Effects of different insulin infusion rates on heart rate variability in lean and obese subjects.
The low-frequency to high-frequency ratio (LF/HF ratio) is an index of cardiac sympathovagal balance. We hypothesized that insulin might also stimulate the LF/HF ratio. Thus, 15 lean and 15 obese subjects were studied. Each subject underwent sequential hyperinsulinemic clamps (insulin infusion rate 0.50, 1, and 2 mU/kg x min) while the heart rate was recorded by the Holter technique continuously. Indirect calorimetry allowed determination of the respiratory quotient (Rq) and substrate oxidation. The leg blood flow (LBF), leg vascular resistance (LVR), and plasma norepinephrine concentration were also measured. In seven lean subjects, hyperinsulinemic clamps were repeated along with propranolol infusion (0.1 mg x kg(-1) as an intravenous bolus dose followed by continuous intravenous infusion of 0.5 mg x kg(-1) x min(-1) throughout the study). Lean subjects had better insulin action than obese subjects. Insulin infusion was associated with an increase of the deltaLF/HF ratio in both lean (P < .001 for time-dependent changes) and obese (P < .02 for time-dependent changes) subjects; however, the extent of insulin-mediated stimulation of the LF/HF ratio was greater in lean versus obese subjects. Insulin infusion did not significantly affect HF values in both groups. Independently of gender, body fat, changes in the plasma norepinephrine concentration, LBF, and LVR, the deltaLF/HF ratio at the end of the fastest insulin infusion (0.8 +/- 0.2 v 0.3 +/- 0.2, P < .04) was still greater in lean versus obese subjects. The deltaLF/HF ratio was also more stimulated during insulin versus insulin + propranolol infusion in lean subjects. In conclusion, insulin stimulates the LF/HF ratio in both lean and obese subjects and thus produces a shift in the cardiac autonomic nervous system activity toward sympathetic predominance.
Paolisso
G
G
Department of Geriatric Medicine and Metabolic Diseases, II University of Naples, Italy.
Manzella
D
D
Tagliamonte
M R
MR
Rizzo
M R
MR
Gambardella
A
A
Varricchio
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D002153:Calorimetry, Indirect; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory; D005260:Female; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011433:Propranolol; D009638:Norepinephrine