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The Journal of Clinical Endocrinology & Metabolism 92(10):3885–3889
Copyright © 2007 by The Endocrine Society
doi: 10.1210/jc.2006-2175
Epidemiological Evidence of Altered Cardiac Autonomic
Function in Subjects with Impaired Glucose Tolerance
But Not Isolated Impaired Fasting Glucose
Jin-Shang Wu, Yi-Ching Yang, Thy-Sheng Lin, Ying-Hsiang Huang, Jia-Jin Chen, Feng-Hwa Lu,
Chih-Hsing Wu, and Chih-Jen Chang
Departments of Family Medicine (J.-S.W., Y.-C.Y., F.-H.L., C.-J.C.) and Neurology (T.-S.L.), College of Medicine; and
Institute of Biomedical Engineering (J.-J.C.), Department of Family Medicine, National Cheng Kung University Hospital
(J.-S.W., Y.-C.Y., Y.-H.H., F.-H.L., C.-H.W., C.-J.C.), National Cheng Kung University, 70441 Taiwan, Republic of China
Context: Autonomic dysfunction is present in diabetes mellitus
(DM), but no study is available on alteration in cardiac autonomic
function (CAF) across different glycemic statuses including normal
glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM.
Objective: Our objective was to examine whether CAF is altered in
subjects with IGT and isolated IFG.
Design and Setting: The study was a stratified systematic cluster
sampling design within the general community.
Participants: A total of 1440 subjects were classified as NGT (n ⫽
983), isolated IFG (n ⫽ 163), IGT (n ⫽ 188), and DM (n ⫽ 106).
Main Outcome Measure: CAF was determined by 1) standard deviation of normal-to-normal (SDNN) or RR interval, power spectrum
in low and high frequency (LF, 0.04 – 0.15 Hz; HF, 0.15– 0.40 Hz), and
D
IABETES MELLITUS (DM) is one of the most common
causes of autonomic neuropathy, which affects cardiovascular, gastrointestinal, urogenital, thermoregulatory,
sudomotor, and pupillomotor functions (1, 2). Dysfunction
of cardiovascular autonomic activity, reflected by reduced
heart rate variability (HRV), is strongly associated with the
increased risk of cardiac events (3–5) and overall mortality (3,
6). Diabetic autonomic neuropathy with reduced HRV, even
when subclinical, increases the risk of mortality (1, 7, 8).
Traditional tests for cardiac autonomic function (CAF),
such as a change in heart rate during deep breathing (HRDB)
and the ratio between 30th and 15th RR interval after standing from supine position (30/15 ratio) have been performed
in the past. Both HRDB and 30/15 ratio are the indices of
First Published Online July 31, 2007
Abbreviations: ADA, American Diabetes Association; ARIC, Atherosclerosis Risk in Communities; BMI, body mass index; CAF, cardiac
autonomic function; DM, diabetes mellitus; ECG, electrocardiography;
FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol; HF, high frequency; HRDB, heart rate during deep breathing; HRV,
heart rate variability; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; LF, low frequency; NGT, normal glucose tolerance; PG,
post-load glucose; SDNN, standard deviation of normal-to-normal.
JCEM is published monthly by The Endocrine Society (http://www.
endo-society.org), the foremost professional society serving the endocrine community.
LF/HF ratio in supine position for 5 min; 2) ratio between 30th and
15th RR interval after standing from supine position (30/15 ratio); and
3) average heart rate change during breathing of six deep breaths for
1 min (HRDB).
Results: Univariate analysis showed significant differences in
SDNN, 30/15 ratio, HRDB, HF power, and LF/HF ratio among subjects
with NGT, isolated IFG, IGT, and DM. In multivariate analysis, none
of the indices of CAF was related to isolated IFG in the reference group
of NGT. IGT and DM were negatively associated with 30/15 ratio and
HF power but positively associated with LF/HF ratio. In addition, DM
was also related to a lower SDNN.
