Restoration of Self-Awareness of Hypoglycemia in Adults With Long-Standing Type 1 Diabetes

Abstract

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 232 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- mic increased (mean 6 SE from 2.6 6 0.1 to 3.1 6 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420–780] vs. 710 [460–1,260], P = 0.02; metanephrine, 2,412 [23,026 to 7,279] vs. 5,180 [2771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONSdEven in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.