Introduction and Objective: The conventional hypoglycemic clamp utilizes high-dose IV insulin at fixed rates to induce target hypoglycemia, lacks standardized protocols and results in insulin overdose affecting spontaneous recovery. This improved hypoglycemic clamp procedure adjusts for individual insulin sensitivity and assesses “time to spontaneous recovery” as a critical endpoint.Methods: 12 healthy (41±12 yrs, 28±2 kg/m2) and 12 orally treated T2D subjects (58±4 yrs, 31±5 kg/m2, diabetes duration 9.5±5.6 yrs.) underwent 2 hypoglycemic clamps. After overnight monitoring, hypoglycemia was induced by variable IV insulin at 8:00 am to lower PG from 90 to 70 mg/dL (run-in). This was followed by a PG descent from 70 to 48 mg/dL (induction). At PG 48 mg/dL (nadir) insulin was stopped and glucose administered only if PG drops <48 mg/dL within the first 15 minutes. Time to spontaneous recovery (nadir to PG 70 mg/dl without rescue glucose) was assessed.Results: 47 out of 48 clamps achieved PG nadir and spontaneous recovery (fig.), one clamp was terminated early due to hypoglycemic symptoms. Mean (±SE) recovery time in healthy and T2D subjects was 28±2 and 37±2 min (p<0.01), respectively. Mean (±SE) total insulin dose to achieve nadir was 71±8 mU/kg in healthy and 183±19 mU/kg in T2D subjects (p<0.001).Conclusion: Our new clamp method safely reaches glucose nadir without rescue glucose, enabling “time to spontaneous recovery” to serve as a safety endpoint for novel therapies.
E. Svehlikova: None. W. Regittnig: None. G. Fluhr: None. M. Urschitz: None. D.A. Kraus: None. T.R. Pieber: Other – Speaker, Board member, Advisory panel; Current; Arecor. Research Support; Current; AstraZeneca. Other – Research support, Speaker, Board member, Advisory panel; Current; Eli Lilly and Company, Novo Nordisk, Sanofi. Employee; Current; CBmed – Center for Biomarker Research in Medicine.
IIS Grant by Eli Lilly (H60-NS-X003)
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