Conclusions: DM and IGT subjects had an impaired CAF independent of other cardiovascular risk factors. The risk of altered CAF is
not apparent in subjects with isolated IFG. (J Clin Endocrinol
Metab 92: 3885–3889, 2007)
parasympathetic modulation of the heart. Time and frequency domain methods for HRV assessment have been
applied during the last decade (9). The standard deviation of
normal-to-normal (SDNN) intervals or RR intervals reflects the cardiac vagal activity in the time domain (9). The
frequency components of HRV, derived from power spectral analysis, reflects the cardiac sympathovagal balance
(9, 10). The parasympathetic activity is the major contributor to the high-frequency (HF, 0.15– 0.40 Hz) component
(11), and the low-frequency (LF, 0.04 – 0.15 Hz) component
is suggested as a major quantitative marker of sympathetic
modulations (11, 12). The LF/HF ratio is the index of
sympathovagal balance (9).
Abnormal HRV has been identified in persons with DM (8,
11–13). The Hoorn Study showed a reduced SDNN in subjects with impaired glucose tolerance (IGT), but they didn’t
report the effect of impaired fasting glucose (IFG) on HRV
(14). In the Framingham Heart Study, a fasting plasma glucose (FPG) of 6.1– 6.9 mmol/liter was used to define IFG, and
subjects with IFG had decreased SDNN and LF and HF
power compared with normal control subjects (3). The Atherosclerosis Risk in Communities (ARIC) study adopted the
American Diabetes Association (ADA) 2004 criteria (15), and
their IFG subjects with a FPG of 5.6 – 6.9 mmol/liter had a
lower RR interval, but not a lower SDNN, than subjects with
a normal FPG (16). Because some of the IFG subjects may
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J Clin Endocrinol Metab, October 2007, 92(10):3885–3889
have IGT and even DM (17, 18), both the Framingham Heart
Study and the ARIC study didn’t exclude the influence of
IGT and DM on IFG subjects (3, 16). There is a paucity of
studies that assess the CAF in IGT and IFG subjects (3, 14, 16),
and no study is available on HRV change across the different
blood glucose levels, including normal glucose tolerance
(NGT), isolated IFG, IGT, and DM. Therefore, the aim of this
study is to examine whether CAF is altered in community
dwellers with IGT and isolated IFG from population-based
data in Tainan, Taiwan.
Subjects and Methods
Wu et al. • Cardiac Autonomic Function in IGT and IFG
lying to the standing position, and then 3) six deep breaths over 1 min
while sitting after a 10-min rest. The signal-acquiring and processing
system converted the analog signals to digital signals at a sampling rate
of 120 Hz per channel with a 12-bit performance by the data acquisition
devices for universal serial bus (DAQPad-6020E and SCB-68; National
Instruments, Taipei City, Taiwan). The ECG signals were processed to
extract the R-peak positions. The procedure for R-peak detection was
performed using software with a LabView 6.1 program (National Instruments). A power spectral analysis was used to define the temporal
fluctuations of HRV. The total power, very-low-frequency (⬍0.04 Hz),
LF (0.04 – 0.15 Hz), and HF (0.15– 0.4 Hz) components were identified for
each subject (9). The CAF included the following: 1) SDNN, LF power,
HF power, and LF/HF ratio in the supine position for 5 min; 2) 30/15
ratio; and 3) the average of six HRDB for 1 min while sitting after a 10-min
rest.
Study population
The subjects were recruited for the population-based study for
chronic diseases conducted in Tainan, and the details of its results have
been described elsewhere (19). A three-stage sampling scheme was used
to generate a stratified systemic cluster sample of households throughout the city. First, the city was classified into seven strata according to
its administrative districts. In each of the districts, one area was randomly selected from each stratum by adopting a probability proportional to the size of the areas within that specific stratum. Second, every
fifth household within each of the seven selected areas was systematically identified. Third, the members of each household aged at least 20
yr old were invited to participate in the study, and a total of 2416 eligible
subjects were selected. A total of 1638 subjects, representing a response
rate of 67.8%, finished a health screening examination. The nonresponders were slightly younger and consisted of more men as compared
with the responders, but the differences were not statistically significant.
