomes and inclusion of patients with problematic hypoglycemia in studies of new interventions may help to guide future therapeutic strategies.
Bibliographical noteFunding Information:
Funding. P.C. is supported in part by Diabetes UK grants 14/0004865 and 13/0005643.M.R.R. is supported in part by U.S. Public Health Service research grants R01-DK-091331 and U01-DK- 070430 from the National Institutes of Health. P.A.S. is supported by the Academic Alternate Relationship Plan and in part by Alberta Innovates Health Solutions and JDRF. M.-C.V. is supported by the French Ministry of Health (PHRC 2001, 2008, and 2009), European Community (Fond Euro?een de Developpement ? egional), Conseil ? egional Nord Pas de Calais (IFR 114), European FP7, JDRF, Soc?ete Francophone du Diabete, Association de Recherche pour le Diab ete, and Agence de Bio?edecine. T.W.K. is supported by the National Health and Medical Research Council (APP1037321), JDRF, Diabetes Australia Research Trust, Operational Infrastructure Support scheme of the Victorian Government, and Nationally Funded Centres scheme. F.S. is supported in part by Ministry of Health of the Czech Republic grant NT14020-3/2013. B.J.H. is supported in part by U.S. Public Health Service research grants U01- AI-065193 and U01-AI-102463 from the National Institutes of Health and by research grants 17- 2012-527 and 17-2013-495 from JDRF.