Glucose-Lowering Effect of Insulin by Different Routes in Obese and Lean Nonketotic Diabetic Patients*

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Abstract
The absorption of insulin and its glucose-lowering effect were compared after the administration of crystalline insulin by sc, im, and iv routes in 20 obese and 10 lean nonketotic diabetic patients, none of whom had consciously received insulin previously. Each of the patients received insulin in a dose of 0.1 U/kg BW by the im, sc, and iv routes in a randomized fashion on 3 different days. Plasma glucose, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG) were measured at intervals over the first 4 h. The t1/2 (mean ± SEM) after iv administration of insulin in obese and lean diabetics was, respectively, 5.3 ± 0.2 and 4.8 ± 0.4 min; these were not significantly different. Intravenous injection produced its highest level of IRI in 2 min in both groups. Thereafter, a rapid drop was observed with return to the basal level by 90 min. Equivalent amounts of im and sc insulin produced a maximal increase in plasma IRI at 60 min in both groups. Plasma IRI after iv insulin injection was significantly higher than after sc and im insulin injections at 10 and 20 min (P < 0.001) and significantly lower than the im and sc groups at 60, 90, 120, 150, 180, 210, and 240 min (P < 0.001). After iv insulin, plasma glucose at 30, 40, 50, and 60 min was significantly lower than after im and sc insulin (P < 0.001), but over the 4-h study period, the glucoselowering effect and the area under the curves for glucose response to IRI by the three routes were the same in both lean and obese diabetic subjects. The mean basal IRI in lean patients was 18 ± 4 μU/ml, which was significantly lower (P < 0.05) than in obese patients (26 ± 2 μU/ml). No significant difference was observed in fasting IRG in lean (96 ± 12 pg/ml) vs. obese (108 ± 10 pg/ml) patients. No significant increase in IRG was noted with equivalent amounts of sc, im, and iv injection in the lean and obese patients. These studies demonstrate that although iv injection of insulin produces a more rapid initial decline in plasma glucose, the overall glucose-lowering effect by insulin given iv, im, or sc is similar in nonketotic lean or obese diabetic subjects.