M-J J Pouwels1, C J Tack, A R Hermus, J A Lutterman. 1. Division of General Internal Medicine, Department of Medicine, University Medical Centre Nijmegen, Nijmegen, The Netherlands. m.j.pouwels@club.tip.nl
Abstract
AIMS: Despite high-dose s.c. insulin therapy, some Type 2 diabetes mellitus (DM) patients remain in poor metabolic control. We investigated whether a period of euglycaemia using i.v. insulin, followed by continuous subcutaneous insulin infusion (CSII), would ameliorate the deleterious effects of hyperglycaemia on insulin sensitivity and result in sustained, improved metabolic control. METHODS: In a prospective observational study, eight Type 2 DM patients with severe insulin resistance (insulin dose 1.92 +/- 0.66 U/kg per day (mean +/-sd)), in poor metabolic control (HbA(1c) 12.0 +/- 1.7%), were treated with i.v. insulin for 31 +/- 10 days aimed at euglycaemia, followed by CSII therapy for 12 months, using insulin lispro. Before and after 28 +/- 6 days of i.v. insulin treatment, insulin sensitivity was measured by a hyperinsulinaemic euglycaemic clamp. RESULTS: Euglycaemia was reached after 12 +/- 6 days of i.v. insulin treatment. Subsequently, the i.v. insulin dose required to maintain euglycaemia decreased from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg per day (P < 0.005). Whole body glucose uptake increased from 12.7 +/- 5.7 to 22.4 +/- 8.8 micromol/kg per min (P < 0.0005). HbA(1c) decreased to 8.9 +/- 1.2% after 28 +/- 6 days, to 7.1 +/- 0.6% after 6 months and to 8.3 +/- 1.4% after 12 months (P < 0.001 vs. pretreatment, for all). Lipid profile improved and plasminogen activator inhibitor type 1 levels decreased significantly. Mean body weight did not change. CONCLUSIONS: In Type 2 diabetic patients, who are poorly controlled despite high-dose s.c. insulin treatment, a period of 2 weeks of euglycaemia achieved by i.v. insulin reverses hyperglycaemia-induced insulin resistance and substantially improves metabolic control. Subsequent CSII treatment, using insulin analogues, appears to maintain improved metabolic control for at least 1 year. This approach is promising but needs further evaluation.
AIMS: Despite high-dose s.c. insulin therapy, some Type 2 diabetes mellitus (DM) patients remain in poor metabolic control. We investigated whether a period of euglycaemia using i.v. insulin, followed by continuous subcutaneous insulin infusion (CSII), would ameliorate the deleterious effects of hyperglycaemia on insulin sensitivity and result in sustained, improved metabolic control. METHODS: In a prospective observational study, eight Type 2 DMpatients with severe insulin resistance (insulin dose 1.92 +/- 0.66 U/kg per day (mean +/-sd)), in poor metabolic control (HbA(1c) 12.0 +/- 1.7%), were treated with i.v. insulin for 31 +/- 10 days aimed at euglycaemia, followed by CSII therapy for 12 months, using insulin lispro. Before and after 28 +/- 6 days of i.v. insulin treatment, insulin sensitivity was measured by a hyperinsulinaemic euglycaemic clamp. RESULTS: Euglycaemia was reached after 12 +/- 6 days of i.v. insulin treatment. Subsequently, the i.v. insulin dose required to maintain euglycaemia decreased from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg per day (P < 0.005). Whole body glucose uptake increased from 12.7 +/- 5.7 to 22.4 +/- 8.8 micromol/kg per min (P < 0.0005). HbA(1c) decreased to 8.9 +/- 1.2% after 28 +/- 6 days, to 7.1 +/- 0.6% after 6 months and to 8.3 +/- 1.4% after 12 months (P < 0.001 vs. pretreatment, for all). Lipid profile improved and plasminogen activator inhibitor type 1 levels decreased significantly. Mean body weight did not change. CONCLUSIONS: In Type 2 diabeticpatients, who are poorly controlled despite high-dose s.c. insulin treatment, a period of 2 weeks of euglycaemia achieved by i.v. insulin reverses hyperglycaemia-induced insulin resistance and substantially improves metabolic control. Subsequent CSII treatment, using insulin analogues, appears to maintain improved metabolic control for at least 1 year. This approach is promising but needs further evaluation.