Insulin Delivery Into the Peripheral Circulation: A Key Contributor to Hypoglycemia in Type 1 Diabetes

• DOI: 10.2337/db15-0071
• Publication Date: 2015-06-18T02:20:39Z
• Authors: Justin M. Gregory; Guillaume Kraft; Melanie F. Scott; Doss W. Neal; Ben Farmer; Marta S. Smith; Jon R. Hastings; Eric J. Allen; E. Patrick Donahue; Noelia Rivera; Jason J. Winnick; Dale S. Edgerton; Erica Nishimura; Christian Fledelius; Christian L. Brand; Alan D. Cherrington
• Keywords: Insulin delivery; Circulation (fluid dynamics)

Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, was infused into hepatic Po or a peripheral (Pe) at rate four times of basal. protocol 1, full counterregulatory response allowed, whereas 2, glucagon fixed basal, mimicking diminished α-cell hypoglycemia seen T1DM. glucose fell faster with Pe than insulin, reaching 56 ± 3 vs. 70 6 mg/dL (P = 0.04) 60 min. The change area under curve (ΔAUC) for similar between and Po, but peak occurred earlier Pe. ΔAUC epinephrine greater (67 17 36 14 ng/mL/180 min). also more rapidly 41 67 2 < 0.01) by Without rise glucagon, responses were much larger (ΔAUC 204 22 96 29 min Po). summary, exacerbates hypoglycemia, particularly presence response. delivery, mimic (i.e., liver-preferential analogs), should therefore