Written consent was obtained from all participants, and this study was
approved by the research committee of National Cheng Kung University
Hospital, Taiwan. In the final analysis, a total of 1440 participants were
included after excluding 198 subjects who had taken medications known
to influence CAF, such as antihypertensive drugs, antiparkinsonism
drugs, narcotics, sedatives, antipsychotics, or antidepressants within 2
wk of the study.
Clinical examination
All the subjects were informed of unrestricted diet and usual physical
activity at least 3 d before the schedule of examinations by letter and
telephone. The subjects were instructed not to consume alcohol, coffee,
tea, or cigarettes on the day of the examination. They were interviewed
by a well-trained assistant, using a structured questionnaire, which
included questions on demographic characteristics, medical history, and
use of medications, dietary habits, cigarette smoking, alcohol drinking,
and physical activity during the past year. All the subjects received a
physical examination by physicians. Measurements of blood pressure
when seated, body weight, and height were taken by well-trained
nurses. The laboratory tests included blood biochemistry, urine examination, and electrocardiography (ECG) after an overnight fast of at least
10 h. The subjects without a history of DM received a 75-g oral glucose
tolerance test after completion of the measurement of their blood pressure and HRV. A blood sample was obtained 2 h after the subject began
to drink the glucose solution.
Measurements of blood pressure and HRV
All the subjects were informed of the purpose and procedures of the
test. Subjects were resting in a supine position in a quiet ambience, and
measurements were obtained in a fasting state between 0800 and 1000 h.
Two seated blood pressure readings, separated by intervals of at least
5 min, were taken with an appropriate-sized cuff wrapped around the
right upper arm by a DINAMAP vital sign monitor (model 1846SX;
Critikon Inc., Irvine, CA) after the subject had rested for 15 min.
The beat-to-beat duration of the cardiac cycle (RR interval) was measured continuously with an ECG monitor (CardiSuny ␣-800; Fukuda
M-E Kogyo Inc., Tokyo, Japan) on a personal computer-based dataacquisition system according to the following sequence: 1) normal
breathing for 5 min in the supine position, 2) an active change from the
Definition of clinical measurements
NGT was defined as an FPG of less than 5.6 mmol/liter, a 2-h postload glucose (PG) of less than 7.8 mmol/liter, and no previous history
of DM (15). Isolated IFG was identified as an FPG of 5.6 – 6.9 mmol/liter
and a 2-h PG of less than 7.8 mmol/liter without a DM history. IGT was
defined as a 2-h PG of 7.8 –11.1 mmol/liter and an FPG of less than 7.0
mmol/liter without a DM history. Subjects with both IFG and IGT were
classified as IGT. DM was diagnosed when subjects registered an FPG
of at least 7.0 mmol/liter or a 2-h PG of at least 11.1 mmol/liter or
reported having a DM history or current use of insulin or an oral
hypoglycemic agent (15). Hypertension was defined as the average of
two seated systolic/diastolic blood pressure measurements of at least
140/90 mm Hg or a positive history of hypertension (20). Total physical
activity, including work, walking, and leisure-time exercise, was measured in metabolic equivalent-hours per week for the past year (21).
Statistical analysis
Data analyses were performed using the Statistical Package for Social
Sciences 13.0 for Windows software. Glycemic status was divided into
NGT, isolated IFG, IGT, and DM groups. In the univariate analysis, the
ANOVA and Bonferroni post hoc test were used to compare continuous
variables among the subjects with different glycemic statuses, except
that Kruskal-Wallis test was used for comparison of the plasma triglyceride and physical activity level. A square root transformation of LF/HF
ratio was used to make the values follow a normal distribution due
to its nonnormal distribution. Comparisons of categorical variables
were made using the ␹2 or Fisher’s exact test, when the cell size was
less than 5.
