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Insulin dose–response studies in severely insulin‐resistant type 2 diabetes—evidence for effectiveness of very high insulin doses
Author(s) -
Kampmann U.,
Hoeyem P.,
Mengel A.,
Schmitz O.,
Rungby J.,
Orskov L.,
Møller N.
Publication year - 2011
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2011.01373.x
Subject(s) - insulin , medicine , endocrinology , diabetes mellitus , crossover study , type 2 diabetes , insulin resistance , glucagon , placebo , alternative medicine , pathology
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.