Insulin sensitivity is associated with blood pressure
response to sodium in older hypertensives
Donald R.
Dengel,
Robert V.
Hogikyan,
Michael D.
Brown,
Scott G.
Glickman, and
Mark A.
Supiano
Division of Geriatric Medicine, Department of Internal Medicine, and
the Geriatric Research, Education and Clinical Center, Ann Arbor
Veterans Affairs Medical Center, Ann Arbor, Michigan 48105
 |
ABSTRACT |
The purpose of this study was to determine
whether sodium-resistant hypertensives are more insulin resistant and
whether dietary sodium restriction improves insulin sensitivity in
older hypertensives. Insulin sensitivity was assessed by a frequently
sampled intravenous glucose tolerance test to determine the insulin
sensitivity index (SI) after 1 wk each of low- (20 mmol · l
1 · day
1)
and high- (200 mmol · l
1 · day
1)
sodium diets in 21 older (63 ± 2 yr) hypertensives. Subjects were
grouped on the difference in mean arterial blood pressure (MABP)
between diets [sodium sensitive (SS):
5-mmHg increase in MABP
on the high-sodium diet (n = 14);
sodium resistant (SR): <5-mmHg increase in MABP on the high-sodium
diet (n = 7)]. There was no
dietary sodium effect on fasting plasma insulin or
SI. An analysis of variance
indicated a significant (P = 0.0002)
group effect, with SS individuals having lower fasting plasma insulins on the low- (13 ± 2 vs. 27 ± 3 µU/ml) and high- (12 ± 2 vs. 22 ± 3 µU/ml) sodium diets compared with SR individuals.
Similarly, there was a significant (P = 0.0002) group effect in regard to SI, with SS individuals having
significantly higher SI on the low- (3.26 ± 0.60 vs. 0.91 ± 0.31 µU × 10
4 · min
1 · ml
1)
and high- (3.45 ± 0.51 vs. 1.01 ± 0.30 µU × 10
4 · min
1 · ml
1)
sodium diets compared with SR individuals. We conclude that SR
individuals exhibit a greater degree of insulin resistance than SS
individuals and that dietary sodium restriction fails to improve
insulin sensitivity regardless of sodium sensitivity status.
aging
 |
INTRODUCTION |
IT HAS BEEN SUGGESTED that high dietary sodium
intake may contribute to the development of hypertension (15). Although
epidemiological and clinical studies support an association between
dietary sodium intake and blood pressure (13), there is great variation
in blood pressure responses to changes in sodium intake. This variation in the blood pressure response to the modulation of dietary sodium intake has led to the classification of individuals on the basis of
their sensitivity to sodium (24, 27). Weinberger et al. (27) reported
that ~25% of normotensive individuals increase their blood
pressure in response to sodium loading and are classified as sodium
sensitive. However, the proportion of individuals who are sensitive to
the effects of sodium loading on blood pressure increases to >50% in
hypertensive individuals. Although the change in blood pressure in
response to increased dietary sodium intake is normally distributed,
there is a shift in this distribution toward a greater increase in
blood pressure in older individuals as well as those with hypertension
(26).
In addition to changes in blood pressure, dietary sodium restriction
has been reported to increase insulin sensitivity in young, healthy,
normotensive nondiabetic Caucasian males (8). In contrast to these
results, studies in young lean normotensive males (23) and older
hypertensives (6, 16) have reported that dietary sodium restriction had
no effect on insulin sensitivity. Additionally, Lind et al. (16)
reported that insulin sensitivity, as measured when the subject was on
the high-sodium diet, was significantly related to the difference in
standing blood pressure between the two different sodium diets, i.e.,
sodium-resistant subjects had a greater degree of insulin resistance.
In contrast to these observations, Rocchini et al. (19) reported that
sodium-resistant young normotensive and hypertensive subjects were more
insulin sensitive.
The discrepancies in studies that have examined the effect of dietary
sodium restriction on insulin sensitivity may be due to differences in
subject populations, especially with respect to differences in sodium
sensitivity status. To date, most of these studies examined the effect
of dietary sodium restriction in a young healthy normotensive
population, which in general is sodium resistant (27). Such studies
have not been conducted in older, overweight, sedentary hypertensives,
who are more insulin resistant and might have a greater propensity for
dietary sodium-exacerbated changes in glucose homeostasis. In addition,
on the basis of the results of Lind et al. (16), it would appear that
those individuals who are sodium resistant might also be insulin
resistant compared with those who are sodium sensitive.
