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Context: The effect of liraglutide in C-peptide-positive (C-pos) type 1 diabetes (T1D) patients during hypoglycemia remains unclear., Objective: To investigate the effect of a 12-week liraglutide treatment on the body glucose fluxes during a hypoglycemic clamp in C-pos T1D patients and its impact on the alpha- and beta-cell responses during hypoglycemia., Design: This was a randomized, double-blind, crossover study. Each C-pos T1D patient was allocated to the treatment sequence liraglutide/placebo or placebo/liraglutide with daily injections for 12 weeks adjunct to insulin treatment, separated by a 4-week washout period., Setting and Participants: Fourteen T1D patients with fasting C-peptide ≥ 0.1 nmol/L., Intervention(s): All patients underwent a hyperinsulinemic-stepwise-hypoglycemic clamp with isotope tracer [plasma glucose (PG) plateaus: 5.5, 3.5, 2.5, and 3.9 mmol/L] after a 3-month liraglutide (1.2 mg) or placebo treatment., Main Outcome Measure(s): The responses of endogenous glucose production (EGP) and rate of peripheral glucose disposal (Rd) were similar for liraglutide and placebo treatment during the clamp., Results: The numbers of hypoglycemic events were similar in both groups. At the clamp, mean glucagon levels were significantly lower at PG plateau 5.5 mmol/L in the liraglutide than in the placebo group but showed similar responses to hypoglycemia in both groups. Mean C-peptide levels were significantly higher at PG-plateaus 5.5 and 3.5 mmol/L after liraglutide treatment, but this effect was not reflected in EGP and Rd. Hemoglobin A1c and body weight were lower, and a trend for reduced insulin was seen after liraglutide treatment., Conclusions: The results indicate that 3 months of liraglutide treatment does not promote or prolong hypoglycemia in C-pos T1D patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To determine the effect of insulin on the resistance of subcutaneous tissue to the flow of infusion fluids., Materials and Methods: Thirty subjects with type 1 diabetes wore two Accu-Chek Spirit Combo insulin pumps with Accu-Chek FlexLink infusion sets (Roche Diabetes Care, Mannheim, Germany) for 7 days. One pump was filled with insulin aspart (Novo Nordisk, Bagsvaerd, Denmark) and used for continuous subcutaneous insulin infusion (CSII). The other pump was filled with insulin diluting medium (IDM; Novo Nordisk) and used to deliver IDM subcutaneously at rates identical to those employed for CSII. Both infusion sites were assessed daily by measuring the pressure required to infuse various bolus amounts of IDM., Results: On day 1, maximum pressure (P max ) and tissue flow resistance (TFR; calculated from measured pressure profiles) were similar for both infusion sites (P > 0.20). During the subsequent study days, the P max and TFR values observed at the IDM infusion site remained at levels comparable to those seen on day 1 (P > 0.13). However, at the site of CSII, P max and TFR progressively increased with CSII duration. By the end of day 7, P max and TFR reached 25.8 */2.11 kPa (geometric mean */geometric standard deviation) and 8.64 */3.48 kPa*s/μL, respectively, representing a remarkable 3.5- and 20.6-fold increase relative to the respective P max and TFR values observed on day 1 (P < 0.001)., Conclusion: Our results suggest that insulin induces a progressive increase in the resistance of subcutaneous tissue to the introduction of fluid; this has important implications for the future design of insulin pumps and infusion sets., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)