Mechanisms of arterial hypotension after therapeutic dose of subcutaneous insulin in diabetic autonomic neuropathy

• Published in: Diabetes (New York, N.Y.) Vol. 42; no. 7; pp. 1055 - 1064
• Main Authors: Porcellati, F, Fanelli, C, Bottini, P, Epifano, L, Rambotti, A M, Lalli, C, Pampanelli, S, Scionti, L, Santeusanio, F, Brunetti, P
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.07.1993
• Subjects: Adult; Analysis of Variance; Blood Glucose - metabolism; Blood Pressure - drug effects; Development and progression; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diabetic neuropathies; Diabetic Neuropathies - blood; Diabetic Neuropathies - physiopathology; Female; Forearm - blood supply; Health aspects; Heart Rate - drug effects; Humans; Hypotension; Hypotension - chemically induced; Injections, Subcutaneous; Insulin; Insulin - administration & dosage; Insulin - blood; Insulin - therapeutic use; Male; Middle Aged; Norepinephrine - blood; Plasma Volume - drug effects; Posture; Regional Blood Flow - drug effects; Supine Position; Vascular Resistance - drug effects
• DOI: 10.2337/diab.42.7.1055
• ISSN: 0012-1797

To assess whether a therapeutic, subcutaneous injection of insulin exerts hemodynamic effects in subjects with IDDM, 0.2 U/kg regular insulin was injected subcutaneously in 17 IDDM subjects: 6 without autonomic neuropathy, 7 with autonomic neuropathy and othostatic hypotension, and 4 with autonomic neuropathy but without orthostatic hypotension. Plasma glucose was maintained at approximately 8.5 mM throughout the studies. Mean blood pressure, plasma norepinephrine concentration, forearm vascular resistances, and calf venous volume were measured before and 120 min after subcutaneous insulin, in the supine position and 5 min after standing. Supine plasma volume ([125I]albumin and [131I]albumin) was measured before and after subcutaneous injection of insulin. In all three groups, subcutaneous insulin activated the sympathetic nervous system (approximately 30% increase in norepinephrine concentration). In subjects with IDDM but without autonomic neuropathy, standing forearm vascular resistance increased approximately 70% less after subcutaneous insulin, but supine or standing mean blood pressure did not decrease. In contrast, in subjects with IDDM with autonomic neuropathy and orthostatic hypotension, subcutaneous insulin decreased supine mean blood pressure (from 99 +/- 3 to 94 +/- 5 mmHg) and exaggerated the standing decrement in mean blood pressure (24 +/- 3 vs. 19 +/- 2 mmHg) (P < 0.05). This was associated with a decrease in forearm vascular resistance. Similarly, in subjects with IDDM with autonomic neuropathy without orthostatic hypotension, subcutaneously injected insulin decreased supine mean blood pressure (from 95 +/- 2 to 89 +/- 2 mmHg) and standing mean blood pressure by 8 +/- 1 mmHg (P < 0.05). Calf venous volume was not affected by subcutaneous insulin in any of the three groups. Plasma volume did not change after subcutaneous insulin in subjects with IDDM without autonomic neuropathy, whereas it decreased in those with autonomic neuropathy and orthostatic hypotension from 1.692 +/- 0.069 to 1.610 +/- 0.064 L/m2, without orthostatic hypotension from 1.631 +/- 0.027 to 1.593 +/- 0.024 L/m2, P < 0.05). No hemodynamic effects were observed when subjects with IDDM were restudied in a control experiment where placebo (distilled water), not insulin, was injected subcutaneously. In conclusion, therapeutic doses of subcutaneous insulin activate the sympathetic nervous system; decrease blood pressure in subjects with IDDM with autonomic neuropathy, but not in those without, primarily by decreasing arterial vascular resistances and plasma volume; and have no effects of capacitance vessels. Thus, in subjects with IDDM without autonomic neuropathy, greater activation of sympathetic nervous system after subcutaneous injection of insulin prevents orthostatic hypotension.