Study subjects.
According to the inclusion and exclusion criteria, The subjects included a total of 1510 children and adolescents with short stature who visited at the Department of Endocrinology, Affiliated Hospital of Jining Medical University from March 1, 2013, and December 31, 2021. Among them, 1029 were male and 481 were female. Collect and organize clinical data that meet the diagnostic criteria of short stature, and conduct cross-sectional analysis. Data of this study are part of the cohort GDDSD study (Growth and Development Diseases in Shandong Province: a cohort follow-up study, http://www.chictr.org.cn, ChiCTR1900026510). Subjects were included and excluded according to the following criteria: Inclusion criteria: The height of each subject is less than − 2 standard deviations compared with the same age, same sex, same ethnic group. Exclusion criteria: patients with abnormal thyroid function, small for gestational age, intracranial tumor, Turner syndrome, Noonan syndrome, Kallman syndrome, congenital heart disease, skeletal dysplasia, received growth hormone therapy, abnormal liver function, and subjects with incomplete data on ALT, UA and HDL. (Table 1).
Table 1
Study population description
| All |
Number | 1510 |
Sex (male %) | 1029 (68.15%) |
Age (years) | 10.38 ± 3.58 |
Height (cm) | 125.86 ± 18.04 |
Height SDS | -2.50 (-2.95–2.21) |
Weight (kg) | 27.94 ± 11.34 |
BMI(kg/m2) | 16.88 ± 3.05 |
SBP(mmHg) | 105.75 ± 12.16 |
DBP(mmHg) | 62.55 ± 8.73 |
IGF-1 (ng/ml) | 171.00 (102.00-258.00) |
GH peak(ng/ml) | 6.96 (4.52–10.52) |
HDL-C (mg/dl) | 53.60(46.83–61.15) |
LDL-C (mg/dl) | 81.99 ± 22.80 |
TC(mg/dl) | 150.32 ± 28.30 |
TG(mg/dl) | 58.48 (46.07–77.53) |
ALT (U/L) | 15.51 ± 9.04 |
FBG (mg/dl) | 86.49 ± 33.47 |
UA (mg/dl) | 4.51 ± 1.21 |
CR (µmol/L) | 40.78 ± 13.77 |
UHR(%) | 8.73 ± 3.31 |
Pubertal stage | |
Prepubertal (%) | 936 (61.99%) |
Pubertal (%) | 574 (38.01%) |
Abbreviations: Height SDS: height standard deviation scores; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; IGF-1: insulin-like growth factor-1; GH peak: growth hormone peak; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol; TC: total cholesterol; TG: triglyceride; ALT: alanine aminotransferase; FPG: fasting plasma glucose; UA: uric acid; Cr: creatinine; UHR: uric acid to high density lipoprotein cholesterol ratio. |
Normally distributed data are presented as the mean ± standard deviation; nonnormal distributed data are presented as median (interquartile range) and categorical data are presented using number (percentage). P < 0.05 was considered to be statistically significant. |
Anthropomorphic Measurements.
Height and weight of all subjects were measured by trained professionals. When measuring the height, all participants used the same height measuring instrument (Jiangsu Nantong Best Industrial Co., Ltd., China) to measure with an accuracy of 0.1 cm after taking off their hats and shoes. Height SDS was calculated based on normal values for Chinese children[25]. When measuring the body weight, all participants were on an empty stomach and wearing light clothes, using the same electronic scale (Guangdong Xiangshan Weighing Apparatus Co., Ltd., China), accurate to 0.1 kg. BMI is equal to weight (kg)/height (meter squared). The division of puberty stages is assessed by a specialist physician through a physical examination, which is based on the Turner stage[26]. Boys with testicular volume less than 4 mL and no pubic hair and girls with no breast development and no pubic hair were classified as prepubertal[27, 28]. Measurement of systolic blood pressure (SBP) and diastolic blood pressure (DBP) requires the patient to sit and rest for at least 5 minutes, skilled nurses use Omron HBP-1300 electronic sphygmomanometer to measure the blood pressure of the right arm three times, and the interval between each measurement is not less than 2 minutes. Then, the average of the SBP and DBP measurements was calculated and recorded.
Laboratory Measurements
Morning fasting blood samples were collected from all patients to determine laboratory parameters. Two types of GH stimulation tests are required to determine GH peak. The first trial was the levodopa excitation test. The specific methods are as follows: Participants weighing < 30 kg received oral levodopa 0.25 g, participants weighing ≥ 30 kg received oral levodopa 0.5 g, blood samples were collected at 0, 30, 60, 90 and 120 minutes and GH concentrations were determined. The second trial was the insulin hypoglycaemia test. The specific method is as follows: 0.1 U/kg insulin was injected subcutaneously, and GH levels were measured at time points of 0, 15, 30, 60, 90, and 120 min, respectively. The GH concentration was determined by a chemiluminescence method (ACCESS2, Beckman Coulter; USA) with a sensitivity of 0.010 µg/l. Serum IGF-1 concentration was determined by the chemiluminescence immunometric method (DPC IMMULITE 1000 analyser, SIEMENS, Germany), and the intra-assay and inter-assay coefficients were 3.0% and 6.2%, respectively. Renal function-related indicators including creatinine (Cr) and uric acid (UA) ,blood lipid-related indicators including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein C (LDL-c), and triglycerides (TG), with fasting blood glucose (FBG), alanine aminotransferase (ALT)were measured by an automatic biochemical analyzer (Cobas c702, Roche; Shanghai, China). The UHR was obtained as UA (mg/dl)/HDL (mg/dl).
Statistical Analysis.
All data were analyzed using the statistical packages R (http://www.R-project.org, The R Foundation) and EmpowerStats (http://www.empowerstats.com, X&Y Solutions, Inc., Boston, MA) conduct. Continuous variables that fit the normal distribution are expressed as mean ± standard deviation; if not, the median (interquartile range) is used. First, univariate analysis was used to determine the association between UHR and ALT and other independent variables. The relationship between UHR and ALT was then investigated using smooth curve fitting after adjusting for potential confounders. Finally, a multivariate piecewise linear regression model was applied to test the threshold association between UHR and ALT. P-values < 0.05 (two-sided) were considered statistically significant.