The purpose of the present study was to test the hypotheses that
1) sodium-resistant hypertensives
would be more insulin resistant than those who are sodium sensitive,
and 2) decreased dietary sodium
intake would increase insulin sensitivity in older hypertensive individuals.
 |
MATERIALS AND METHODS |
Subjects.
Twenty-one subjects (8 males and 13 females) with mild hypertension
were recruited for study. Subjects were recruited through newspaper
advertisement, from the University of Michigan Turner Geriatric Clinic,
and from the Human Subjects Core of the University of Michigan
Geriatrics Center. All subjects were community dwelling and in good
health apart from their hypertension.
Subjects were screened before participation with a medical history and
physical examination, a complete blood count, routine chemistries, and
urinalysis. Individuals were excluded from the study if they had
clinically significant concomitant medical illness, such as cardiac,
renal (serum creatinine >135 mmol/l), hepatic, or gastrointestinal
disease, or required medications that might affect glucose metabolism,
blood pressure, or renal function. Also excluded were individuals with
a recent history of smoking or drug or alcohol abuse, or clinically
relevant mental disorders. Absence of diabetes mellitus, according to
World Health Organization criteria (29), was confirmed in all subjects
by a 2-h 75-g oral glucose tolerance test. The presence of hypertension
was defined in patients who were receiving antihypertensive treatment
or had a seated systolic blood pressure >140 mmHg and/or a
seated diastolic blood pressure >90 mmHg.
General study.
After a screening visit to determine their eligibility for
participation as described above, subjects signed an informed consent form approved by the University of Michigan Institutional Review Board.
Hypertensive subjects who were being treated with antihypertensive medications were tapered off their medications and were studied after a
4-wk period during which no antihypertensive medications were taken.
Subjects were randomized in a double-blind design to begin either a 20 or a 200 mmol · l
1 · day
1
sodium diet, which they consumed over a 7-day period. All meals during
the 7-day sodium diet period were prepared by the General Clinical
Research Center Metabolic Kitchen at the University of Michigan. The
two diets were identical in composition except for sodium content and
consisted of 50-55% of calories as carbohydrate, 30-35% as
fat, 15-20% as protein, and 300-350 mg per day of
cholesterol. After completion of the first metabolic tests, the
subjects consumed their own diet for a 1-wk washout period and then
were switched to the alternative sodium diet, which they consumed for a
second 7-day period. Compliance with the diet was monitored by 24-h
urine collections for sodium.
On the 6th day of each sodium diet, intra-arterial blood pressure
measurements were made while the subject rested in the supine position
after a 20-min resting period. Briefly, a 20-gauge 1.25" Insyte
catheter was placed into the brachial artery of the nondominant arm.
The catheter was connected to a pressure transducer (1290A quartz
transducer, Hewlett-Packard, Andover, MA). Mean arterial blood pressure
(MABP) was determined from the electronically integrated area under the
MABP curve from the Marquette telemetry system (Marquette Electronics
Series 7700, Marquette Electronics, Milwaukee, WI). Blood pressure
measurements were made over a 1-h period and averaged. Subjects were
classified a priori, utilizing previously published criteria, as either
sodium sensitive or sodium resistant on the basis of their MABP
response to the change in dietary sodium intake. Those individuals who
exhibited a change in MABP
5 mmHg were classified as sodium
sensitive, and those individuals who exhibited a change in MABP <5
mmHg were classified as sodium resistant (21, 24).
Frequently sampled intravenous glucose tolerance test.
On the 7th day of each sodium diet, a frequently sampled intravenous
glucose tolerance test (FSIVGTT) was performed, as previously described
by Bergman (2). In all subjects the FSIVGTT included an infusion of
either tolbutamide or insulin (Humulin R, Eli Lilly, Indianapolis, IN)
to enhance precision of the estimates of insulin action (30). Subjects
were studied in the supine position. Briefly, an intravenous catheter
was inserted into an antecubital vein in one arm for the injection of
tolbutamide or insulin and glucose. Another catheter was inserted in a
retrograde manner into a dorsal hand vein of the contralateral arm,
which was placed in a thermostatically controlled (60°C) warming
box to arterialize venous blood samples for the measurement of glucose
and insulin (12). Catheters were kept patent by a slow infusion of
0.45% saline (<50 ml/h). Beginning 20 min after the insertion of
intravenous lines, three baseline blood samples for glucose and insulin
were obtained, and blood pressure and heart rate were measured at 5-min
intervals. Baseline values were calculated as the mean of these three
measurements for each variable.
