Lipid accumulation product (LAP) is associated with the presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults.
Here we evaluated the ability of LAP to predict NAFLD in obese children.
Eighty obese children (38 girls; age 6–18 years) were included. Anthropometric measurements and biochemical values were obtained from the patients’ medical records. LAP was calculated as [waist circumference (WC) (cm) – 58]×triglycerides (mmol/L) in girls; [WC (cm) – 65]×triglycerides (mmol/ L) in boys. The minLAP and adjLAP were described (3% and 50% of WC values, respectively) and the total/high-density lipoprotein cholesterol index (TC/HDL-C) was calculated. NAFLD was observed on ultrasound, and patients were divided into 3 groups by steatosis grade (normal, grade 0; mild, grade 1; moderate-severe, grade 2–3). The area under the curve (AUC) and appropriate index cutoff points were calculated by receiver operator characteristic analysis.
LAP was positively correlated with puberty stage (rho=0.409;
LAP is a powerful and easy tool to predict NAFLD in childhood. If LAP is ≥42.7, NAFLD should be suspected. This is the first study to assess LAP diagnostic accuracy for childhood obesity.
Lipid accumulation product (LAP) was first described as an alternative and powerful index for recognizing cardiovascular risk in adults [
In childhood, NAFLD is the major cause of chronic liver disease and its prevalence rises parallelly to obesity which becomes a common public health problem in the whole world. It includes a spectrum ranging from simple steatosis through nonalcoholic steatohepatitis to cirrhosis and end-stage liver disease; so early diagnosis and treatment are crucial like other comorbidities of obesity. Diagnostic procedures comprimise a combination of clinical parameters, laboratory and radiological findings. While only histology can distinguish simple steatosis or mild inflamatory changes from steatohepatosis, liver biopsy represents an invasive screening procedure [
Eighty children (38 girls) aged between 6 and 18 years, diagnosed with obesity according to body mass index (BMI) ≥ 95th percentile for sex and age were included [
Sistolic/diastolic blood pressure (BP) values and Tanner stage were obtained from the medical records [
Biochemical and hormone levels routinely obtained at admission including fasting glucose/insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TG were recorded. Glucose was analyzed using the hexokinase method. TG, TC and HDL-C, uric acid, ALT, AST were assayed using the enzymatic colorimetric method and LDL-C level was calculated using the Friedewald formula. Serum insulin was measured according to the electrochemiluminescence immunoassay method. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using the following formula: [fasting insulin (mIU/L)×fasting glucose (mg/dL)/405]. A HOMA-IR value greater than 3.16 was used to define insulin resistance [
The diagnosis of NAFLD was based on the presence of hepatic steatosis on liver ultrasonography that was not associated with acute or chronic liver diseases and the use of steatogenic medication [
We divided the patients clinically into 3 groups according to ultrasound grading as follows, normal, grade 0; mild, grade 1; moderate-severe, grades 2–3.
Descriptive statistics were presented as numbers and percentages for categorical variables, mean±standard deviation or median (interquartile range) for continuous variables depending on normal distribution. Chi-square test was used to compare ratios of sex and puberty stage according to NAFLD. To compare continuous variables according to NAFLD status, Student t test or Mann-Whitney test was used depending on parametric test assumptions. Spearman rank correlation coefficient was calculated for the relationships between LAP and puberty stage, fasting insulin, HOMA-IR, uric acid and TC/HDL-C. To determine the availability of LAP, adjLAP and minLAP variables in the diagnosis of hepatosteatosis, cutoff points were determined by receiver operating characteristic (ROC) analysis. Area under curve (AUC), cutoff point, sensitivity and specificity was calculated. To compare AUC in the ROC analysis MedCalc Version 18 (DEMO) (MedCalc Software bvba, Ostend, Belgium;
The Institutional Review Board (IRB) of the Health Science University Zeynep Kamil Maternity and Children’s Diseases Training and Research Hospital approved the study (IRB No. 139/20.10.2017) and written informed consent was attained from guardians and parents.
Anthropometric measurements, biochemical values and indexes in patients with and without liver fat are summarized in the
The LAP showed a positive and moderate correlation with puberty stage (rho=0.409;
It was found that LA
No difference between the AUC values of the 3 indexes was obtained (
The medians and
The main concerns about NAFLD are that its prevalence is rising worldwide and that it is the most common cause of chronic liver disease in childhood. The major cause of childhood NAFLD is obesity. The NAFLD should be suspected in overweight/obese children and adolescents if they consume drinks with high fructose content, if they have a strong family story and if their WC is above 95th percentile for age and sex [
The obesity and its complications such as NAFLD are important public health problems and also a source of economic burden. We consider that we need easier and less expensive methods for screening. The LAP was first introduced by Kahn [
Dai et al. [
Dai et al. [
Lee and Jeong [
We did not obtain any significant difference between the AUC values of LAP, minLAP and adjLAP. As LAP had the highest AUC value, we can easily suggest that there is no need for adjustment according to 50% and 3% of WC in patients between the ages of 6–18 years.
There are limitations to our study. First, we did not identify different cutoff values for LAP according to sex while a larger study group was needed. Secondly, as it was a retrospective study, we could not reach to B
In conclusion, LAP is an available, easy and inexpensive tool to predict NAFLD in children with obesity and it is correlated with fasting insulin, HOMA-IR, TC/HDL-C, and uric acid level. This is the first study assessing the accuracy of LAP in childhood obesity.
No potential conflict of interest relevant to this article was reported.
