The effects of HDV-insulin on carbohydrate metabolism in Type 1 diabetic patients

The aim of this study was to compare the metabolic effects of a single equi molar subcutaneous injection of hepatic directed vesicle-insulin (HDV-insul in) and regular insulin on glucose levels and intermediary metabolism durin g a 75-g oral glucose tolerance test (OGTT). Nine Type I diabetic patients underwent two experiments separated by 4 weeks. Each experimental protocol consisted of an identical evening meal followed by overnight euglycemic con trol achieved by a continuous low-dose insulin infusion. The next morning a subcutaneous injection (0.1 U/kg) of HDV-insulin or regular insulin was ad ministered 30 min before a 75-g OGTT. The overnight basal insulin infusion was maintained unaltered throughout the 150-min OGTT. Plasma glucose, gluco regulatory hormones (insulin, glucagon, cortisol), and intermediary metabol ites (lactate, alanine, glycerol, NEFA, beta -hydroxybutyrate) were measure d to assess the metabolic effects of the two insulin preparations. Compared to regular insulin, an equivalent subcutaneous dose of HDV-insulin signifi cantly lowered glucose levels during OGTT (mean reduction 2.2 +/-0.4 mmol/l ; P<.005). Plasma levels of insulin and glucagon were equivalent during bot h series of experiments. Blood lactate, glycerol and plasma NEFA levels wer e not different during OGTT indicating similar peripheral action of the ins ulins. <beta>-Hydroxybutyrate levels were significantly reduced (P<.05) fol lowing HDV-insulin supporting a preferential hepatic action of the preparat ion. We conclude that HDV-insulin can significantly lower plasma glucose ex cursions compared to an equivalent dose of regular insulin during an OGTT i n Type 1 diabetic patients. The metabolic profile of equivalent peripheral insulin, glucagon and glycerol levels but reduced <beta>-hydroxybutyrate va lues support a hepatospecific effect of HDV-insulin. (C) 2001 Elsevier Scie nce Inc. All rights reserved.