BASIC RESEARCH

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Thiazide Diuretics Exacerbate Fructose-Induced

Metabolic Syndrome
Sirirat Reungjui,* Carlos A. Roncal,* Wei Mu,* Titte R. Srinivas,* Dhavee Sirivongs,
Richard J. Johnson,* and Takahiko Nakagawa*
*Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, Florida; and Division
of Nephrology, Khon Kaen University, Khon Kaen, Thailand

ABSTRACT
Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic
syndrome. Thiazide diuretics are frequently used in these patients for treatment of hypertension, but
they also exacerbate metabolic syndrome. Rats on high-fructose diets that are given thiazides exhibit
potassium depletion and hyperuricemia. Potassium supplementation improves their insulin resistance
and hypertension, whereas allopurinol reduces serum levels of uric acid and ameliorates hypertension,
hypertriglyceridemia, hyperglycemia, and insulin resistance. Both potassium supplementation and treatment with allopurinol also increase urinary nitric oxide excretion. We suggest that potassium depletion
and hyperuricemia in rats exacerbates endothelial dysfunction and lowers the bioavailability of nitric
oxide, which blocks insulin activity and causes insulin resistance during thiazide usage. Addition of
potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic
syndrome.
J Am Soc Nephrol 18: 2624 2731, 2007. doi: 10.1681/ASN.2007040416

The metabolic syndrome (MS) is a constellation of

risk factors for cardiovascular disease and type 2
diabetes and consists of abdominal obesity, hypertriglyceridemia, low HDL cholesterol, high BP, insulin resistance, and hyperglycemia.1,2 Endothelial
dysfunction and hyperuricemia also are closely associated with MS.3,4
Hydrochlorothiazide (HCTZ) is beneficial in
patients with hypertension because it reduces morbidity and mortality, especially the frequency of
stroke and congestive heart failure.5,6 As a result,
thiazides are recommended as the first-line therapy
for hypertension.6 However, many patients with
hypertension have MS. In turn, HCTZ usage, although critical in the management of hypertension,
can have several adverse effects, such as electrolyte
disorders (hypokalemia, hyponatremia, and hypomagnesemia), hyperuricemia, hyperlipidemia, and
impairment of glucose metabolism in addition to
volume depletion.710 These adverse effects result in
the development or exacerbation of MS. Although
low-dosage thiazides have led to a reduction of these
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ISSN : 1046-6673/1810-2624

adverse effects, they increase the incidence of new onset of diabetes9 and can be associated with hypokalemia, hyperuricemia, and hyperlipidemia.11
Understanding the precise mechanisms by which
HCTZ exacerbates MS is important. Some evidence
suggests that thiazide-induced hypokalemia may mediate insulin resistance.12,13 In addition, experimental
hyperuricemia can cause endothelial dysfunction,3,14
hypertension,15 and hyperinsulinemia.3,16 Furthermore, we recently reported that hyperuricemia causes
the development of MS, and allopurinol, which lowers
uric acid levels, improves these features of MS in fructose (F)-fed rats.3 We therefore hypothesized that hyReceived April 6, 2007. Accepted June 20, 2007.
Published online ahead of print. Publication date available at
www.jasn.org.
Correspondence: Dr. Sirirat Reungjui, current address is Division
of Nephrology, Faculty of Medicine, Khon Kaen University, Khon
Kaen, Thailand 40002. Phone: 66-43-363746; Fax: 66-43347542; E-mail: sirirt_a@kku.ac.th
Copyright 2007 by the American Society of Nephrology
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pokalemia and hyperuricemia may be primary mechanisms by

which the thiazides facilitate the MS and that acceleration of MS
by thiazides may be prevented by potassium (K) supplementation
and allopurinol.
In this study, we administered thiazides to rats with MS,
because this syndrome is common in patients with hypertension and it is important to determine whether thiazides can
exacerbate its features. Although there are various models of
MS in animals, we selected the F-induced model of MS. Indeed, the increasing incidence of MS in humans in the past two
decades coincides with a marked increase in F intake.17,18 Importantly, that high F consumption causes features of the MS
has been documented in clinical studies.19 21 Similarly, high-F
diets cause MS in rodents, including hypertension, insulin resistance, and hypertriglyceridemia.3,22,23 In this study, we hypothesized that HCTZ use exacerbates F-induced MS and examined the role of hypokalemia and hyperuricemia in this
process.

RESULTS

BASIC RESEARCH

Figure 1. SBP at weeks 4 and 16. The rats receiving F develop

hypertension. HCTZ reduces the SBP. KCL further reduces BP at
week 16. Similarly, allopurinol reduces BP reduction at both weeks 4
and 16. Data are means SD. P at least 0.05 *versus normal diet,
&
versus F, $versus FHCTZ, and #versus FHCTZKCL.

HCTZ Reduced Systolic BP but Aggravated F-Induced

MS

Body Weights

All rats were pair fed to eliminate effects of food intake on the
results, which can influence glucose, insulin, and triglyceride
levels. Although this will not allow us to determine whether
thiazides can cause weight gain because access was not ad libitum, it did allow us to determine whether thiazides alter triglyceride and glucose levels independent of effects on food
intake. As such, the average body weights were similar in all
groups at week 20, as shown in Table 1.
F-Induced Features of MS in Rats

At week 4, the F-fed rats developed early features of MS, including hypertension (Figure 1), hypertriglyceridemia (normal diet 125 55 versus F 325 104 mg/dl; P 0.001) and
hyperuricemia (normal diet 1.7 0.3 versus F 2.2 0.4 mg/dl;
P 0.01). Serum cholesterol was significantly higher at week
14 (Figure 2). No significant difference in serum glucose was
observed between the F group and the normal diet group (Figure 2).

HCTZ use reduced systolic BP (SBP) in the FHCTZ group

compared with the F group at weeks 4 and 16 (Figure 1). The
level of serum K was significantly lower in the FHCTZ and
FHCTZallopurinol groups at week 20, whereas all
HCTZ-treated rats also developed hypomagnesemia (Table
1). An increase of serum HCO3 was also observed (F
23.0 0.9; FHCTZ 24.7 1.1; FHCTZKCL 25.6
1.8; FHCTZallopurinol 25.7 1.5 mEq/L; all P 0.05
versus the F group).
HCTZ use did not exacerbate MS early at week 4; the metabolic profile of the F group and the FHCTZ group was similar at this time. However, HCTZ aggravated insulin resistance
(Figure 3) and hyperuricemia at week 14 (F 2.2 0.5 versus
FHCTZ 2.7 0.5 mg/dl; P 0.04) and at week 20 (F 2.2
0.6 versus FHCTZ 2.8 0.6 mg/dl; P 0.02). Serum glucose
was also increased by HCTZ at week 14 (F 150 10 versus
FHCTZ 176 13 mg/dl; P 0.006) and at week 20 (F 160
26 versus FHCTZ 186 22 mg/dl; P 0.02). Although se-

Table 1. Renal function, serum K, serum Mg2, and urinary uric acid excretion evaluated at week 20 of the study
Groups
Body weight (g)
BUN (mg/dL)
Cr (mg/dL)
Serum K (mEq/L)
Serum Mg2 (mg/dL)
Urine protein/Cr
Urine uric acid (mg/d)
Uric acid clearance (ml/min)

N
543 45
13.8 1.4
0.44 0.05
4.4 0.2
1.6 0.28
0.24 0.4
2.42 0.4
0.09 0.02

F HCTZ

F HCTZ
KCL

F HCTZ
Allopurinol

565 66
13 2.6
0.43 0.05
4.3 0.1
1.5 0.23
2.29 2.5a
4.07 0.8a
0.13 0.02a

560 88
26.6 14a,b
0.46 0.11
4.0 0.1a,b,d
1.15 0.1a,b
2.53 2.3a
2.93 1.0b
0.08 0.03b

558 58
25.3 6.6a,b
0.44 0.07
4.5 0.3
1.09 0.1a,b
3.18 2.8a
3.67 0.9a
0.11 0.3

557 89
22.5 6.4a,b
0.44 0.05
4.1 0.1a,b,d
1.1 0.1a,b
2.86 2.4a
3.38 1.1a
0.17 0.05a,c,d

Data are expressed as mean SD. N, normal diet group; F, fructose diet group; FHCTZ, fructose diet and hydrochlorothiazide group; FHCTZKCL, fructose
diet and hydrochlorothiazide plus potassium chloride group; FHCTZAllopurinol, fructose diet and hydrochlorothiazide plus allopurinol group.
All P values are at least 0.05. aP versus normal diet; bP versus fructose diet; cP versus FHCTZ; dP versus F HCTZKCL.

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KCL rats at week 16 (FHCTZ 136 4 versus FHCTZKCL 131 5 mmHg; P 0.04), whereas no effect was
observed at week 4 (FHCTZ 129 5 versus FHCTZKCL
127 3 mmHg; P 0.05). By insulin tolerance test, serum
glucose was not decreased despite insulin administration in the
FHCTZ group, whereas insulin-induced reduction of serum
glucose was observed in the FHCTZKCL group (Figure 4).
These data suggest that K supplementation improves insulin
sensitivity, which was deteriorated by fructose with HCTZ.
Compatibly, K supplementation tended to lower serum glucose at week 20 (FHCTZ 186 22 versus FHCTZKCL
166 20 mmHg; P 0.06). No significant change of serum
uric acid and serum triglycerides was observed in the FHCTZKCL group compared with the FHCTZ group.

Figure 2. Time courses of serum uric acid (A), serum glucose (B),
serum cholesterol (C), and serum triglycerides (D). The rats receiving
F developed hyperuricemia and hypertriglyceridemia throughout
the study. Hypercholesterolemia was detected at week 14. The
combination of HCTZ with F causes more hyperuricemia and hyperglycemia as shown at weeks 14 and 20. Serum cholesterol and
triglyceride are numerically higher with HCTZ use but did not reach
statistical significance. KCL tends to reduce serum glucose at week
20 (P 0.06). Allopurinol treatment significantly reduces serum uric
acid and triglycerides at all time points and serum glucose at week
20. Data are means SD. P at least 0.05 *versus normal diet,
&
versus F, $versus FHCTZ, and #versus FHCTZKCL.

Lowering Uric Acid with Allopurinol Improved

Hypertension, Hypertriglyceridemia, Hyperglycemia,
and Insulin Resistance

Allopurinol treatment significantly reduced the level of serum

uric acid in the FHCTZ group. In addition, allopurinol significantly reduced SBP (Figure 1), and serum triglycerides
were also significantly lower than the FHCTZ group at weeks
4, 14, and 20 (Figure 2).
Insulin resistance was improved by allopurinol (Figures 3
and 4). In addition, serum glucose was significantly lower at
week 20 (FHCTZ 186 22 versus FHCTZallopurinol
166 14 mg/dl; P 0.04).
To investigate further the role of uric acid, we examined the
correlation between uric acid and other factors. When individual data on rats were examined at week 20, serum uric acid
positively correlated with serum triglycerides, serum cholesterol, and serum glucose (Figure 5). Furthermore, there was a
significant correlation between serum uric acid and SBP at
week 4 (r 0.53, P 0.003) and serum insulin at week 14 (r
0.42, P 0.009).
Insulin and Other Factors

At week 14, serum insulin concentrations in normal, F, FHCTZ,

Figure 3. QUICKI at week 14. The combination of FHCTZ

significantly lowers insulin sensitivity than the normal diet or the F.
Treatment with allopurinol improves insulin sensitivity. KCL tends
to improve insulin sensitivity, but this was NS. Data are means
SD. P 0.05 *versus normal diet, &versus F, and $versus FHCTZ.

rum triglycerides were higher in the FHCTZ group, they did

not reach statistical significance (Figure 2).
K Supplementation Reduced SBP and Improved Insulin
Resistance

K supplementation significantly reduced SBP in FHCTZ2726

Journal of the American Society of Nephrology

Figure 4. The insulin tolerance test at week 18. Blood glucose

levels were not lowered by insulin in rats receiving F with or
without HCTZ, consistent with insulin resistance. In contrast, KCL
and allopurinol treatment improve the insulin response similar to
that observed with the normal diet group. Data are means SD.
P at least 0.05 *versus normal diet, &versus fructose diet, and
$
versus FHCTZ.
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FHCTZKCL, and FHCTZallopurinol groups were

1846 452, 2561 1286, 3449 1200, 3058 1514, and 2319
971 pg/ml, respectively. Significant differences of serum insulin
were detected between FHCTZ and normal (P 0.002) and
borderline significance between FHCTZ and FHCTZallopurinol (P 0.05). Serum insulin levels positively correlated not
only with serum glucose but also with serum triglycerides and
serum cholesterol (Figure 5), suggesting an association between
insulin resistance and dyslipidemia.24,25
Renal Function and Urinary Excretion of Sodium, K,
and Uric Acid

Although there was no significant difference in serum creatinine between groups, an increased urinary protein excretion
by F suggests renal dysfunction. However, an elevation of
blood urea nitrogen (BUN) in all HCTZ-treated groups
(groups 3, 4, and 5) could be attributed to volume depletion
induced by HCTZ, because F did not raise BUN.
With respect to urinary electrolytes, HCTZ significantly increased daily urinary sodium excretion at week 1 (normal
0.4 0.2; F 0.5 0.1; FHCTZ 0.8 0.4; FHCTZKCL
0.8 0.2; and FHCTZallopurinol 0.9 0.3 mEq/d; all P
0.05 versus normal or F). Urinary K excretion was also significantly higher in the FHCTZ group (1.5 0.4 mEq/d) and the
FHCTZallopurinol group (1.4 0.3 mEq/d) as compared
with the F group (1.2 0.1 mEq/d). Because of K supplementation, the FHCTZKCL group had normal serum K level
with high urine K (3.1 1.1).
The F group developed hyperuricemia (Figure 2) with

Figure 5. Correlations of various metabolic factors in fructose/

HCTZ-induced MS in the rat.
J Am Soc Nephrol 18: 2624 2731, 2007

BASIC RESEARCH

higher urinary uric acid excretion per day and uric acid clearance compared with the normal group (Table 1), which suggested an increase of uric acid production. Similar to that observed in humans, HCTZ enhanced hyperuricemia (Figure 2),
which could be attributed to a reduction of urinary uric acid
excretion (Table 1). Allopurinol acutely reduced 32.3% of urinary uric acid excretion compared with the FHCTZ group
during the first week (P 0.05), which could be due to a
reduced production of uric acid by allopurinol. However, it is
of note that urinary uric acid excretion and uric acid clearance
increased during the chronic phase despite allopurinol use
(Table 1).
K Supplementation or Allopurinol Increase Urinary
Nitric Oxide Excretion

Urine nitrate/nitrite excretion is a marker of nitric oxide (NO)

bioavailability as well as endothelial function.26,27 F decreased
urine nitrate/nitrites, which were further lowered by HCTZ.
However, K supplementation or allopurinol treatment increased urinary nitrate/nitrite excretion (Figure 6).

DISCUSSION

The principal new finding in this study is that we can show

experimentally that correcting the serum K and uric acid abnormalities in F-induced MS in rats can largely prevent the
metabolic abnormalities that are associated with thiazides. The
beneficial effects of these treatments were associated with an
increase in urine nitrite/nitrates, suggesting the involvement of
endothelial dysfunction on the development of MS with thiazide usage.
Hypokalemia occurs in 6.5 to 50% of patients receiving diuretics,28 30 with the average reduction of serum K from thiazides reported at approximately 0.3 to 1.1 mEq/L.6,31,32 Previous studies suggested that hypokalemia may be a factor causing
hyperglycemia, hyperinsulinemia, and insulin resistance in pa-

