The influence of metabolic syndrome on serum uric acid level and its

The influence of metabolic syndrome on serum uric acid level and its

584
Probl Hig Epidemiol 2009, 90(4): 584-587
The influence of metabolic syndrome on serum uric acid level
and its relation to renal function
Wpływ zespołu metabolicznego na stężenie kwasu moczowego w surowicy oraz na funkcję nerek
Paweł Samborski 1/, Paweł Bogdański 2,3/, Marta Olszanowska 1/, Magdalena Łuczak 2,3/
1/
2/
3/
Studencke Koło Naukowe przy Klinice Chorób Wewnętrznych, Zaburzeń Metabolicznych i Nadciśnienia Tętniczego,
Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
Klinika Chorób Wewnętrznych, Zaburzeń Metabolicznych i Nadciśnienia Tętniczego, Uniwersytet Medyczny im. Karola
Marcinkowskiego w Poznaniu
Pracownia Edukacji, Diagnostyki i Leczenia Otyłości, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
Wprowadzenie. Zespół metaboliczny (MS) często wiąże się z podwyższonym
stężeniem kwasu moczowego w surowicy (SUA). Według ostatnich badań,
wysoki poziom SUA przyspiesza procesy miażdżycowe i może przyczyniać
się do rozwinięcia niewydolności nerek.
Introduction. The metabolic syndrome (MS) is often associated with an
elevated level of serum uric acid (SUA). According to recent studies, the
increased SUA concentration accelerates atherogenesis and may contribute
to progressive renal disease.
Cel pracy. Ocena stężenie SUA i klirensu kreatyniny oraz poszukiwanie ich
wzajemnych zależności u chorych z ZM.
Aim. To evaluate the SUA level and creatinine clearance and their
relationship in patients with the metabolic syndrome.
Materiał i metody. Badana grupa objęła 55 pacjentów (27 kobiet i 28
mężczyzn) ze zdiagnozowaną otyłością. U 35 badanych rozpoznano
dodatkowo zespół metaboliczny według kryteriów Adult Treatment
Panel III. Średni wiek badanej grupy wynosił 41,7±12,6 lat. Pacjentów
poddano badaniu przedmiotowemu z oceną masy ciała, wzrostu, obwodu
w pasie i ciśnienia krwi. Badania laboratoryjne (glikemia na czczo, profil
lipidowy, stężenie kwasu moczowego i kreatyniny) wykonano za pomocą
standardowych metod. Klirens kreatyniny oceniono za pomocą wzoru
Cockrofta i Gaulta.
Material and methods. The study group consisted of 55 patients (27
females and 28 males, mean age 41.7±12.6 years) with obesity. In
35 patients MS was diagnosed according to the Adult Treatment Panel
III criteria. The subjects underwent physical examination including the
evaluation of body weight, height, waist circumference, blood pressure.
Biochemical analyses (fasting glycaemia, serum lipid parameters, uric acid
and creatinine levels) were assessed using commercial tests. Creatinine
clearance was calculated with the Cockroft-Gault formula.
Wyniki. Stężenie kwasu moczowego było wyższe u pacjentów z zespołem
metabolicznym (5,52±1,19 vs. 4,86±1,16 mg/dl). Wszyscy badani
mieli podwyższony klirens kreatyniny (143,4±41,3 ml/min/1,73 m2 vs.
166,6±48,9 ml/min/1,73 m2, p=NS). Stwierdzono pozytywną korelację
pomiędzy klirensem kreatyniny a BMI (r=0,54; p<0,05). Nie zaobserwowano
korelacji stężenia kwasu moczowego i klirensu kreatyniny.
Wnioski. Stężenie kwasu moczowego w surowicy krwi u chorych ze
zdiagnozowanym zespołem metabolicznym jest wyższe niż u osób
z izolowaną otyłością. Podwyższone wartości poziomu kwasu moczowego
mogą się przekładać na wzrost ryzyka wystąpienia niewydolności nerek
w pierwszej grupie.
