Pharmacodynamics of insulin Lispro in 2 patients with type II diabetes mellitus

We studied the effects of the new rapid acting human insulin analogue (Lys(B28), Pro(B29) insulin), insulin Lispro (Lispro) on metabolic control and insulin receptor binding in type II diabetes mellitus. We investigated 2 patients: Patient 1 was obese, clearly insulin-resistant, injected high doses of insulin (3-4 IU/kg body weight), and had insufficient diabetes control. Patient 2 was of normal body weight, injected normal insulin doses (0.7-0.8 IU/kg body weight), and had good diabetes control. Patient 1 showed a considerable improvement of insulin binding after receiving Lispro (26,700 vs. 5,600 receptors/monocyte; Kd 560 vs. 1,500 pM). Concommitantly, a decrease of serum glucose and insulin dose was observed, reflecting a higher insulin sensitivity during Lispro treatment. In patient 2 injected with Lispro the time course of serum glucose, serum insulin, and insulin binding after an oral meal was comparable to values obtained in healthy controls. We conclude that the quick and pulsatile pharmacokinetic profile of the insulin analogue Lispro may improve glycemia, insulin receptor binding, and insulin resistance in type II diabetes.