The original study was approved by the Medical Ethics Committee of the Children’s Hospital of Zhejiang University School of Medicine, which was the lead centre (#2009013). Written informed consent from parents (or guardians) and children (where appropriate) were obtained, but this study involved solely the use of anonymized data. This study was conducted according to the guidelines of the Declaration of Helsinki
Participants were children and adolescents aged ≥10 but <18 years of age attending schools in 2009–2010 in eight cities across China, namely Beijing, Chongqing, Hangzhou, Lanxi, Nanning, Shanghai, Tianjin, and Xiaoshan. Exclusion criteria for this study was any pre-diagnosed chronic heart, lung, kidney, endocrine, or metabolic disease.
Participants underwent clinical assessments at their school performed by research nurses, while wearing examination gowns. Standing height was measured to the nearest mm using a stadiometer, while bare feet. Weight was measured with electronic scales to the nearest 0.1 kg, and body mass index (BMI) calculated as per standard formula. The hip circumference was measured around the fullest part of the hips with the participant standing straight with their feet together. Waist circumference was measured to the nearest mm with a tape measure around the participant’s body in the horizontal plane, at the level of the midpoint between the lowest rib and the iliac crest, on bare skin when in a state of expiration. Waist-to-hip and waist-to-height ratios were subsequently calculated.
Systolic (SBP) and diastolic (DBP) blood pressures were measured using a sphygmomanometer on the right upper arm while seated, and after a 5-minute rest. Blood pressure was measured twice, and the average of the two measurements recorded. The presence of acanthosis nigricans was diagnosed by the research nurses, as it is recognized as an important risk factor for the diagnosis of MetS.
All participants underwent blood tests on the morning of the assessment after an overnight fast, when venous blood samples were drawn. Fasting glucose and lipid profile were assessed, including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol. In addition, all participants underwent a simplified oral glucose tolerance test after receiving an oral glucose solution (3.75 g/kg), with blood samples drawn at 0 and 120 minutes.
Definition of metabolic syndrome
The International Diabetes Federation (IDF) criteria for the MetS must include central obesity, which is usually defined as waist circumference ≥90th percentile for age and sex. In China, apart from the IDF criteria, MetS is also defined based on waist-to-height ratio as it is easier to adopt in routine clinical practice without the need to refer to standardized charts. According to the 2012 guideline from the Chinese Medical Association, the MetS can be diagnosed in children and adolescents aged 10 to 18 years of age as:
1) Central obesity: waist circumference ≥90th percentile for age and sex, which is equivalent to a waist-to-height ratio ≥0.48 for boys and ≥0.46 for girls in China.
2) Any two of the following:
a) Fasting triglycerides ≥1.47 mmol/L;
b) Fasting HDL <1.03 mmol/L OR non-HDL-C ≥76 mmol/L;
c) Hypertension defined as SBP ≥130 mmHg OR DBP ≥85 mmHg;
d) Impaired fasting glucose (≥6 mmol/L) OR impaired glucose tolerance (2-hour blood glucose ≥7.8 and <11.1mmol/L) OR type 2 diabetes.
We used a combination of screening tools based on readily obtained clinical characteristics and a prediction model to identify youth with MetS using non-invasive methods. In addition, it should be noted that international guidelines discourage the diagnosis of the MetS in children younger than 10 years of age. Thus, our study population included only participants aged ≥10 years. As a result, a total of 7,330 children and adolescents with complete anthropometric and clinical data were included (Supplementary Figure S1).
A number of anthropometric, demographic, and clinical parameters were evaluated for inclusion in a prediction model, namely BMI, waist-to-hip ratio, waist-to-height ratio, age, sex, SBP, DBP, and the presence of acanthosis nigricans. Pairwise associations between continuous variables were examined to identify cases of high collinearity based on Pearson's correlation coefficients. In the event of high collinearity (|r|≥0.5), one parameter was eliminated according to its practicality in routine practice.
The model's discrimination was estimated using the area under the receiver operating characteristic curve (AUROC), as follows: poor (<0.60), possibly helpful (≥0.60 and <0.70), acceptable (≥0.70 and <0.80), excellent (≥0.80 and <0.90), and outstanding (≥0.90)[28, 29]. Model calibration (i.e. the extent to which it correctly estimates risk) was assessed as per Hosmer-Lemeshow test, with satisfactory calibration identified as p>0.05.
Selected parameters were included as predictors in a logistic regression model, where the outcome was MetS. Multiple iterations of the model were developed, with model discrimination and calibration assessed, until the most parsimonious model with the best discrimination was reached. Once the final model was developed, its accuracy and predictive capacity were assessed using the following parameters:
We have defined the threshold for MetS diagnosis at or above the 67th percentile of the probability distribution (i.e. the top tertile). Statistical analyses were performed in SPSS v25 (IBM Corp, Armonk, NY, USA) and SAS v9.4. There was no imputation of missing data.