The main finding of the study was that higher UA levels were associated positively with BMI, triglycerides, urea, and CRP and inversely with MMI. According to the gender, the main predictors for UA increase were BMI and muscle mass for men. Waist circumference, creatinine, and muscle mass (positively); and HDL-c (negatively) were associated for women.
UA serum concentrations are maintained through the synthesis and excretion of urate [40
]; hence, creatinine and serum urea, which are considered to be glomerular function markers, are directly related to UA concentrations, particularly due to the urate excretion relationship. Choe et al.
, 2008 [41
] reported that creatinine has strong influence on urate concentrations. Rathmann et al.
(2007) investigated UA concentrations in a population consisting of black and white adults for ten years and identified an independent relationship of creatinine and urate [42
Creatinine serum concentration was one of the main UA-related factors for females. In the odds-ratio model (Table ), altered creatinine increased the chances of hyperuricemia, but this fact occurred only in the first adjustment of the model. When the body-composition components were added, the effect was lost. On the other hand individuals with altered urea showed approximately 2.5 more chances of increasing UA, regardless of the influence from other factors, including glomerular filtration rate, which means that mechanisms independently of excretion can influence this relation.
The increase in uricemia distribution quartiles did not follow age increase. It is usually reported that, as age advances, a gradual reduction in glomerular filtration occurs, which results in plasma retention of solutes that are normally excreted by the kidneys [43
]. In the present study, age ranged from 21 to 82 years, but most individuals were 40 to 60 years old and probably showed little variability in glomerular filtration. Additionally, the adjustment for glomerular filtration rate was made.
The increase in uricemia distribution quartiles was accompanied by increase in body adiposity markers (weight, BMI, WC and % body fat). Altered WC was positively associated with urate concentrations; however, when fitted for other MS components, the effect was lost, thus showing that WC is indirectly associated with UA, since individuals with abdominal adiposity could present MS and/or alteration in its components, and these could be responsible for affecting UA. It is believed that TG is the main MS component influencing UA, as it was the only factor that remained significant after all adjustments.
Other studies showed the relationship between WC or abdominal adiposity and UA increase [44
], reporting that visceral fat is more related to UA increase than subcutaneous fat [46
]. Adipose tissue produces various cytokines, including leptin, and the probable explanation for the association between WC and hyperuricemia would be the association found by Bedir et al
., (2003) [48
] and Fruehwald-Schultes et al
., (1999) [49
], where UA serum concentrations are independently related to leptin. Two mechanisms could explain such relationship. The first would be the influence of leptin on the renal function, which decreases renal UA excretion. In the second mechanism, UA could modulate leptin concentrations, thus increasing its gene expression or decreasing its excretion [49
BMI above 25 kg/m2
was one of the main components associated with UA increase both in the fitted models and in the multiple regression analysis for males, and it also showed significant correlation with uricemia. BMI showed a positive relation with leptin concentrations [50
], which is a factor leading to UA increase.
Additionally, individuals with high BMI may show insulin resistance, TG alteration and high blood pressure, and all these factors are related to UA increase [12
]. In our study, insulin sensitivity was not measured; however, the analyses were fitted for SAH and TG, and the values remained significant. This showed that independent mechanisms from these two factors could explain such relation, probably to insulin resistance.
UA increase is observed in individuals with insulin resistance, probably because hyperinsulinemia would cause lower renal UA excretion [51
]. Besides, insulin could also indirectly affect UA, since there is an association between hyperinsulinemia and hypertriglyceridemia.
In the present study, individuals with altered TG showed approximately 2.5 more chances of UA increase, regardless of other variables (body composition. gender, inflammation, dyslipidemia, MS, and SAH). Some studies show that high plasma triglyceride concentrations are related to hyperuricemia [52
]. One of the explanations for such relation would be that, during the TG synthesis, there would be a greater need for NADPH for the de novo
synthesis of fatty acids [53
]. Matsuura et al.
(1998) report that the synthesis of fatty acids in the liver is related to the de novo
synthesis of purine, thus accelerating UA production [45
In the present study, UA concentrations were negatively determined by MM (kg) in males and females. The hypothesis would be the negative correlation existing between MM and inflammation [56
], since an association between UA increase and inflammatory markers has been reported [57
]. However, in our study, muscle mass was fitted for inflammation (CRP), and the influence of muscle mass on UA remained. Possibly, other mechanisms would influence the association between muscle reduction and UA increase, such as oxidative stress.
