Continuous Glucose Monitoring for Hypoglycemia Avoidance and Glucose Counterregulation in Long Standing Type 1 Diabetes.

Context: Patients with long-standing type 1 diabetes (T1D) are at increased risk for severe hypoglycemia because of defects in glucose counterregulation and recognition of hypoglycemia symptoms, in part mediated through exposure to hypoglycemia. Objective: To determine whether implementation of real-time continuous glucose monitoring (CGM) as a strategy for hypoglycemia avoidance could improve glucose counterregulation in patients with long-standing T1D and hypoglycemia unawareness. Design, Setting, Participants, and Intervention: Eleven patients with T1D disease duration of similar to 31 years were studied longitudinally in the Clinical & Translational Research Center of the University of Pennsylvania before and 6 and 18 months after initiation of CGM and were compared with 12 nondiabetic control participants. Main Outcome Measure: Endogenous glucose production response derived from paired hyperinsulinemic stepped-hypoglycemic and euglycemic clamps with infusion of 6,6-H-2(2)-glucose. Results: In patients with T1D, hypoglycemia awareness (Clarke score) and severity (HYPO score and severe events) improved (P < 0.01 for all) without change in hemoglobin A(1c) (baseline, 7.2% +/- 0.2%). In response to insulin-induced hypoglycemia, endogenous glucose production did not change from before to 6 months (0.42 +/- 0.08 vs 0.54 +/- 0.07 mg.kg(-1).min(-1)) but improved after 18 months (0.84 +/- 0.15 mg.kg(-1).min(-1); P < 0.05 vs before CGM), albeit remaining less than in controls (1.39 +/- 0.11 mg.kg(-1).min(-1); P <= 0.01 vs all). Conclusions: Real-time CGM can improve awareness and reduce the burden of problematic hypoglycemia in patients with long-standing T1D, but with only modest improvement in the endogenous glucose production response that is required to prevent or correct low blood glucose.