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 con trol and insulin receptor binding in type II diabetes mellitus, We inv estigated 2 patients: Patient 1 was obese, dearly insulin-resistant, i njected high doses of insulin (3 - 4 IU/kg body weight), and had insuf ficient diabetes control. Patient 2 was of normal body weight, injecte d normal insulin doses (0.7 - 0.8 IU/kg body weight), and had good dia betes control. Patient 1 showed a considerable improvement of insulin binding after receiving Lispro (26,700 vs, 5,600 receptors/monocyte; K -d 560 vs. 1,500 pM). Concommitantly, a decrease of serum glucose and insulin dose was observed, reflecting a higher insulin sensitivity dur ing Lispro treatment. In patient 2 injected with Lispro the time cours e of serum glucose, serum insulin, and insulin binding after an oral m eal was comparable to values obtained in healthy controls, We conclude that the quick and pulsatile pharmacokinetic profile of the insulin a nalogue Lispro may improve glycemia, insulin receptor binding, and ins ulin resistance in type II diabetes.