Effect of raising injection-site skin temperature on isophane (NPH) insulin crystal dissociation

In eight healthy subjects, skin temperature at the injection site was raised from mean +/- SD 31.7 +/- 0.5 to 40.8 +/- 0.9 degrees C 180 min after injection of 0.25 U/kg isophane (NPH; Human Insulatard) insulin and maintained for 180 min. On the control day, skin temperature was kept constant. On warming of the injection site, serum insulin concentration rose from mean +/- SE 14.4 +/- 2.5 to 17.7 +/- 3.1 mU/L after 40 min (P less than .01) but did not change on the control day over the same period. The change in insulin concentration from the prewarming hour was higher on the warming day than control day in the 1st h (123 +/- 8 vs. 93 +/- 7%, P less than .01), 2nd h (115 +/- 14 vs. 83 +/- 9%, P less than .05), and 3rd h (113 +/- 17 vs. 80 +/- 10%, P less than .05) of warming, providing evidence for both early increased absorption of the free-insulin pool surrounding the protamine-insulin complexes and continuing increased dissociation of the complexes.