Submitted on April 22, 2002
Accepted on January 13, 2003
Responsiveness of insulin-induced cardiac sympathetic nerve activation associates with blood pressure regulation in diabetics
Miki Takagi1, Yasushi Tanaka1*, Yoshimitsu Yamasaki2, Masahiko Yamamoto2, Masatsugu Hori2, Tomiko Nakaniwa1, Masataka Niwa1, Hiroshi Uchino1, Yoshifumi Tamura1, Takashi Nomiyama1, Hirotaka Watada1, and Ryuzo Kawamori1
1 Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan
2 The First Department of Medicine, Osaka University, Osaka, Japan
* To whom correspondence should be addressed. E-mail: y-tanaka{at}med.juntendo.ac.jp.
The effect of an acute insulin load on cardiac sympathetic nerve activity (SNA) and the clinical factors associated with insulin sensitivity for the regulation of SNA were investigated in type 2 diabetic subjects without neuropathy. A total of 29 Japanese type 2 diabetics without symptoms or signs of peripheral and autonomic neuropathy were recruited. A 2-h control study (9:00-11:00 AM) while resting on a bed and a 2-h hyperinsulinemic euglycemic glucose clamp study (9:00-11:00 AM) on the day after the control study were each performed after an overnight fast. Power spectral analysis of R-R intervals was done using Holter electrocardiogram (ECG) records obtained during both studies, and two major frequency components were calculated: the low frequency component (LF, 0.03-0.15 Hz) and the high frequency component (HF, 0.15-0.4 Hz). Then the percent LF (%LF) was calculated from LF/(LF+HF) as an indicator of cardiac SNA. The ratio of the average %LF during the last 30 min of the clamp or control study to the average %LF for the entire clamp or control study (R-%LF) was used as a marker of the change in SNA. R-%LF was significantly higher during the clamp study than during the control study (1.07 ± 0.04 vs. 1.03 ± 0.03, p < 0.05). The high responders (R-%LF during the clamp study 
mean + 2SD for the control study) showed a significantly higher basal mean BP before the clamp study, but not a significantly higher glucose infusion rate (GIR) compared with the low responders (R-%LF during clamp < mean + 2SD for the control study). Furthermore, multiple regression analysis showed a positive correlation of R-%LF with basal mean BP (p < 0.02), but not with GIR. These findings demonstrate that an acute insulin load stimulates cardiac SNA (as evaluated by power spectral analysis of the R-R interval) and that the responsiveness of SNA to insulin may be associated with BP regulation independently of peripheral insulin sensitivity.