Fifty percent glucose (300 mg/kg) was given as an intravenous push over
30 s. Blood samples (3 ml) were collected at 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 70, 80, 90, 100, 120, 140, 160, and 180 min after the glucose bolus. Tolbutamide (137 mg/m2 body surface area) or
insulin (0.02 U/kg) was given intravenously over 30 s, 20 min after the
glucose injection, to further stimulate insulin secretion.
Measurements and calculations.
Blood samples for plasma glucose and insulin were collected into
chilled glass tubes containing heparin sodium, stored on ice, and
separated immediately after each study. Plasma was stored at
70°C until assay. Plasma glucose was measured by the
autoanalyzer glucose oxidase method and plasma insulin by
radioimmunoassay in the Core Laboratory of the Michigan Diabetes
Research and Training Center. Samples from each of the subjects' two
studies were analyzed together in the same assay.
The indexes of insulin sensitivity
(SI) and glucose effectiveness
(SG) were calculated from a
least squares fitting of the temporal pattern of glucose and insulin
throughout the FSIVGTT by use of the MINMOD program (R. N. Bergman,
1989). SI is a measure of the
effect of an increment in plasma insulin to enhance the fractional
disappearance of glucose. SG is a
measure of the fractional glucose turnover rate at the basal insulin
level. The acute insulin response to intravenous glucose
(AIRG) was calculated as the
mean rise in plasma insulin above baseline at 3, 4, and 5 min after intravenous glucose administration.
KG, a measure of glucose
tolerance, is the rate of plasma glucose disappearance calculated as
the least square slope of the natural logarithm of absolute glucose concentration between 5 and 20 min after the glucose bolus (a normal
nondiabetic value for KG is
>1%/min). The reproducibility for the minimal model approach for
determining insulin sensitivity has been reported to be ~16% (1,
10).
Body composition was determined using bioelectrical impedance (RJL
Systems, Mt. Clemens, MI) on two separate occasions. Baseline values
were calculated as the mean of these measurements. Body mass index
(BMI, in kg/m2) was determined
by the subject's weight (kg) divided by the square of his or her
height (m).
Statistical analysis.
Data were analyzed using Statview (Abacus Concepts, Berkeley, CA). An
-level of 0.05 was accepted for statistical significance. Characteristics of the sodium-sensitive and sodium-resistant subject groups were compared using analysis of variance (ANOVA). A two-way ANOVA with group (sodium sensitive and sodium resistant) as one variable and diet (low sodium and high sodium) as the other was utilized to examine within- and between-group differences. Comparisons of plasma glucose and insulin levels during the FSIVGTT between the
sodium-sensitive and sodium-resistant subject groups on each of the
sodium diets were made by use of an ANOVA with repeated measures.
Simple multiple regressions and Pearson correlation coefficients were
calculated between changes in MABP and changes in fasting plasma
insulin levels and insulin sensitivity. To determine whether the
relationship between MABP and SI
was affected by age, gender, body weight, percent fat, or waist-to-hip
ratio, a regression model that included a covariate for each of these
variables was also analyzed. All data are reported as means ± SE.
 |
RESULTS |
Subjects.
Subject characteristics are presented in Table
1. Twenty-one older (63.4 ± 1.7 yr) and
moderately obese (BMI: 28.2 ± 0.9 kg/m2) subjects with essential
hypertension were studied. When the 21 subjects were divided into
sodium-sensitive and sodium-resistant groups on the basis of their
response to the dietary sodium restriction regimen, 14 individuals were
categorized as sodium sensitive and 7 individuals were categorized as
sodium resistant. There were no statistically significant differences
in age, weight, BMI, or percent body fat between the sodium-sensitive
and sodium-resistant groups. The waist-to-hip ratio tended to be higher
in the sodium-resistant group, although this difference was not
statistically significant. There was no significant effect of sodium
status (P = 0.906) or dietary
restriction (P = 0.317) on body weight
(Table 2). Although there was no
significant effect of sodium status on MABP, there was a significant
effect of dietary restriction on MABP
(P = 0.024). Additionally, there was a
significant (P = 0.017) interaction effect of sodium status and dietary sodium on MABP, indicating that the
sodium-sensitive individuals were able to decrease their MABP in
response to the reduction of dietary sodium (116 ± 2 vs. 102 ± 2 mmHg), whereas the sodium-resistant individuals did not (113 ± 3 vs. 114 ± 4 mmHg) (Table 2).
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Table 2.
