Restoration of Self-awareness of Hypoglycemia in AdultsWith Long-standing Type 1 Diabetes Hyperinsulinemic-hypoglycemic clamp substudy results from the

OBJECTIVEdImpaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restora-tion of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoid-ance in adults with T1D with IAH (Gold score $4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN ANDMETHODSdEighteen subjects with T1D and IAH (mean6 SD age 50 6 9 years, T1D duration 35 6 10 years, HbA1c 8.1 6 1.0 % [65 6 10.9 mmol/mol]) underwent stepped hyperinsulinemic hypoglycemic clamp studies before and after a 6-month in-tervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 23 2 factorial study design, tomultiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continu-ous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTSdAfter intervention, glucose concentrations at which subjects first felt hypoglyce