Despite advances in the pharmacological and technical fields, the risk of hypoglycemia remains the major concern for the regulation of optimal blood sugar levels in type 1 diabetes. there is an increasing interest in how the opposing actions of insulin and glucagon (Gn) may be harnessed to optimize glycemic control.
For the purpose, Bruce W. Bode from Atlanta, GA, and colleagues studied 11 T1D patients (age 36±4y, gender M:F 5:6, BMI 25.0±0.7 kg/m2, disease duration 23±3y, A1C 7.0±0.3%, daily insulin dose 43±3u) on two occasions, under meal challenge conditions (liquid mixed meal, 100g carbohydrate) during a phased 6h IV regular insulin infusion with (+Gn) and without (-Gn) IV glucagon. On both occasions, subjects were treated overnight with low dose IV insulin prior to the morning meal to prevent antecedent nocturnal hypoglycemia and to attain near-normal fasting glycemia.
Insulin dosing was designed to control the early rise in plasma glucose (PG) but also to elicit hypoglycemia in the later phase.
Key findings of the study include:
- During +Gn, glucagon was co-administered with insulin at a fixed molar ratio. At the two visits, fasting PG was similar (-Gn 121±5, +Gn 119±6 mg/dl) and the initial meal-induced PG elevation (0-3h) was indistinguishable whether glucagon was present or not (peak PG -Gn 224±18, +Gn 228±15 mg/dl; ΔPG 0-180AUC -Gn 10501±3014, +Gn 11537±1778 mg.min/dl).
- During the latter phase (3-6h), 7/11 -Gn subjects experienced an excessive fall in PG to <80mg/dl with 5/11 dropping to 50mg/dl requiring IV glucose rescue (by protocol).
- During +Gn, the fall in PG was attenuated in all cases with a significant difference observed in PG nadir (-Gn 51.1±4.0, +Gn100.5±11.0 mg/dl).
- Appropriate elevations in plasma insulin and glucagon were observed in keeping with study design.
"To conclude, it is feasible that insulin and glucagon can be co-administered under specific conditions allowing protection against insulin-induced hypoglycemia without impeding hyperglycemic control. This unique observation offers insight into novel approaches to glucose control in diabetes," wrote the authors.
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