Figure 6. Urine nitrate/nitrite level. The levels of urinary nitrate

and nitrite in rats receiving F are lower than that observed in the
normal diet group. HCTZ induces a further reduction of urinary
nitrate and nitrite. KCL and allopurinol treatment increases the
level of urinary nitrate and nitrite compared with the FHCTZ.
Data are means SD. P at least 0.05 *versus normal diet,
&
versus F, and $versus FHCTZ.
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tients receiving thiazides, because these features can be improved with K supplements.13,33 It also has been shown that K
depletion, even without frank hypokalemia, can cause insulin
resistance.34 In our experiments, HCTZ produced a significant
reduction in serum K (0.3 mEq/L), although this did not reach
the criteria of hypokalemia (serum K 3.5 mEq/L). Our important finding is that this mild K depletion was significantly
associated with exacerbation of hyperglycemia, insulin resistance, and a reduction of urine NO excretion, all of which were
corrected by K supplementation. The observation that K supplements prevented the reduction of urine NO in F-fed rats
receiving HCTZ is consistent with an improvement in endothelial function. K supplementation has been shown to act as
an endothelium-derived hyperpolarizing factor35 and release
NO to preserve endothelial function,36 whereas K depletion
was found to attenuate endothelial-dependent vasorelaxation.37 In turn, an inhibition of endothelial NO is known to
cause insulin resistance.38
Unlike glucose, F is the only sugar that rapidly increases
serum uric acid in humans as well as rodents.3 Recently, we
found that F-induced hyperuricemia has a causal role in the
pathogenesis of MS.3 This study demonstrated that HCTZ enhanced hyperuricemia in rats receiving a high-F diet by reducing urinary uric acid excretion, although F likely increases the
production of uric acid. Decreased urinary uric acid excretion
could be due to an increase in uric acid reabsorption in proximal tubule, which may be mediated by thiazide-induced volume contraction.39
Another important finding is that the lowering of serum
uric acid by allopurinol was associated with an improvement of
the features of MS. We also found that a lowering of uric acid
by allopurinol was associated with an increase in urinary NO
excretion. Given that uric acid inhibits endothelial NO bioavailability as well as endothelial function,3,14,40 a lowering of
uric acid could improve endothelial function in this model.
Collectively, these findings suggest that hyperuricemia, by virtue of reducing NO, plays a role in the pathogenesis of the MS
aggravated with HCTZ.
The inhibition of uric acid production by allopurinol
likely accounts for the reduction of urinary uric acid excretion during the first week. However, with long-term allopurinol treatment, the reduction in uric acid excretion was
not observed. Although the precise mechanism remains unknown, hyperuricemic rats are known to develop renal vasoconstriction with a reduction of renal blood flow, and this
is reversed by allopurinol.41 In turn, an increase in renal
blood flow will result in increased uric acid excretion.42 In
this scenario, by improving endothelial dysfunction and renal blood flow, the lowering of uric acid could paradoxically
enhance excretion.
The effect of high F intake on insulin sensitivity is still
debated. As recently reviewed,43 some groups have observed
that healthy individuals develop insulin resistance after high
F consumption, whereas others have reported no effect on
glucose metabolism as well as insulin sensitivity. One reason
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Journal of the American Society of Nephrology

for this discrepancy is dosage. For example, when 1000 kcal

is given, insulin resistance develops in 1 wk19; when 864
kcal/d is consumed, insulin resistance is observed only in
organs with high fructokinase activity (liver, fat cells) and
takes 4 wk20; and when lower dosages are given, no insulin
resistance is observed, even after 1 mo.21 Similar situations
occur in the rat. With high dosages (60% F), insulin resistance occurs within 4 to 8 wk3; with dosages similar to that
in the current American diet (15% total energy intake), it
takes slightly more than 1 yr.44 However, the rat is more
resistant because it has low uric acid levels; indeed, if uricase
is inhibited, then 20% F will induce hyperinsulinemia rapidly.45 Furthermore, F, by virtue of increasing the circulation of fatty acids, may lead to the ectopic deposition of fat
in liver and skeletal muscle that will cause insulin resistance
indirectly.46 This indirect induction of insulin resistance by
F could also account for the discrepancy in some of these
studies. Because F and its metabolites fructose-3-phosphate
and 3-deoxyglucosone cause oxidative stress and nonenzymatic glycation,47 the polyol pathway could also be involved
in development of MS.
This study demonstrates that HCTZ aggravates the MS in
F-fed rats and that K supplementation and reducing uric acid
levels may provide some protection. Nevertheless, it will be
important to determine whether similar protection can be provided by these maneuvers in humans. In this regard, we are
involved in a randomized, controlled trial to determine
whether lowering of uric acid will improve features of MS associated with thiazide use in black individuals with stage 1
hypertension.

CONCISE METHODS
All animal studies were approved by the University of Florida Institutional Animal Use and Care Committee.

Pilot Studies
Because variable dosages of HCTZ have been commonly used in
other studies (e.g., 3 to 80 mg/kg per d48,49), we performed pilot
studies to determine the minimum adequate dosage of HCTZ for
this study. Because the aim of study was to examine the role of
hypokalemia on adverse effects of HCTZ, we identified the lowest
dosage that can reduce BP along with a mild reduction of serum K.
We therefore gave three different dosages of HCTZ (Sigma-Aldrich, St. Louis, MO) to normal rats. As a result, we found that 10
mg/kg per d HCTZ is the lowest dosage that reduced BP and induced mild hypokalemia.

Experimental Protocol

Male Sprague-Dawley rats (150 to 200 g; Charles River, Wilmington, MA) were placed on a standard diet (Harlan, Madison, WI) for a 5-d run-in period, then the rats were divided
into five groups (n 8) with similar body weight and baseline
blood chemistry: Group 1: Normal standard diet (Harlan);
group 2 (F): 60% fructose diet (Harlan); group 3 (FHCTZ):
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In addition to 60% fructose diet, HCTZ 10 mg/kg per d was

supplied in drinking water; group 4 (FHCTZKCL): 60% F
diet with HCTZ and 1% K chloride (KCL) in drinking water;
the concentration of KCL in drinking water was increased at
weeks 5 (1.5% KCL), 15 (1.75% KCL), and 17 (2% KCL) to
maintain normal serum K level through the whole study; and
group 5 (FHCTZallopurinol): 60% F diet plus HCTZ and
allopurinol 150 mg/L (Sigma-Aldrich) in drinking water.
We pair-fed rats to ensure equivalent caloric intake, thereby
avoiding the influence of different food intake on the metabolic abnormalities. Body weight was measured weekly. At
weeks 1, 4, 14, and 20, metabolic cages were used for urine
collection overnight, where water but no food was freely accessed. After 4 h of fasting, serum was also collected from the
tail vein at weeks 4, 14, and 20. At the end of week 20, rats were
killed.
Tail-Cuff BP Measurement

SBP was measured in conscious rats with tail-cuff sphygmomanometer (Visitech BP2000, Apex, NC) at weeks 4 and 16 as
described previously.3

BASIC RESEARCH

Statistical Analyses
All data are shown as means SD. One-way ANOVA (SPSS 14.0;
SPSS, Chicago, IL) and post hoc multiple comparisons were used to
determine the significance between the mean of multiple groups with
the least-significant difference test for equal and Dunnett test for unequal variances. The homogeneity of variance was clarified by Levene
test. The paired and unpaired t tests were used to compare the continuous variables of the specific two groups. Pearson correlation was
used to address potential associations between groups. Statistical significance was defined as P 0.05.

ACKNOWLEDGMENTS
The work was supported by funding from the National Institutes of
Health grants DK-52121, HL-68607, and HL-79352 and funds from
Gatorade. S.R. is supported by a fellowship from the Anandamahidol
Foundation of Thailand.

DISCLOSURES
Biochemical Measurements
Serum and urine K concentrations were determined with the atomic
absorption spectrophotometer (Perkin-Elmer 306, Downers Grove,
IL). By use of an autoanalyzer (VetAce; Alfa Wassermann, West Caldwell, NJ), the routine chemistries including glucose, cholesterol, triglycerides, uric acid, BUN, and creatinine were measured in serum. In
addition, urine protein concentration and urine creatinine were determined.

Serum Insulin and the Quantitative Insulin Sensitivity

Check Index
Fasting serum glucose and insulin were obtained at week 14. Serum
insulin was determined with the rat insulin ELISA kit (Crystal Chem,
Chicago, IL). Quantitative Insulin Sensitivity Check Index (QUICKI)
is a mathematical model based on log-transformed fasting plasma
glucose and insulin values by equal 1/(log [glucose] log [insulin]).
QUICKI predicts insulin sensitivity, with lower values representing
more insulin resistance. QUICKI shows a good correlation with the
hyperinsulinemic-euglycemic clamp method, especially in individuals with impaired glucose tolerance.50

Insulin Tolerance Test

At week 18, 0.75 U/kg recombinant human insulin (Novolin; Novo
Nordisk, Princeton, NJ) was administered intraperitoneally after rats
had been fasted for 16 h. Blood glucose was determined on tail blood
via hand-held blood glucose monitor (OneTouch; Johnson & Johnson, Milpitas, CA) at five points: 0, 15, 30, 45, and 60 min after insulin
injection.

Measurement of Urinary NO
Urine was determined for NO by using the nitrate/nitrite colorimetric
assay kit (Cayman Chemical Co., Ann Arbor, MI).
J Am Soc Nephrol 18: 2624 2731, 2007

T.N., S.R., and R.J.J. are listed as inventors on several patent applications
related to uric acid and cardiovascular disease from the University of Florida or
University of Washington. R.J.J. is also on the Scientific Board of Nephromics,
Inc.

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See related editorial, The Fructose Nation, on pages 2619 2621.

Thiazides and Metabolic Syndrome

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