Multiple linear regression was used to model the links between HRV
and different glycemic statuses. Three dummy variables were used to
code NGT (0, 0, 0), isolated IFG (1, 0, 0), IGT (0, 1, 0), and DM (0, 0, 1).
The outcome variables were HRV including SDNN, 30/15 ratio, HRDB,
LF power, HF power, and the square root of LF/HF ratio, respectively.
The predictor variables included age, gender, body mass index (BMI),
plasma cholesterol, triglyceride and high-density lipoprotein cholesterol
(HDL-C), hypertension, isolated IFG vs. NGT, IGT vs. NGT, DM vs. NGT,
and the physical activity levels. To make survey estimates a better
representation of population estimates, design weights, which were
calculated as the inverse of the sample selection probability, were used
in the regression model. A P value of ⬍ 0.05 was considered significant.
Results
The subjects were classified as NGT (n ⫽ 983), isolated IFG
(n ⫽ 163), IGT (n ⫽ 188), and DM (n ⫽ 106) according to ADA
2004 criteria (Table 1). Of 106 diabetic subjects, 56 were newly
diagnosed with diabetes or no antidiabetic medication, 44
took oral antidiabetic drug, including sulfonylurea and metformin, and six used insulin. Table 2 shows the comparisons
of clinical variables among subjects with NGT, isolated IFG,
IGT, and DM. There were significant differences in age, BMI,
physical activity levels, the average of two seated heart rate
measurements, systolic/diastolic blood pressure measure-
Wu et al. • Cardiac Autonomic Function in IGT and IFG
J Clin Endocrinol Metab, October 2007, 92(10):3885–3889
3887
TABLE 1. Subjects classified as NGT, IFG, IGT, and DM by FPG and 2-h PG according to ADA criteria
2-h PG
FPG
⬍5.6 mmol/liter
5.6 – 6.9 mmol/liter
ⱖ7.0 mmol/liter or DM history (⫹)
Total
A total of 1440 subjects were classified as follows:
a
⬍7.8
mmol/liter
7.8 –11.1
mmol/liter
ⱖ11.1 mmol/liter
or DM history (⫹)
Total
983a
163b
1d
1147
122c
66c
1d
189
11d
25d
68d
104
1116
254
70
1440
NGT (n ⫽ 983);
ments, FPG, glycosylated hemoglobin (HbA1c), plasma cholesterol, triglyceride, and HDL-C, and the prevalence of hypertension among these four groups (P ⬍ 0.001). However,
the differences based on gender (P ⫽ 0.327) and the prevalence of current smoking (P ⫽ 0.501) and alcohol use (P ⫽
0.691) were not significant.
Table 3 shows the comparisons of CAF among subjects
with NGT, isolated IFG, IGT, and DM. There were significant
differences in SDNN (P ⬍ 0.001), 30/15 ratio (P ⬍ 0.001),
HRDB (P ⬍ 0.001), HF power (P ⬍ 0.001), and the square root
of LF/HF ratios (P ⬍ 0.001) but not the LF power (P ⫽ 0.553)
among these four groups. The following results were analyzed by post hoc test. Compared with NTG subjects, subjects
with isolated IFG had a significantly lower SDNN (P ⫽ 0.005)
and HRDB (P ⬍ 0.001). Subjects with IGT and DM had a lower
SDNN (IGT, P ⬍ 0.001; DM, P ⬍ 0.001), 30/15 ratio (IGT, P ⬍
0.001; DM, P ⬍ 0.001), HRDB (IGT, P ⬍ 0.001; DM, P ⬍ 0.001),
and HF power (IGT, P ⬍ 0.001; DM, P ⬍ 0.001), but they had
a higher square root of LF/HF ratio (IGT, P ⬍ 0.001; DM, P ⬍
0.001) than NTG subjects. Compared with subjects with isolated IFG, both IGT and DM subjects had a higher square root
of LF/HF ratio (IGT, P ⬍ 0.001; DM, P ⬍ 0.001). Furthermore,
DM subjects suffered from a lower SDNN (P ⫽ 0.006), HRDB
(P ⫽ 0.001), and HF power (P ⫽ 0.003) than subjects with
isolated IFG and also had a significant lower HRDB than IGT
subjects (P ⫽ 0.001). However, there were not apparently
differences in the other CAF indices between IGT and DM
subjects.
