AIM: To combat diabetic complications strict glycaemic control is desirable in type 2 diabetes, but some patients are severely insulin resistant and it is not known whether high doses of insulin are effective. This study was designed to determine the acute dose-response effects of insulin in patients with type 2 diabetes and severe insulin resistance. METHODS: We included eight insulin-resistant (mean insulin dose: 186 IU/day; body mass index: 35) subjects with type 2 diabetes in a single-blinded, randomized crossover study. Each subject was studied on two occasions. On each occasion, subjects underwent two 3-h hyperinsulinaemic euglycaemic clamps. The subjects were randomized to two low-dose insulin infusions (0.5 and 1.5 mU/kg/min in random order) on one occasion and to two high-dose insulin infusions (3.0 and 5.0 mU/kg/min in random order) on another occasion. RESULTS: On all occasions, steady-state glucose infusion rates (SSGIRs) were accomplished and we observed a clear dose-response relationship with GIR values of 0.4 ± 0.2 (s.e.), 2.6 ± 0.6, 3.7 ± 0.8 and 4.9 ± 0.9 mg/kg/min during the 0.5, 1.5, 3.0 and 5.0 mU/kg/min insulin infusions, respectively (p < 0.001). Likewise, there was a dose-dependent suppression of endogenous glucose production (EGP) (p < 0.009), plasma free fatty acids (FFAs) (p < 0.001) and plasma glucagon (p = 0.001). CONCLUSIONS: Our results show that the insulin dose response in terms of GIR and EGP is preserved for insulin doses corresponding to >800 IU/day, suggesting effectiveness of very high insulin doses in severely insulin-resistant subjects.
RCT Entities:
AIM: To combat diabetic complications strict glycaemic control is desirable in type 2 diabetes, but some patients are severely insulin resistant and it is not known whether high doses of insulin are effective. This study was designed to determine the acute dose-response effects of insulin in patients with type 2 diabetes and severe insulin resistance. METHODS: We included eight insulin-resistant (mean insulin dose: 186 IU/day; body mass index: 35) subjects with type 2 diabetes in a single-blinded, randomized crossover study. Each subject was studied on two occasions. On each occasion, subjects underwent two 3-h hyperinsulinaemic euglycaemic clamps. The subjects were randomized to two low-dose insulin infusions (0.5 and 1.5 mU/kg/min in random order) on one occasion and to two high-dose insulin infusions (3.0 and 5.0 mU/kg/min in random order) on another occasion. RESULTS: On all occasions, steady-state glucose infusion rates (SSGIRs) were accomplished and we observed a clear dose-response relationship with GIR values of 0.4 ± 0.2 (s.e.), 2.6 ± 0.6, 3.7 ± 0.8 and 4.9 ± 0.9 mg/kg/min during the 0.5, 1.5, 3.0 and 5.0 mU/kg/min insulin infusions, respectively (p < 0.001). Likewise, there was a dose-dependent suppression of endogenous glucose production (EGP) (p < 0.009), plasma free fatty acids (FFAs) (p < 0.001) and plasma glucagon (p = 0.001). CONCLUSIONS: Our results show that the insulin dose response in terms of GIR and EGP is preserved for insulin doses corresponding to >800 IU/day, suggesting effectiveness of very high insulin doses in severely insulin-resistant subjects.
Authors: Stefan Korsatko; Sigrid Deller; Gerd Koehler; Julia K Mader; Katharina Neubauer; Charlotte L Adrian; Henrik Thomsen; Hanne Haahr; Thomas R Pieber Journal: Clin Drug Investig Date: 2013-07 Impact factor: 2.859
Authors: Jean Farup; Jesper Just; Frank de Paoli; Lin Lin; Jonas Brorson Jensen; Tine Billeskov; Ines Sanchez Roman; Cagla Cömert; Andreas Buch Møller; Luca Madaro; Elena Groppa; Rikard Göran Fred; Ulla Kampmann; Lars C Gormsen; Steen B Pedersen; Peter Bross; Tinna Stevnsner; Nikolaj Eldrup; Tune H Pers; Fabio M V Rossi; Pier Lorenzo Puri; Niels Jessen Journal: Cell Metab Date: 2021-10-21 Impact factor: 31.373
Authors: Ulla Kampmann; Ole N Mathiassen; Kent L Christensen; Niels H Buus; Mette Bjerre; Henrik Vase; Niels Møller; Anne Kaltoft; Per L Poulsen Journal: J Diabetes Res Date: 2017-09-07 Impact factor: 4.011