title: Autonomic and hemodynamic responses to insulin in lean and obese humans.
abstract: To study the acute effects of insulin on autonomic control of cardiac function, we performed spectral analysis of heart rate variability and measured cardiac dynamics (by two-dimensional echocardiography) in 18 obese (BMI = 35 +/- 1 kg.m-2) and 14 lean (BMI = 24 +/- 1 kg.m-2) subjects in the basal state and in response to physiological hyperinsulinemia (1 mU.min-1.kg-1 insulin clamp). In the lean group, insulin promptly (within 20 min) and consistently depressed spectral powers, both in the low-frequency and high-frequency range. These changes were twice as large as accounted for by the concomitant changes in heart rate (68 +/- 2 to 70 +/- 2 beats/min). At the end of the 2-h clamp, stroke volume (67 +/- 4 to 76 +/- 9 ml.min-1) and cardiac output (4.45 +/- 0.21 to 5.06 +/- 0.55 l.min-1) rose, whereas peripheral vascular resistance fell. The low-to-high frequency ratio increased from 1.7 +/- 0.2 to 2.3 +/- 0.3 (P < 0.01), indicating sympathetic shift of autonomic balance. In the obese group, all basal spectral powers were significantly lower (by 40% on average) than in the lean group, and were further reduced by insulin administration. The low-to-high frequency ratio was higher than in controls at baseline (2.4 +/- 0.4, P < 0.03), and failed to increase after insulin (2.2 +/- 0.3, P = ns). Furthermore, obesity was associated with higher resting stroke volume (89 +/- 5 vs. 67 +/- 4 ml.min-1, P < 0.01) and cardiac output (6.01 +/- 0.31 vs. 4.45 +/- 0.21 l.min-1, P = 0.001) but lower peripheral vascular resistance (15.1 +/- 0.8 vs. 19.2 +/- 1.1 mmHg.min.L-1, P = 0.002), whereas mean arterial blood pressure was similar to control (90 +/- 2 vs. 86 +/- 2 mmHg, P = not significant). We conclude that physiological hyperinsulinemia causes acute desensitization of sinus node activity to both sympathetic and para-sympathetic stimuli, sympathetic shift of autonomic balance, and a high-output, low-resistance hemodynamic state. In the obese, these changes are already present in the basal state, and may therefore be linked with chronic hyperinsulinemia.
authors.affiliation: Coronary Division, University of Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Muscelli
authors.forename: M
authors.initials: M
authors.lastname: Emdin
authors.forename: A
authors.initials: A
authors.lastname: Natali
authors.forename: L
authors.initials: L
authors.lastname: Pratali
authors.forename: S
authors.initials: S
authors.lastname: Camastra
authors.forename: A
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: S
authors.initials: S
authors.lastname: Baldi
authors.forename: C
authors.initials: C
authors.lastname: Carpeggiani
authors.forename: E
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D015992:Body Mass Index; D002302:Cardiac Output / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D007328:Insulin; D019382:Human Growth Hormone; D013972:Thyrotropin; D003346:Corticotropin-Releasing Hormone