For the multivariate analysis, Fig. 1 showed SDNN was
inversely associated with DM (P ⫽ 0.041) but not IFG (P ⫽
b
IFG (n ⫽ 163); c IGT (n ⫽ 188); and
d
DM (n ⫽ 106).
0.797) and IGT (P ⫽ 0.099) after adjusting for other variables.
For 30/15 ratio, it was inversely related to IGT (P ⫽ 0.029)
and DM (P ⫽ 0.019) but not IFG (P ⫽ 0.124). HRDB was not
independently associated with IFG (P ⫽ 0.906), IGT (P ⫽
0.248), and DM (P ⫽ 0.846). For frequency domain, LF power
was not related to any glycemic status, including IFG (P ⫽
0.937), IGT (P ⫽ 0.413), and DM (P ⫽ 0.403). In contrast, HF
power was inversely associated with IGT (P ⫽ 0.014) and DM
(P ⫽ 0.003). IGT (P ⬍ 0.001) and DM (P ⬍ 0.001) were the
positively associated factors of the square root of LF/HF
ratio. However, both the HF power (P ⫽ 0.237) and the
square root of LF/HF ratio (P ⫽ 0.760) were not independently related to isolated IFG after adjusting for other factors.
Discussion
It is well known that the function of the autonomic nervous
system in cardiovascular control is affected in people with
diabetic neuropathy, as manifested by the disturbance of
heart rate control (2). Our results revealed that there was a
significant impairment of the parasympathetic modulation
of the heart, shown by a decreased SDNN, 30/15 ratio, and
HF power in DM subjects. The results are compatible with
other studies (13, 14, 22–24). However, the LF power, a major
quantitative marker of the sympathetic modulation of the
heart, was not significantly different among our NGT, isolated IFG, IGT, and DM subjects. These data suggest that the
parasympathetic dysfunction is the major cause of altered
CAF in diabetic subjects. The exact mechanism underlying
diabetic autonomic neuropathy is still poorly understood,
TABLE 2. Comparisons of clinical variables among subjects with NGT, isolated IFG, IGT, and DM
Age (yr)
Male (%)
BMI (kg/m2)
SBP (mm Hg)
DBP (mm Hg)
HR (beats/min)
Physical activity (met-h/wk)a
Fasting glucose (mmol/liter)
HbA1c (%)
Cholesterol (mmol/liter)
Triglyceride (mmol/liter)a
HDL-C (mmol/liter)
Hypertension (%)
Current alcohol use (%)
Current smoking (%)
NGT
(n ⫽ 983)
Isolated IFG
(n ⫽ 163)
IGT
(n ⫽ 188)
DM
(n ⫽ 106)
P value
38.6 ⫾ 13.7
46.8
23.0 ⫾ 3.3
112.8 ⫾ 15.3
68.9 ⫾ 9.1
64.4 ⫾ 11.1
62.7 ⫾ 90.6
4.9 ⫾ 0.4
4.9 ⫾ 0.5
4.9 ⫾ 1.0
1.2 ⫾ 0.8
1.4 ⫾ 0.4
7.1
12.7
21.6
46.0 ⫾ 14.1
49.1
24.4 ⫾ 3.7
118.3 ⫾ 17.2
72.7 ⫾ 9.6
67.2 ⫾ 11.3
65.2 ⫾ 59.6
5.8 ⫾ 0.3
5.1 ⫾ 0.5
5.0 ⫾ 1.0
1.4 ⫾ 1.0