Results. In the MS group the serum uric acid was elevated in comparison to
the obesity group (5.52±1.19 vs. 4.86±1.16 mg/dl). Creatinine clearance
was increased in both groups (166.6±48.9 ml/min/1.73 m2 in the MS
group vs. 143.4±41.3 ml/min/1.73 m2 in the obesity group, p=NS) and it
correlated positively with BMI (r=0.54, p<0.05). No significant association
between the level of serum uric acid and creatinine clearance was found.
Conclusions. Uric acid serum concentrations are elevated in the metabolic
syndrome in comparison to uncomplicated obesity. The risk of progressive
renal disease may be increased in the first group.
Key words: uric acid, obesity, metabolic syndrome
Słowa kluczowe: kwas moczowy, otyłość, zespół metaboliczny
© Probl Hig Epidemiol 2009, 90(4): 584-587
www.phie.pl
Nadesłano: 20.08.2009
Zakwalifikowano do druku: 20.12.2009
Adres do korespondencji / Address for correspondence
Paweł Samborski
ul. Biskupińska 31, 60-463 Poznań
tel. 660-470-101, e-mail: [email protected]
Abbreviations
Introduction
MS – metabolic syndrome
SUA – serum uric acid
Obesity has recently reached epidemic proportions, also in Poland. According to the results of the
NATPOL PLUS study, over a half of adults in Poland
have incorrect body mass, including 34% of overweight and 19% of obesity cases. 20% of the examined
Samborski P i wsp. The influence of metabolic syndrome on serum uric acid level and its relation to renal function
were diagnosed with the metabolic syndrome (MS)
according to the Adult Treatment Panel III criteria
[1]. Obesity can lead to many serious complications
and biochemical disorders, such as hypertension,
sleep apnoea syndrome, osteoarthrosis or hormonal
disturbances [2].
Patients with excessive body mass, especially coexisting with other disorders in MS, more frequently
develop such serious diseases as cardiovascular disease
and progressive renal disease. Their pathogenesis is
mainly associated with massive atherosclerosis. But
what is the linking element between obesity or MS and
accelerated atherogenesis? The answer is obviously
complicated due to numerous biochemical disorders
and substances responsible for this process. According
to recent studies, one of them is probably serum uric
acid (SUA). Its concentration is usually elevated in
MS compared with a normal population. An increase
of the SUA level in MS may be caused by the influence
of each of its components (Fig. 1). Visceral obesity,
elevated triglyceride concentration, hypertension and
insulin resistance particularly increase the SUA production and retention. Hyperglycaemia and decreased
HDL concentration are also positively correlated with
the SUA level, although the mechanisms responsible
for this process are not clearly defined [3].
For a long time the elevated SUA concentration was
considered to be a graded risk marker of cardiovascular
and renal disease (especially in patients with hypertension, diabetes and heart failure). It was not expected to
play any important causative role in those clinical states.
However, recent studies revealed that it may also contribute to an accelerated progression of atherosclerosis
and thus take part in the pathogenesis of cardiovascular
disease and progressive renal disease. Moreover, harmful
influence of SUA is noticeable even in the upper 1/3 of
the normal physiologic range (>4 mg/dl) [4].
Dangerous impact of an increased SUA level is
multifaceted and not completely discovered. Some
new pathological mechanisms are still being revealed.
Main serious features of hyperuricemia include: stimulating vascular smooth muscle cells proliferation
[5, 6] causing endothelial dysfunction, increasing
underlying vascular inflammation and disturbing
antioxidant–prooxidant redox shuttle. SUA also
interacts with other proatherogenic factors (C-reactive protein, hyperhomocysteinemia) in a synergistic
manner [4, 6].
VISCERAL OBESITY
TRIGLYCERYDE
CONCENTRATION
585
HYPERTENSION
SERUM URIC ACID
CONCENTRATION
IGT
HDL
CONCENTRATION
INSULIN RESISTANCE
Fig. 1. The influence of metabolic syndrome elements and insulin
resistance on serum uric acid concentration
IGT – impaired glucose tolerance; HDL – high density lipoproteins.
