title: Evidence-informed clinical practice recommendations for treatment of type 1 diabetes complicated by problematic hypoglycemia.
abstract: 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, or major fear and maladaptive 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 patients with 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 technology-continuous subcutaneous insulin infusion or continuous glucose monitoring-should 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.
authors.affiliation: Diabetes Research Group, King's College London, London, U.K.
authors.forename: Pratik
authors.initials: P
authors.lastname: Choudhary
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
authors.affiliation: Department of Medicine, Division of Endocrinology, University of Alberta, Edmonton, Canada.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Senior
authors.affiliation: Endocrinology and Metabolism Department, INSERM U1190, European Genomics Institute for Diabetes, Lille University Hospital, Lille Cedex, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Vantyghem
authors.affiliation: Diabetes Research Institute, Scientific Institute Ospedale San Raffaele, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Maffi
authors.affiliation: Immunology and Diabetes Unit, St. Vincent's Institute, University of Melbourne, Melbourne, Australia.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kay
authors.affiliation: Diabetes Clinic and Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
authors.affiliation: Department of Diabetes and Clinical Nutrition, Kyoto University, Kyoto, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Saudek
authors.affiliation: Department of Endocrinology and Diabetology, University of Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Lehmann
authors.affiliation: Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN bhering@umn.edu.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Hering
mesh_terms: D000465:Algorithms; D001364:Awareness; D001786:Blood Glucose / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D019317:Evidence-Based Medicine; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D016035:Pancreas Transplantation; D010353:Patient Education as Topic / Q000379:methods
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin