Serum fructose levels are independently associated with
hyperuricemia in PCOS
As shown in Table 2, the
prevalence of hyperuricemia in the PCOS group was 42.12%, which was
significantly higher than that in the control group (12.03%).
Specifically, among all the groups, PCOS women with hyperuricemia had
the highest serum fructose levels, and there was no difference in serum
fructose levels between the hyperuricemia and non-hyperuricemia
subgroups of control women (P > 0.05).
Then, we evaluated the clinical
factors contributing to the risk of hyperuricemia in women with PCOS
(Table 3). After adjusting for confounding factors affecting
hyperuricemia via univariate logistic regression analysis, including
age, BMI, HOMA-IR, free testosterone, HDL-C, and triglycerides, elevated
serum fructose levels were strongly associated with a high risk of
hyperuricemia in PCOS (P = 0.001; OR, 1.380; 95% CI,
1.207–1.577; Table 3).
Discussion
In this study, we reported for
the first time that elevated serum uric acid in women with PCOS strongly
and positively correlated to serum fructose, and serum fructose is an
independent risk factor for hyperuricemia in women with PCOS. In
addition, PCOS patients with metabolic dysfunction are usually found to
have higher serum fructose and uric acid levels and there is a strong
and positive association between elevated uric acid levels and fructose
levels. These observations first suggested a link between elevated serum
uric acid and fructose metabolic dysfunction in PCOS and
fructose-associated elevation of uric acid may play a key role in
PCOS-related metabolic disorders.
As reviewed by Taskinen et al., fructose influences several metabolic
pathways which result in the generation of uric
acid.22 In the liver, fructose is primarily
phosphorylated to fructose 1-phosphate, significantly decreasing
intracellular phosphate and adenosine triphosphate levels. This decrease
stimulates adenosine monophosphate deaminase (AMPD), which catalyzes the
degradation of AMP to inosine monophosphate, producing uric
acid.23 Fructose also stimulates uric acid synthesis
from amino acid precursors24 and competes with uric
acid for renal excretion, reducing the rate of uric acid excretion and
increasing blood uric acid levels.25 Although these
studies have provided preliminary insights into the mechanism of
fructose metabolism to produce uric acid, to date, no study has
investigated the relationship between elevated fructose and uric acid in
PCOS. Our studies have first confirmed the close and positive
association between elevated serum uric acid and fructose levels in
PCOS. Elevated serum uric acid levels may reflect an underlying disorder
of fructose metabolism in patients with PCOS that further emphasize the
potential and critical clinical role of measuring serum uric acid levels
in routine practice.
In recent years, the treatment of PCOS not only aims at its
hyperandrogenemia and infertility symptoms, but also focuses on its
metabolic disorders. An interesting finding of this study is that PCOS
patients with metabolic disorders showed higher serum fructose and uric
acid levels, with a strong positive correlation. Previous studies
provided evidence to support our results. High-fructose is associated
with several PCOS-associated metabolic disorders, including
dyslipidemia, insulin resistance, weight gain, and cardiovascular
effects.26 Uric acid is a product of fructose
metabolism and involved in reproductive and endocrine metabolic
disorders.27 Mounting evidence has shown that uric
acid promotes the development of insulin resistance, lipid metabolism
disorders, and metabolic syndrome.28 Notably, fructose
metabolism can induce hyperuricemia reduces NO levels in endothelial
cells and induces insulin resistance.29 Moreover, uric
acid regulates hepatic steatosis and insulin resistance through the
NLRP3 inflammasome.30 Collectively, the potential role
of fructose-associated elevation of serum uric acid in PCOS may be its
effects on the metabolic disorders of PCOS. These preliminary results
open new avenues toward improving our understanding of the biological
role of fructose and uric acid in the metabolic disorder of PCOS.
The major strength of this study is that this is the first study to
evaluate the relationship between serum uric acid and fructose levels in
PCOS. Another strength of this study is the application of RCS, a
flexible and powerful approach, to analyze the linear/non-linear
relationship between fructose and uric acid in participants with
different metabolic statuses. We further confirmed that elevated serum
uric acid levels were positively correlated with serum fructose levels
in PCOS with metabolic disorders, whereas no correlation was found in
the controls. Additionally, our study still had several limitations.
Although various biochemical measurements associated with PCOS have been
considered, other possible covariates (such as diet, smoking, and
ethnicity) were not evaluated and the mechanisms underlying the elevated
fructose and uric acid levels in women with PCOS remain unclear which
need to be clarified in follow-up research.