Body weight, blood pressure, and metabolic parameters of glucose
kinetics in sodium-sensitive and sodium-resistant hypertensives on
low- and high-sodium diets
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The sodium-sensitive group had significantly lower fasting plasma
glucose levels than the sodium-resistant group (Table 2). However,
there was no significant diet effect on fasting plasma glucose. The
sodium-sensitive group had significantly lower fasting plasma insulin
levels than the sodium-resistant group (Table 2 and Fig.
1), and there was no effect of diet on
fasting plasma insulin levels (Fig. 1). The change in MABP due to
dietary sodium restriction tended to correlate with the
fasting plasma insulin level on both the low-
(r = 0.45, P = 0.04) and high-
(r = 0.41, P = 0.06) sodium diets.

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Fig. 1.
Plasma fasting insulin levels on low- (20 meq/day) and high- (200 meq/day) sodium intake in sodium-sensitive ( ) and sodium-resistant
( ) hypertensives. Mean fasting insulin levels are shown by
horizontal bars. Significantly different
(P < 0.01) from sodium-sensitive
group.
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The SI, as determined from modeling of the FSIVGTT results
by MINMOD, was significantly lower in the sodium-resistant than in the
sodium-sensitive group (Table 2 and Fig.
2). No significant diet effect
(P = 0.807) or order of diet effect
(P = 0.35) on SI was identified. In addition, no
order effect (sodium diet) was observed on
SI. When the individual plasma
glucose and insulin values during the FSIVGTT were examined by ANOVA
for repeated measures, a significant
(P < 0.05) group and experimental
treatment effect was observed for both the plasma glucose and insulin
values on the low- and high-sodium diets (Fig.
3). In addition, a significant (P < 0.05) group × experimental treatment interaction was noted for the plasma glucose and
insulin values on both the low- and high-sodium diets. The
sodium-resistant individuals had higher glucose and insulin profiles
than the sodium-sensitive individuals. There were significant
correlations between SI on both
the low- (r = 0.45, P = 0.04) and high-
(r = 0.56, P = 0.008) sodium diets and
the change in MABP (Fig. 4). In addition to
the univariate linear regression analysis, the association between low-
and high-sodium diet SI
values was analyzed after covariance for age, gender, body
weight, percent fat, and waist-to-hip ratio. These regression models
indicated that a positive correlation between
SI on both the low- and
high-sodium diets and MABP remained significant when these variables
were included as covariates.

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Fig. 2.
Sensitivity to insulin index
(SI) as determined using the
insulin-assisted frequently sampled intravenous glucose tolerance test
(FSIVGTT) at low- (20 mmol · l 1 · day 1)
and high- (200 mmol · l 1 · day 1)
sodium intake in sodium-sensitive ( ) and sodium-resistant ( )
hypertensives. Mean fasting insulin levels are shown by horizontal
bars. Significantly different
(P < 0.01) from sodium-sensitive
group.
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Fig. 3.
Plasma glucose and insulin values during the FSIVGTT at low- (20 mmol · l 1 · day 1;
A) and high- (200 mmol · l 1 · day 1;
B) sodium intake in sodium-sensitive
( ) and sodium-resistant ( ) hypertensives. Compared with
sodium-sensitive subjects, sodium-resistant hypertensives had
significantly higher glucose and insulin profiles throughout the
FSIVGTT on both sodium diets (by ANOVA for each,
P < 0.05).
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Fig. 4.
Scattergram and regression line depicting relationship between
SI, as determined using
insulin-assisted FSIVGTT during low- (20 mmol · l 1 · day 1;
A) and high- (200 mmol · l 1 · day 1;
B) sodium intake, and change ( )
in mean arterial blood pressure.
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The KG was significantly lower in
the sodium-resistant than in the sodium-sensitive group (Table 2).
Dietary sodium restriction did not have an effect on
KG in either group. There was no
difference in SG or
AIRG between the two groups (Table
2), nor was there an effect of diet.
The mean 24-h urinary sodium excretion was significantly lower during
the low-sodium diet in both groups, which was appropriate for the
reduction in dietary sodium intake (Table
3). There was a significant decrease in
both plasma chloride and plasma urea levels with the reduction in
dietary sodium. Plasma levels of sodium were significantly lower in the
sodium-sensitive individuals (Table 3). There was no effect of sodium
status or diet sodium on either plasma or urinary creatinine levels
(Table 3). In addition, there was no group or diet effect on creatinine
clearance calculated from the 24-h urine collections (Table 3).
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Table 3.
Plasma and urinary values in sodium-sensitive and sodium-resistant
hypertensives on low- and high-sodium diets
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 |
DISCUSSION |
The primary findings of this study are that
1) sodium-resistant hypertensive
individuals exhibit a greater degree of insulin resistance than those
who are sodium sensitive and 2)
dietary sodium restriction in older, moderately obese hypertensives
does not enhance insulin sensitivity regardless of sodium-sensitivity status.
To the best of our knowledge, this is the first study to report that
sodium-resistant hypertensives are more insulin resistant than their
sodium-sensitive counterparts. Lind et al. (16) previously reported a
significant relationship between the difference in standing blood
pressure due to changes in dietary sodium intake and insulin
sensitivity measured during a high-sodium diet. The results of the
present study and those of Lind et al. are in contrast to those
reported by Rocchini et al. (19) and Sharma et al. (23), who reported
the opposite relationship between insulin sensitivity and sodium
sensitivity, namely that sodium-sensitive individuals were insulin
resistant compared with individuals who were categorized as sodium
resistant. A reason for the difference between results from the present
study and that of Lind et al. and those of Sharma et al. and Rocchini
et al. is unknown. However, it is possible that differences in subject
population and classification of sodium sensitivity may explain the
difference in results. In the present study, we examined the effect of
dietary sodium restriction on insulin sensitivity in an older
hypertensive population, whereas Rocchini et al. examined this question
in young nonobese hypertensive and normotensive adults and Sharma et
al. studied this same question in a young lean normotensive population.
It has been demonstrated that older individuals are insulin resistant
compared with younger individuals (25) and that normotensive
individuals are more sensitive to insulin than a comparable group of
hypertensive individuals (7). Therefore, one would expect the
population in the studies of Rocchini et al. and Sharma et al. to be
more sensitive to the effects of insulin than the older population we
examined in the present study. Another possible explanation may be in
the classification of sodium-sensitivity status. Rocchini et al.
assessed sodium sensitivity using the Weinberger protocol, which
involves the intravenous administration of 2 liters of saline followed
by sodium, and volume depletion induced by a low-sodium diet and
furosemide (27). A sodium-sensitive individual was defined as one with a decrease in mean blood pressure, with volume depletion
10 mmHg. In
the present study, we assessed sodium sensitivity by the change in
supine intra-arterial blood pressure in response to a change in dietary
sodium. Although Sharma et al. used a similar dietary protocol to
assess sodium sensitivity, this study used a 3-mmHg change in blood
pressure measured using an automatic oscillometric blood pressure
device to classify subjects as either sodium sensitive or sodium
resistant. However, if the criteria of Sharma et al. for determining
sodium sensitivity are applied to our subject population, only two of
our subjects would switch sodium-sensitivity status, and the
sodium-sensitive individuals would still have a significantly greater
SI value than the sodium-resistant
individuals.
The mechanism for this difference in insulin sensitivity between
sodium-resistant and sodium-sensitive individuals is unclear. DeFronzo
et al. (5) demonstrated that insulin has an effect to enhance renal
sodium reabsorption. On the basis of this information, it might have
been expected that subjects with higher insulin levels would retain
more sodium on a high-sodium diet and increase their blood pressure.
However, we observed that the more insulin-resistant subjects who had
higher fasting plasma insulin levels exhibited the least change in
blood pressure on the high-sodium diet. Previously, we have
demonstrated that sodium-sensitive individuals have an increase in
glomerular filtration rate in response to an increase in dietary
sodium, whereas sodium-resistant individuals have no change in renal
hemodynamics in response to the change in dietary sodium (28). Rocchini
(18) postulated "selective" insulin resistance to explain the
finding that sodium-sensitive individuals were resistant to
insulin-mediated glucose uptake, yet appeared to retain the normal
natriuretic effect of insulin. Perhaps given the age-related decrements
in renal function (20), insulin resistance among the older hypertensive
population might extend to include resistance to the effects of insulin
on renal hemodynamics and sodium reabsorption. Bigazzi et al. (3)
reported a decrease in renal plasma flow and an increase in filtration
fraction in sensitive individuals who consumed a high-sodium diet. In
the present study we observed no significant differences in creatinine clearance due to sensitivity to sodium or to the change in dietary sodium. Creatinine clearance is a crude measure of renal hemodynamics, so further studies are needed to examine the role of renal hemodynamics in explaining the differences in sensitivity to sodium and insulin. We
also examined the effect of dietary sodium restriction on body weight
and observed that neither sodium-sensitive nor sodium-resistant individuals had a significant change in body weight with the change in
dietary sodium. Another potential explanation for the sodium-resistant group being more insulin resistant is that the sodium-resistant individuals in this study tended to have a higher waist-to-hip ratio.
An increase in central adiposity has been linked to the decline in
insulin sensitivity that is observed with aging (4). Therefore, the
tendency for increased central adiposity in the sodium-resistant
individuals might contribute to their decreased sensitivity to insulin.
In the present study we did not observe any enhancement in insulin
sensitivity during dietary sodium restriction in these older
hypertensives, regardless of sodium sensitivity status. These results
confirm our previous findings that dietary sodium restriction does not
change insulin sensitivity in an older hypertensive population (6). In
contrast to the lack of an effect of dietary sodium intake on insulin
sensitivity in our study, Donovan et al. (8) reported a significant
increase in insulin sensitivity during dietary sodium restriction in
young healthy normotensive individuals. The difference between results from the present study and others (6, 11, 16, 23) and those of Donovan
et al. is not clear. Potential explanations include differences in
subject population, in the methods used to measure insulin sensitivity,
or in the duration or sodium intake of the sodium diet periods. In the
present study, the subjects consumed each diet for a 7-day period,
whereas in the study by Donovan et al. the sodium diet duration was for
5 days. Recently, Fliser et al. (11) examined the effect of the
duration of high- (200 mmol/day) and low- (20 mmol/day) sodium diets by
comparing a 3-day vs. a 7-day diet duration with respect to
insulin-mediated glucose disposal in young healthy normotensive
subjects. The authors observed that there was a significant decrease in
insulin-mediated glucose disposal on the low- compared with the
high-sodium diet after 3 days. However, in the group that consumed the
same two sodium diets for a 7-day period each, there was no difference
in insulin-mediated glucose disposal rates between the two sodium
diets. The results of Fliser et al. suggest that the improvement in
tissue sensitivity to insulin during dietary sodium restriction may be
an acute event and that studies examining the chronic effect of dietary
sodium on glucose metabolism need to be carried out over a longer time.
Although previous studies have reported a change in fasting plasma
insulin and glucose levels with a modulation in dietary sodium (9, 14,
17, 22, 23) similar to that of our previous study (6) and the results
of Donovan et al. (8), we did not observe any significant alteration in
either fasting plasma insulin or glucose levels with the change in
dietary sodium. Of interest is the significantly higher fasting plasma
insulin levels in the sodium-resistant individuals. These higher
fasting plasma insulin levels in the sodium-resistant individuals are
likely explained by their greater degree of insulin resistance. Lind et
al. (16) reported that those individuals with the lowest standing blood
pressure also displayed the highest fasting plasma insulin levels.
However, the results of the present study and those of Lind et al. are
in contrast to those of Sharma et al. (23), who reported no difference
in fasting plasma insulin levels between sodium-resistant and
sodium-sensitive young normotensives.
In conclusion, our results indicate that sodium-resistant hypertensive
individuals have a greater degree of insulin resistance than those with
sodium-sensitive hypertension and that there is overall a positive
correlation between blood pressure response to dietary sodium loading
and sensitivity to insulin. Second, these results support previous
studies that have reported that dietary sodium restriction does not
enhance insulin sensitivity. Thus, it appears that in addition to their
inability to lower their blood pressure in response to a reduction in
dietary sodium, sodium-resistant individuals exhibit a greater degree
of insulin resistance than their sodium-sensitive counterparts.
 |
ACKNOWLEDGEMENTS |
We thank all the subjects who volunteered; the nursing and dietary
staffs at the University of Michigan General Clinical Research Center
for their assistance with the research studies; Marla Smith for
technical assistance; and Dr. Jeffrey Halter for review of the
manuscript.
 |
FOOTNOTES |
This study was supported by National Institutes of Health Research
Scientist Development Award in Aging KO1 AG-0072301 (to D. R. Dengel);
the Department of Veterans Affairs Medical Research Service (M. A. Supiano); the Geriatric Research, Education and Clinical Center at Ann
Arbor, University of Michigan, Claude D. Pepper Older Americans
Independence Center (AG-08808, to D. R. Dengel, R. V. Hogikyan, and M. A. Supiano); and the University of Michigan Clinical Research Center
(RR-00042).
Address for reprint requests: D. R. Dengel, Ann Arbor VA Medical
Center, GRECC (11G), 2215 Fuller Road, Ann Arbor, MI 48105.
Received 15 July 1997; accepted in final form 12 November 1997.
 |
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