Intravenous Insulin Causing Loss of Intravascular Water and Albumin and Increased Adrenergic Nervous Activity in Diabetics

Abstract

Blood pressure, heart rate, plasma norepinephrine, forearm blood flow, plasma volume, plasma albumin, blood glucose, and plasma epinephrine were measured in six diabetic patients without neuropathy in the supine position and during feet-down tilting for seven minutes. The experiments were repeated after intravenous (i.v.) injection of 6 to 8 U. of insulin. The mean blood glucose concentration averaged 205 ± 14 (S. E. M.) mg./100 ml. in the control experiment and had decreased by 97 ± 17 mg./100 ml. 45 minutes after the injection of insulin. None of the patients had hypoglycemia, and plasma epinephrine did not increase. There was no change in arterial blood pressure after insulin was given either in the supine position or after tilting. The heart rate averaged 64 ± 5 beats per minute in the control experiment and had increased by 7 ± 2 beats per minute 40 minutes after the injection of insulin (2p = 0.035). The rise in heart rate In response to tilting was statistically significantly greater after administration of insulin (2p = 0.0064). Plasma norepinephrine averaged 0.17 ± 0.03 ng./ml. in the control experiment and had increased by 70 ± 24 per cent 45 minutes after the i.v. injection of insulin (2p = 0.045). The rise in plasma norepinephrine in response to tilting was statistically significantly greater after the injection of insulin (2p = 0.017). Forearm blood flow decreased from 2.13 ± 0.29 ml./l00 ml. per minute in the control experiment to 1.63 ± 0.32 ml./100 ml. per minute 40 minutes after the injection of insulin (2p = 0.011). Plasma volume averaged 3,061 ± 67 ml. before injection of insulin and had decreased by 265 ± 59 ml. 45 minutes after insulin was given (2p = 0.011). The intravascular mass of albumin averaged 118 ± 3 gm. and 109 ± 3 gm. before and 45 minutes after the administration of insulin, respectively (2p = 0.017). There was a dose correlation between the relative increase in plasma norepinephrine in the supine position and the relative decrease in plasma volume after the injection of insulin (r = −0.95, 2p = 0.013). It is concluded that i.v. injection of insulin results in an increased adrenergic nervous activity that is due to a decrease in plasma volume. The effect of insulin is accompanied by a significant reduction in the intravascular pool of albumin. These observations may explain the fact that patients with abnormal cardiovascular reflexes are unable to maintain arterial blood pressure, especially in the upright position, after the i. v. injection of insulin. The observed decrease in plasma volume after the administration of insulin was much larger than could be expected from the decrease in blood glucose concentration and the ensuing decrease in plasma osmolality. It is suggested that insulin either directly or secondarily to its metabolic effects may alter the function or the volume of the endothelial cells and thereby increase the transfer of fluid and albumin out of the vascular system.