Receiver operating characteristic curves for the indices of nonalcoholic fatty liver disease in our study population. LAP, lipid accumulation product.
Clinical features and laboratory findings of patients with and without nonalcoholic fatty liver disease (NAFLD)
Variable | NAFLD |
Statistical analysis | ||
---|---|---|---|---|
No (n=39) | Yes (n=41) | |||
Age (yr) | 11.1±2.8 | 11.9±2.6 | 0.198 | |
Sex, n (%) | ||||
Girl (n=38) | 25 (31.3) | 13 (16.3) | ||
Boy (n=42) | 14 (17.4) | 28 (35.0) | ||
Pubertal stage, n (%) | ||||
Stage 1 (n=22) | 16 (20.0) | 6 (7.4) | ||
Stage 2 (n=22) | 5 (6.3) | 17 (21.3) | ||
Stage 3 (n=12) | 7 (8.8) | 5 (6.3) | ||
Stage 4 (n=15) | 6 (7.4) | 9 (11.2) | ||
Stage 5 (n=9) | 5 (6.3) | 4 (5.0) | ||
Weight SDS | 2.55 (0.90) | 2.99 (1.21) | ||
Height SDS | 0.73±0.96 | 0.97±1.37 | 0.374 | |
BMI | 26.9 (6.19) | 30.7 (4.43) | ||
BMI SDS | 2.38±0.48 | 2.76±0.6 | ||
BMI % | 98.7 (1.7) | 99.7 (1) | ||
WC (cm) | 89.7±13.3 | 98.8±10.5 | ||
Systolic BP (mmHg) (n=28) | 115.0 (14.3) | 122.5 (10) | ||
Diastolic BP (mmHg) (n=28) | 73±8 | 77±9 | 0.100 | |
Fasting glucose (mg/dL) | 90±8 | 89±7 | 0.452 | |
Insulin (uU/mL) | 12.7 (9.7) | 17.4 (8.25) | ||
HOMAIR | 2.93±1.5 | 4.01±1.54 | ||
ALT (IU/L) | 17 (10) | 28 (22) | ||
AST (IU/L) (n=30) | 20 (6) | 21 (9) | 0.285 | |
Uric acid (mg/dL) (n=77) | 4.7 (1.3) | 5.2 (1.5) | ||
Cholesterol (mg/dL) | 163±34 | 170±26 | 0.257 | |
Triglyceride (mg/dL) | 91 (52) | 114 (62) | 0.077 | |
HDLC (mg/dL) (n=79) | 45 (13) | 47 (16) | 0.764 | |
LDLC (mg/dL) (n=79) | 94±28 | 101.3±19.5 | 0.197 | |
TC/HDLC (n=79) | 3.74 (0.91) | 3.88 (1.41) | 0.111 | |
LAP | 30.4 (20.3) | 42.8 (43) | ||
adjLAP (%50) | 32.1 (23.9) | 43.3 (40.7) | ||
minLAP (%3) | 45.9 (23.9) | 56 (48.5) |
Values are presented as mean±standard deviation or median (interquartile range) unless otherwise indicated.
SDS, standard deviation score; BMI, body mass index; WC, waist circumference; BP, blood pressure; HOMA-IR, homeostasis model assessment of insulin resistance; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HDL-C, high-density lipoprotezin cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; LAP, lipid accumulation product.
Boldface indicates a statistically significant difference with
Correlations of adjLAP and minLAP
Variable | adjLAP |
minLAP |
||
---|---|---|---|---|
rho | rho | |||
Puberty stage | 0.282 | 0.269 | ||
Fasting insulin | 0.461 | 0.429 | ||
HOMAIR | 0.439 | 0.411 | ||
Uric acid | 0.468 | 0.449 | ||
TC/HDLC | 0.545 | 0.577 | ||
HDLC | 0.357 | 0.373 |
LAP, lipid accumulation product; HOMA-IR, homeostasis model assessment of insulin resistance; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
Boldface indicates a statistically significant difference with
Area under the curve values of the indices for nonalcoholic fatty liver disease
Variable | AUC | SE of AUC | 95% CI of AUC |
---|---|---|---|
LAP | 0.698 | 0.0591 | 0.585–0.796 |
adjLAP | 0.691 | 0.0589 | 0.578–0.789 |
minLAP | 0.673 | 0.0602 | 0.559–0.774 |
AUC, area under the curve; SE, standard error; LAP, lipid accumulation product.
Comparison of area under the curve values of the indices for nonalcoholic fatty liver disease
Variable 1 | Variable 2 | ||
---|---|---|---|
LAP | adjLAP | 0.270 | 0.787 |
LAP | minLAP | 0.890 | 0.374 |
adjLAP | minLAP | 1.805 | 0.071 |
LAP, lipid accumulation product.
Comparison of LAP indices by NAFLD severity
Variable | Normal (n=39) | Mild (n=27) | Moderate-severe (n=14) | Statistical analysisa) | |
---|---|---|---|---|---|
LAP | 30.4 (20.3)a) | 42.7 (44.9)b) | 48.1 (44.8)b) | 9.486 | |
adjLAP | 32.1 (23.9)a) | 40.9 (42.2)b) | 48.9 (39.8)a),b) | 8.775 | |
minLAP | 45.9 (23.9)a) | 53.9 (49.5)a) | 63.5 (49.3)a) | 7.277 |
LAP, lipid accumulation product; NAFLD, nonalcoholic fatty liver disease.
*
Small letters shown the differences groups: a)Normal <mild and moderate to severe, b)Normal <moderate to severe.
Boldface indicates a statistically significant difference with