Insulin dose response studies in severely insulin resistant type 2 diabetes - evidence for effectiveness of very high insulin doses

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. Materials and Methods: We included 8 insulin resistant (mean insulin dose: 186 IU/d. BMI: 35) subjects with type 2 diabetes in a single-blinded, randomised crossover study. Each subject was studied on two occasions. On each occasion subjects underwent two 3-h hyperinsulinaemic euglycaemic clamps. The subjects were randomised 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 (GIR) were accomplished and we observed a clear dose response relation with GIR values of 0.4 ±0.2 (SE), 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 800 IU/d, suggesting effectiveness of very high insulin doses in severely insulin resistant subjects.