Thick arrows – strong influence; thin arrows – lesser influence; dashed
arrows – not clearly defined
Materials and methods
The patients included into the study group were
diagnosed with obesity according to the Body Mass
Index (BMI) higher than 30 kg/m2. Some subjects also
had the metabolic syndrome, established according to
the Adult Treatment Panel III criteria: waist circumference over 102 cm for males, 88 cm for females and at
least two of the following conditions: elevated blood
pressure (≥ 130/85 mm Hg), lowered HDL level
(<40 in males, and <50 mg/dl in females), increased
triglycerides (≥150 mg/dl) and fasting glucose level
(≥110 mg/dl).
The criteria of exclusion were: serious cardiovascular diseases, smoking, uncontrolled hypertension,
secondary hypertension or secondary obesity, variations in body mass greater than 3 kg during the recent
three months, incorrect renal and liver function, acute
or chronic, clinically significant inflammatory process,
an infection during the recent month and alcohol
abuse.
The study group consisted of 55 patients including
27 females and 28 males. They all were obese and 35
of them were diagnosed with MS (tab. I).
Table I. Characteristic of studied groups
Patients with
obesity and MS
n
age (years)
Patients with obesity
without MS
35
20
40.7±10.2
39.1±14.4
NS
11/9
NS
Aim
male/female
17/18
To evaluate the influence of MS on the SUA level
in comparison to uncomplicated obesity. Subsequently
the relation of the SUA concentration to renal function was assessed by calculating creatinine clearance
in both groups of patients.
BMI (kg/m2)
35.1±4.5
(30.5-43,3)
34.7±5.0
(30.4±42.8)
NS
NS – non statistically significant BMI – body mass index
586
The subjects underwent physical examination
including the evaluation of body weight, height, waist circumference and blood pressure. Blood pressure
was measured three times, in a sitting position, with
the use of mercurial sphygmomanometer. Before the
measurement the patients were advised to rest for five
minutes and were not allowed to drink strong tea, coffee or smoke cigarettes for thirty minutes. The sleeve of
a manometer had a rubber cushion twelve centimetres
wide and thirty five centimetres long. In case of an
obese person, a wider sleeve was used. On the basis
of mean value of blood pressure measurements from
three days preceding the blood sample intake (according to valid standards of the Polish Hypertension
Society) mean systolic and diastolic blood pressure
was calculated.
Biochemical analyses
Fasting glycaemia
Glucose was determined in venous blood plasma
using enzymatic method with glucose oxydase and
peroxydase.
Serum lipid parameters
Total cholesterol level, LDL fraction cholesterol,
HDL fraction cholesterol and triglycerides (TG) level
was determined using enzymatic commercial tests.
Total cholesterol (TCH) level was assessed using
enzymatic method with cholesterol esterase, cholesterol oxidase and peroxidase. HDL fraction cholesterol
was assessed with the use of a direct method with the
Cormay HDL-DIRECT set. TG serum concentration
was measured using enzymatic method in visible
light with lipase, glycerol kinase, 3-phosphoglycerol
oxydase and peroxydase. LDL fraction cholesterol was
calculated with the Friedewald formula (37):
Cholesterol LDL (mmol/l) = TCH (mmol/l) – HDL
(mmol/l) – TG (mmol/l)/2,2
This formula was used if TG level was < 4,6
mmol/l
Uric acid
Uric acid serum concentration was determined
using the enzymatic colorimetric method with uricase.
Creatinine levels
Creatinine serum concentration was measured
using the Jaffa colorimetric method.
Creatinine clearance was calculated with the
Cockroft-Gault formula:
Creatinine Clearance = (140 – age) × body weight
(kg) /Plasma creatinine (mg/dl) × 72 × N
N for man =1, for woman =0.85
Probl Hig Epidemiol 2009, 90(4): 584-587
Statistical analysis
The data are shown as mean ± SD. All calculations and statistics were performed with Statistica
for Windows (version 5’97 Edition). Continuous
variables were assessed for normal distribution with
the Shapiro-Wilk test. The groups were compared
by the appropriate test – Student’s test for unpaired
samples. Simple associations between variables will be
calculated as the Pearson correlation coefficient.
Results
In the patients with MS significantly higher concentrations of triglycerides and fasting plasma glucose
were found. The concentration of HDL cholesterol
was significantly lower. There were no differences in
systolic and diastolic blood pressure, total cholesterol
and LDL cholesterol concentrations (tab. II).
