In this cross-sectional study, we observed a nonlinear relationship between UHR and ALT in short stature children and adolescents, with a turning point of ALT of 10.93%. When UHR levels were greater than 10.93%, UHR was positively associated with ALT.
We observed a positive correlation between UHR and ALT. Previous studies that have directly explored UHR and ALT are limited, but UHR is a new metabolic predictor with high sensitivity and specificity compared to other metabolic syndrome diagnostic criteria[19]. Regarding the association between UHR and ALT, Mehmet Ali Kosekli et al. observed that UHR was positively associated with ALT through a controlled study[24]. Moreover, a positive association between UHR and ALT was also reported in Chinese lean individuals by Ya-Nan Zhang et al. [29]. These results are consistent with the findings of our study.
Uric acid is a product of purine metabolism, and elevated serum uric acid levels are associated with the deterioration of metabolic status[30]. Low HDL-C is also associated with a poor metabolic status and is even a marker of metabolic syndrome[31]. The combination of these two metabolic parameters is UHR, a more useful predictor of metabolic deterioration[32]. Since hepatic steatosis is associated with metabolic syndrome[33, 34], and ALT reflects an excessive deposition of hepatic fat[35], this could explain the increase in ALT with increased UHR.
Uric acid is synthesized by xanthine oxidase during purine metabolism and is excreted through the kidney. Thus, elevated uric acid levels are a result of increased synthesis and decreased excretion[20, 36]. In addition, eating habits greatly affect the production and metabolism of uric acid[37]. Among the participants in our study, there were many unbalanced eating habits, such as picky eating, partial eating, and excessive intake of high-sugar drinks, which may lead to elevated uric acid levels. Elevated uric acid levels contribute to the development of adverse conditions. Previous results suggest a strong association between uric acid levels and metabolic syndrome in children and adolescents, and various mechanisms have been proposed to explain this correlation[38]. HDL-C has the effects of reverse transport of cholesterol to reduce atherosclerosis, anti-inflammation, anti-thrombosis, antiapoptosis and vasodilation[39]. An analysis of a large health and nutrition survey from the United States indicated that low levels of serum HDL are important in the development of metabolic syndrome and identified it as the most powerful predictor[40]. Thus, low serum HDL-C levels with high UA levels reflect a worse metabolic status.
The liver is an important organ of human metabolism. Ageing of the liver and abnormal accumulation of fat can rupture hepatocytes, releasing ALT into the blood. Measurement of ALT levels is a basic test for screening for liver disease and assessing disease progression. However, serum ALT is not only a sensitive indicator for assessing liver function but is also closely related to metabolic factors. In China, through a 7-year follow-up cohort study, even if ALT remained within the range of normal reference values, it was an independent predictor of metabolic syndrome[41]. In other words, both UHR and ALT are associated with metabolic syndrome, and interestingly, our study found a nonlinear relationship between UHR and ALT, with ALT levels increasing with UHR when UHR was above 10.92%, while at lower values, no relationship was observed. Simple linear evaluation may underestimate this correlation. It is well known that obesity is a major risk factor for metabolic deterioration. BMI is a useful indicator to assess obesity and nutritional status[42]. We found a close relationship between ALT and BMI. However, after adjustment for BMI, the UHR remained independently associated with ALT.
Furthermore, UHR, as a novel marker of metabolic syndrome[43], has been used to assess type 2 diabetes mellitus[20, 32], hepatic steatosis[44], Hashimoto's thyroiditis[45], and the control of MAFLD[24]. UHR was also reported to be associated with poor collateral circulation in chronic total occlusion (CTO) patients and to have important predictive value for cardiovascular mortality in patients living on peritoneal dialysis[46, 47].Evidence has shown that short stature children and adolescents also have metabolic abnormalities, so it is necessary to evaluate UHR levels in the diagnosis and treatment of short stature[18].
Study strengths and limitations
The present study has several advantages. First, UHR is a newly proposed novel predictor of metabolism, with previous studies on UHR being few and all in adults; this is the first study of the relationship between UHR and ALT levels in short children and adolescents.Second, in this study, we used smooth curve fitting to find a nonlinear relationship between UHR and ALT levels rather than assuming a simple positive correlation.
However, this study has some limitations. First, we were unable to determine the causal relationships due to the cross-sectional study design. Second, this study was conducted in a homogeneous population of short-stature children and adolescents in China, so our results cannot be extrapolated to other groups. Third, there are many factors affecting uric acid and cholesterol, such as dietary status. In the future, we intend to use questionnaires on dietary habits for a more thorough assessment.