A recent study observed an inverse relation between MMI and UA in healthy individuals older than 40 years [58
]. The authors believe that increased urate serum concentrations would be a causal factor for sarcopenia, especially through increased inflammation and oxidative stress [58
]. During the sarcopenic process, reactive oxygen species (ROS) and oxidative stress increase, and one of the mechanisms for ROS increase would be the activation of the xanthine oxidase metabolic pathway, which increases UA production and the superoxide radical [59
]. In the present study, oxidative stress was not evaluated, and it may be a causal factor for such relation between UA and MMI; however, further studies analyzing the cause and effect between these two factors and their main mechanisms are necessary.
A positive association was found between UA and CRP (inflammation), regardless of body composition (hyperadiposity and/or sarcopenia), gender, age and the presence of MS and its components, which means that there are a direct relation between these two factors. Another study showed a positive association between inflammation and UA, but no adjustment was performed to observe whether the effect would remain the same [60
studies showed that UA exerts a pro-inflammatory effect, thus stimulating the production of interleukin-1, interleukin-6 the tumor necrosis factor [61
Individuals with higher CRP concentrations showed increased UA; however, UA is positively associated with total plasma antioxidant capacity, thus showing beneficial effects. On the other hand, deleterious relations of urate, such as the inverse association with adiponectin and the positive relation with E-selectin, were previously observed [62
]. Such associations can show that UA may increase in order to enhance total plasma antioxidant capacity against moderate oxidative and inflammatory stress, thus being a protective feature against factors related to cardiovascular diseases. It is also noteworthy that UA may be deleterious in high concentrations [21
], which shows the importance of maintaining urate values within normality.
Reduced HDL-c was one of the main factors responsible for UA increase (negative association) in females. This fact was observed by the backward stepwise multiple regression analysis. The negative correlation between HDL-c and AU was previously described [60
], and it has been recently shown that the higher the urate concentration, the smaller the size of HDL-c and LDL-c particles, which provides a greater atherogenic profile [60
]. However, our group has shown that, when the adjustment for body composition and SM components is performed, the association between UA and HDL-c is lost [16
], which was also observed in the present study after adjustment. The probable mechanisms for the inverse association between these two factors would be the relation existing between HDL-c reduction and insulin resistance [63
It is expected that individuals with high UA will have more chances of presenting MS [52
]. MS is associated with increased oxidative stress [64
], and it known that UA is a potent antioxidant [3
]. Thus, it can be supposed that urate increase could result from the defense mechanism from such oxidative stress [65
]. These factors further enhance our results, since the factors associated with UA (BMI, MMI, urea, TG and CRP) remained significant even after adjustment for MS.
In the present study, diet did not show direct influence on UA, but inadequate diet, conjointly with lack of physical activity, could alter body composition (higher adiposity), and such alteration would change UA. Additionally, an indirect relation of high carbohydrate intake was observed through the possible alterations in TG and/or glycemia.
The intake of protein, meat and legumes, which could be related to increased purine intake, was not related to UA concentrations, thus agreeing with the literature [13
]. Some studies showed that high purine intake does not influence UA, since a purine-rich diet would be responsible for increasing only 1 to 2 mg/dL of UA [66
]. Although the present study evaluated the intake of protein-source foods, an exclusive investigation on purine-source foods was not performed. Hence, further studies are required in order to learn about the actual effects of the intake of purine-rich foods on urate concentrations.
A significant weak and inverse correlation was observed (r
−0.11) between the intake of dairy products and UA, but when fitted for gender, BMI and VCT, the significance was lost. Although the present study did not observe such relation, other investigations reported an inverse association between dairy products and UA [13
], which is explained by the fact that milk proteins (lactalbumin and casein) showed a uricosuric effect [69
Based on our data, lifestyle-modification conducts targeted at lean-mass maintenance and fat-mass reduction and concern about dietary composition are suggested in primary care for uricemia increase in non-uremic individuals.
This was a cross-sectional study, and some cause/effect relationships cannot be possibly confirmed, but only whether or not an association between the studied factors exists. The dietary intake investigation on the individuals was performed only on one day, and a food recall for at least three weekdays would ideal, since there may be dietary variations that were not analyzed. Some dietary factors were not evaluated, such as the intake of alcohol, purine and caffeinated drinks, which are known for their interference with UA values [14
]. Insulin resistance was not measured, and that would be important for this type of analysis, since some UA increase mechanisms are involved with this factor. Furthermore, medication intake and smoking status were not controlled.