Different Absorption of Isophane (NPH) Insulin from Subcutaneous and Intramuscular Sites Suggests a Need to Reassess Recommended Insulin Injection Technique

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Abstract
The absorption of isophane (NPH) insulin from subcutaneous and intramuscular injection sites was measured in seven healthy volunteers using the euglycaemic clamp technique. Human Insulatard (Nordisk, Gentofte, Denmark) was administered in a dose of 0.25 U kg-body-weight-1 into the anterior compartment of the thigh. In random order injections were given either subcutaneously, via 12 mm needle at 45 degrees to the skin into a skinfold, or intramuscularly by 25 mm needle perpendicularly to the skin. Insulin concentrations rose more rapidly after intramuscular injection than after subcutaneous injection, being significantly higher as early as 60 min after injection (19.7 +/- 1.6 (+/- SE) vs 8.7 +/- 1.4 mU l-1; p less than 0.001). Thereafter insulin concentrations remained significantly higher for the remaining 360 min of study, reflected by a significantly greater area under the insulin concentration curve for the 420 min study (IM 8630 +/- 1256 vs SC 4908 +/- 465 mU l-1 min, p less than 0.05). A significantly greater quantity of infused glucose was required to maintain euglycaemia after intramuscular injection than after subcutaneous injection (923 +/- 256 vs 216 +/- 71 mg kg-1 min, p less than 0.05). These results demonstrate a striking difference in the pharmacokinetics of an isophane (NPH) insulin when injected into subcutaneous fat and muscle.