Similar Metabolic Effects of Pulsatile Versus Continuous Human Insulin Delivery During Euglycemic, Hyperinsulinemic Glucose Clamp in Normal Man

Seven normal volunteers were studied on two different occasions during which 4-h pulsatile (PULS: 0.8 mU · kg⁻¹ · min⁻¹, 7.5 min of 15) and continuous (CONT: 0.4 mU · kg⁻¹ · min1) intravenous (i.v.) infusions of human insulin (Actrapid HM, Novo) were randomly compared. A euglycemic glucose clamp was performed and a 3-³H-glucose infusion was used for determination of endogenous glucose production (EGP) and metabolic clearance rate (MCR) of glucose. Plasma glucose was similar in both conditions; plasma insulin was stable at about 29 mU/L (CONT) and fluctuated between 10 and 45 mU/L (mean: 28, PULS). Exogenous glucose infused was 1.137 ± 0.058 and 1.088 ± 0.099 g · kg⁻¹ · 4h⁻¹ in CONT and PULS, respectively (NS). EGP was totally suppressed in both conditions. Glucose MCR increased similarly to a maximum of 6.71 ± 0.19 (CONT) and 6.79 ± 0.59 (PULS) ml · kg⁻¹ · min⁻¹ during the fourth hour. C-peptide plasma levels remained stable, whereas plasma glucagon, free fatty acids, and 3-hydroxybutyrate were similarly suppressed in both tests. Thus, under these conditions, pulsatile and continuous insulin infusions have similar metabolic effects. These data contrast with those of Matthews et al. (1983) who reported that, at lower plasma concentrations (5–19 mU/L), pulsatile insulin had greater hypoglycemic effect than did continuous delivery. It is concluded that pulsatile insulin shows no greater activity under normoglycemic, moderately hyperinsulinemic conditions in man.