1.3 ⫾ 0.3
12.3
12.9
17.8
49.2 ⫾ 13.9
44.0
25.0 ⫾ 3.9
123.8 ⫾ 19.5
73.7 ⫾ 11.2
69.5 ⫾ 11.7
54.3 ⫾ 93.0
5.3 ⫾ 0.6
5.1 ⫾ 0.7
5.2 ⫾ 1.0
1.7 ⫾ 0.9
1.3 ⫾ 0.3
20.1
13.6
18.5
55.7 ⫾ 12.7
54.9
25.6 ⫾ 3.6
128.9 ⫾ 21.1
76.5 ⫾ 10.4
71.4 ⫾ 13.3
34.9 ⫾ 38.4
8.8 ⫾ 3.4
7.5 ⫾ 2.4
5.3 ⫾ 1.4
2.5 ⫾ 3.6
1.2 ⫾ 0.4
31.9
15.0
25.7
⬍0.001
0.327
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
0.691
0.501
HR, Average of two seated heart rates; met-h, metabolic equivalent-hours; SBP/DBP, average of two seated systolic/diastolic blood pressures.
a
Kruskal-Wallis test.
3888
J Clin Endocrinol Metab, October 2007, 92(10):3885–3889
Wu et al. • Cardiac Autonomic Function in IGT and IFG
TABLE 3. Comparisons of CAF among subjects with NGT, isolated IFG, IGT, and DM
SDNN (msec)
30/15 ratio
HRDB (beats/min)
LF power (msec2)
HF power (msec2)
Square root of LF/HF ratio
NGT
(n ⫽ 983)
Isolated IFG
(n ⫽ 163)
IGT
(n ⫽ 188)
DM
(n ⫽ 106)
P value,
ANOVA
39.5 ⫾ 24.3
1.10 ⫾ 0.13
18.6 ⫾ 8.1
796.8 ⫾ 436.7
382.0 ⫾ 201.3
1.61 ⫾ 0.79
33.1 ⫾ 18.8a
1.07 ⫾ 0.10
15.7 ⫾ 8.4b
779.6 ⫾ 433.6
343.7 ⫾ 196.5
1.68 ⫾ 0.75
29.6 ⫾ 17.2b
1.06 ⫾ 0.11b
15.6 ⫾ 8.4b
801.9 ⫾ 438.7
289.9 ⫾ 201.3b
2.12 ⫾ 1.39b,d
23.5 ⫾ 15.6b,c
1.04 ⫾ 0.09b
11.9 ⫾ 6.6b,c,e
733.8 ⫾ 417.4
255.7 ⫾ 186.6b,c
2.21 ⫾ 1.58b,d
⬍0.001
⬍0.001
⬍0.001
0.553
⬍0.001
⬍0.001
Comparisons were made by Bonferroni post hoc test.
a,b
Compared with NGT: a P ⬍ 0.01; b P ⬍ 0.001.
c,d
Compared with isolated IFG: c P ⬍ 0.01; d P ⬍ 0.001.
e
Compared with IGT: e P ⫽ 0.001.
although the impact of metabolic changes on neural circulation causing reduced blood flow and hypoxia could be
important factors in the development of neuropathy (25).
Population-based study on the CAF in IGT subjects is
scarce (14). The Hoorn Study has shown that IGT subjects
suffered a higher risk of having a lower 25th percentile of
SDNN (14). Based on the multivariate analysis, our study
revealed that IGT is associated with a lower 30/15 ratio and
HF power but with an increased LF/HF ratio. Both the Hoorn
study and our study observed that CAF was altered in IGT
subjects, although the indicators of CAF that were used differed. The literature shows that IGT is associated with microvascular complications, such as retinopathy (26), nephropathy (26), and neuropathy (27). In addition, IGT
subjects are at great risk of mortality (28, 29) and have an
increased incidence of ischemic heart disease and cerebrovascular disease independent of progression to DM (29).
