Comparison of insulin aspart and lispro: pharmacokinetic and metabolic effects.

OBJECTIVE To compare insulin levels and actions in patients with type 1 diabetes after subcutaneous injection of the rapid-acting insulin analogs aspart and lispro. RESEARCH DESIGN AND METHODS Seven C-peptide-negative patients with type 1 diabetes (two men and five women) were studied at the General Clinical Research Center at Temple University Hospital two times, 1 month apart. Their plasma glucose was normalized overnight by intravenous infusion of insulin. The next morning, they received subcutaneous injections of either aspart or lispro (9.4 +/- 1.9 U) in random order. For the next 4-5 h, their plasma glucose was clamped at approximately 5.5 mmol/l with a variable infusion of 20% glucose. The study was terminated after 8 h. RESULTS Both insulin analogs produced similar serum insulin levels (250-300 pmol/l) at approximately 30 min and disappeared from serum after approximately 4 h. Insulin aspart and lispro had similar effects on glucose and fat metabolism. Effects on carbohydrate metabolism (glucose uptake, glucose oxidation, and endogenous glucose production) peaked after approximately 2-3 h and disappeared after approximately 5-6 h. Effects on lipid metabolism (plasma free fatty acid, ketone body levels, and free fatty acid oxidation) appeared to peak earlier (at approximately 2 h) and disappeared earlier (after approximately 4 h) than the effects on carbohydrate metabolism. CONCLUSIONS We conclude that both insulin aspart and lispro are indistinguishable from each other with respect to blood levels and that they are equally effective in correcting abnormalities in carbohydrate and fat metabolism in patients with type 1 diabetes.

[1]  Gernot Brunner,et al.  A direct comparison of insulin aspart and insulin lispro in patients with type 1 diabetes. , 2002, Diabetes care.

[2]  P. Home,et al.  Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group. , 1998, Diabetes care.

[3]  P. Brunetti,et al.  Effects of the Short-Acting Insulin Analog [Lys(B28),Pro(B29)] on Postprandial Blood Glucose Control in IDDM , 1996, Diabetes Care.

[4]  R. Steele,et al.  Measurement of size and turnover rate of body glucose pool by the isotope dilution method. , 1956, The American journal of physiology.

[5]  H. Arnqvist,et al.  Direct comparison of insulin lispro and aspart shows small differences in plasma insulin profiles after subcutaneous injection in type 1 diabetes. , 2001, Diabetes care.

[6]  L. Vignati,et al.  Reduction of Postprandial Hyperglycemia and Frequency of Hypoglycemia in IDDM Patients on Insulin-Analog Treatment , 1997, Diabetes.

[7]  M. Feinglos,et al.  Modification of Postprandial Hyperglycemia With Insulin Lispro Improves Glucose Control in Patients With Type 2 Diabetes , 1997, Diabetes Care.

[8]  P. Home,et al.  Comparative pharmacokinetics and pharmacodynamics of the novel rapid-acting insulin analogue, insulin aspart, in healthy volunteers , 1999, European Journal of Clinical Pharmacology.

[9]  M. Stumvoll,et al.  Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine. , 1995, The Journal of clinical investigation.

[10]  G. Boden,et al.  Glucose metabolism and leg blood flow after pancreas/kidney transplantation. , 1993, Journal of Clinical Endocrinology and Metabolism.

[11]  R. Heine,et al.  Metabolic Efficacy of Preprandial Administration of Lys(B28), Pro(B29) Human Insulin Analog in IDDM Patients: A comparison with human regular insulin during a three-meal test period , 1997, Diabetes Care.

[12]  K. Birkeland,et al.  Improved postprandial glycaemic controls with insulin Aspart in type 2 diabetic patients treated with insulin , 2000, Acta Diabetologica.

[13]  L. Groop,et al.  Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans. , 1990, The American journal of physiology.

[14]  Lawrence A Leiter,et al.  Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes. , 2000, Diabetes care.

[15]  O. Owen,et al.  Effects of Therapy on the Nature and Quantity of Fuels Oxidized During Diabetic Ketoacidosis , 1980, Diabetes.

[16]  L. Vignati,et al.  Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group. , 1997 .

[17]  A. Lindholm,et al.  Insulin aspart vs. human insulin in the management of long‐term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial , 2000, Diabetic medicine : a journal of the British Diabetic Association.

[18]  R. DeFronzo,et al.  Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. , 1985, The Journal of clinical investigation.

[19]  R. Wolfe,et al.  Tracers in metabolic research: radioisotope and stable isotope/mass spectrometry methods. , 1985, Laboratory and research methods in biology and medicine.

[20]  L. Tappy,et al.  Effect of Hyperinsulinemia on Urea Pool Size and Substrate Oxidation Rates , 1988, Diabetes.

[21]  M. Marre,et al.  Improved glycemic control with insulin aspart in type-1 diabetic patients using algorith-driven dose optimization , 2000 .

[22]  H C Lukaski,et al.  Methods for the assessment of human body composition: traditional and new. , 1987, The American journal of clinical nutrition.