Dose--response characteristics for effects of insulin in patients with type 2 diabetes and severe insulin resistance: evidence for the utility of high doses of insulin
Ulla Kampmann1, Pernille Høyem1, Anette Mengel1, Lotte Ørskov2 & Niels Møller1
Background: To avoid the serious complications of diabetes glucose control must be tackled aggressively in type 2 diabetes. However some patients with type 2 diabetes are severely insulin resistant and although they are treated with large doses of insulin their blood glucose is still not optimally controlled.
Aim: This project aims to determine the doseresponse to insulin in patients with type 2 diabetes and severe insulin resistance.
Design and methods: The study is a single-blinded, randomized crossover study. We included eight individuals with type 2 diabetes treated with more than 100 IU insulin/day. The study protocol was reviewed and approved by the regional ethical committee. To assess the doseresponse to insulin the hyperinsulinemiceuglycemic clamp method was used. The patients were studied on two occasions. On each occasion the patients were given two sequential infusions of insulin at two different rates, each for 3 h. Each patient was thus given four different doses of insulin (0.5, 1.5, 3.0 and 5.0 mU/kg per min).
Results: On average our patients were treated with 186 IU insulin/day, ranging from 106 to 264 IU/day.
The mean exogenous glucose infusion rates over the last 30-min period during the 0.5, 1.5, 3.0, and 5.0 mU/kg per min insulin infusions were 0.4±0.2 (S.E.M.), 2.6±0.6, 3.7±0.8, and 4.9±0.9 mg/kg per min, respectively.
Conclusion: Our results show that patients with severe insulin resistance respond to insulin treatment, and even at very high insulin doses (5.0 mU/kg per min), a doseresponse effect is maintained. It therefore seems reasonable to increase insulin doses in patients with severe insulin resistance in order to obtain optimal metabolic control.