Because cardiac autonomic dysfunction is strongly associated with an increased risk of cardiac events (3–5) and overall
mortality (3, 6), the possibility that altered CAF is one of the
underlying mechanisms of cardiovascular morbidity and
mortality in IGT subjects needs further investigation.
In our study, CAF in subjects with isolated IFG was not
different from that identified in NGT subjects after adjustments for other variables. The Framingham Heart Study
showed that IFG subjects had a lower SDNN and LF and HF
power than NGT subjects (3), but the IFG subjects had a
higher FPG criterion (6.1– 6.9 mmol/liter) than our subjects.
Only FPG, not concomitant with 2-h PG, was used to classify
the subjects into NGT, IFG, and DM groups, so the IFG
subjects may have IGT and even DM (17, 18). Therefore, the
IFG subjects of the Framingham Heart Study may be more
hyperglycemic and at an advanced stage of the prediabetes/
diabetes course than our isolated IFG subjects. This may
explain the inconsistency between our study and the Framingham Heart Study. The ARIC and our study adopted a
lower IFG criterion of an FPG of 5.6 – 6.9 mmol/liter and
showed there was no difference in SDNN between those with
IFG and NGT, although the ARIC study didn’t exclude the
influence of IGT and DM in IFG subjects (16). In addition, our
FIG. 1. The ␤-coefficient and 95% confidence interval (CI) for the effect of IFG, IGT, and DM on CAF with reference group of NGT from multiple
linear regression analysis on the basis of weight (inverse of the selection probability). Dependent variables are HRV shown by SDNN, 30/15
ratio, HRDB, LF power, HF power, and square root of LF/HF ratio, respectively. Independent variables are age, gender, BMI, plasma cholesterol,
triglyceride, HDL-C, hypertension, isolated IFG vs. NGT, IGT vs. NGT, DM vs. NGT, and physical activity level. *, P ⬍ 0.05; †, P ⬍ 0.01; ‡,
P ⬍ 0.001.
Wu et al. • Cardiac Autonomic Function in IGT and IFG
study revealed that NGT and isolated IFG subjects didn’t
differ significantly in the frequency domain of HRV, such as
HF power, LF power, and LF/HF ratio, although the ARIC
study didn’t perform a power spectral analysis of HRV.
Therefore, the CAF was not apparently altered in subjects
with isolated IFG.
This study provides the epidemiological evidence that an
altered CAF is present in both IGT and DM subjects, but not
IFG subjects, after carefully controlling for confounding factors. By mapping the CAF across the different glycemic
groups, from NGT, then to prediabetes, and finally to DM,
our study reveals that IGT subjects had a decreased parasympathetic modulation of the heart, shown by HF power
and 30/15 ratio, resulting in a shift toward augmented sympathetic tone shown by an increased LF/HF ratio. This impairment also occurs in subjects with DM. Thus, the parasympathetic tone declined with an autonomic imbalance
shifting toward augmented sympathetic tone during the development from NGT to IGT and finally DM. In contrast, the
autonomic impairment is not apparent in IFG subjects. In
conclusion, DM and IGT subjects had an impaired CAF independent of other cardiovascular risk factors. However, the
risk of altered CAF is not significant in subjects with isolated
IFG.
Acknowledgments
Received October 4, 2006. Accepted July 25, 2007.
Address all correspondence and requests for reprints to: Chih-Jen
Chang, Department of Family Medicine, National Cheng Kung University Hospital, 138, Sheng Li Road, Tainan, 70441, Taiwan, Republic of
China. E-mail: [email protected].
This study was supported by grants from the National Science Council, Taiwan, Republic of China (NSC 87-2314-B-006-084, NSC 89-2314B-006-043, and NSC 92-2314-B-006-117).
Disclosure Statement: The authors have nothing to disclose.
J Clin Endocrinol Metab, October 2007, 92(10):3885–3889
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
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