Table II. Biochemical parameters in patients with obesity and metabolic
syndrome vs. obese patients without metabolic syndrome
Patients with
obesity and MS
Patients with obesity
without MS
SBP (mmHg)
138.2±7.6
137.1±8.6
NS
DBP (mmHg)
88.1±7.5
87.1±6.0
NS
TCH (mmol/L)
5.3±1.0
5.1±0.9
NS
LDL(mmol/L)
3.1±1.0
3.0±0.7
NS
HDL(mmol/L)
1.2±0.3
1.5±0.3
P<0.01
TG(mmol/L)
2.5±1.6
1.2±0.3
P<0.01
Glucose(mmol/L)
5.3±0.7
4.8±0.4
P<0.01
NS – non-statistically significant
SBP – systolic blood pressure, DBP – diastolic blood pressure, TCH – total
cholesterol, LDL – cholesterol LDL, HDL – cholesterol HDL, TG – triglycerides
In the MS group the serum uric acid concentration
was significantly elevated in comparison to the obesity
group (5.52±1.19 vs. 4.86±1.16 mg/dl, p<0.05).
Creatinine clearance was increased in both groups
(166.6±48.9 ml/min/1.73 m2 in the MS group vs.
143.4±41.3 ml/min/1.73 m2 in the obesity group)
– Fig. 2. However no significant association between
the level of serum uric acid and creatinine clearance
was found (p=NS). There was a positive correlation
between BMI and creatinine clearance (r=0.54,
p<0.05).
CREATININE CLEARANCE (ml/min/1.73 m2)
180
160
140
SERUM URIC ACID LEVEL (mg/dl)
6
166,6
143,4
5,52
4,86
5
120
100
80
4
60
40
20
0
2
3
1
0
MS
Obesity
MS
Obesity
Fig. 2. Difference in creatinine clearance and serum uric acid level in
the presence of metabolic syndrome
Samborski P i wsp. The influence of metabolic syndrome on serum uric acid level and its relation to renal function
Discussion
The study revealed that the SUA concentration is
significantly higher in the population with MS than
in patients with uncomplicated obesity. This result
corresponded with the research of Hikita et al. (2007)
and Chen et al. (2007) [7,3]. According to Chen et al.
(2007), an increase of the SUA level can be associated
with the influence of all MS factors.
In both groups of patients the median SUA concentration was within the physiological range, defined
as ≤7 mg/dl (in men) or ≤6.0 mg/dl (in women) [8].
However, Hayden et al. (2004) suggested that the upper 1/3 of the normal physiologic–homeostatic range
(>4 mg/dl) should be considered as an important
risk factor of accelerated atherosclerosis [4]. From
this perspective both populations, especially the MS
patient group, are at an increased risk of atherosclerotic
complications according to their SUA concentration.
A study done by Feig et al. (2006) revealed that one of
the dangerous consequences of hyperuricemia can be a
progressive renal injury [5]. In this study both patient
groups manifested increased creatinine clearance which
may suggest incorrect renal function. However, there
was no significant correlation between the SUA concentration and creatinine clearance. Perhaps a trial on
a larger population would bring some other results.
587
According to the Abramczyk’s study (2007), the
elevated SUA concentration in patients with hypertension should be lowered. Probably a similar SUAdecreasing treatment should be applied in subjects
suffering from obesity, especially with the coexisting
MS. The treatment should begin with normalization of
MS disorders, firstly by body mass reduction and modification in pharmacological treatment of hypertension
[9]. Apart from that, xanthine oxidase inhibitors are
available.
Conclusions
Patients diagnosed with the metabolic syndrome
are more likely to develop elevated serum uric acid
concentration in comparison with a normal population, as well as subjects with uncomplicated obesity.
Predisposition to increased serum uric acid level
in patients with the metabolic syndrome should be
considered as a potential risk factor for atherosclerosis development and its complications, including
progressive renal disease. Injurious influence of uric
acid is evident not only in hyperuricemia but already
in concentration higher than 4 mg/dl, which is the
upper part of physiologic range.
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