Table 1 presents a comparison of the clinical characteristic of the participants with or without IR and NAFLD. Obesity indicators including BMI, BMI SDS, WC, and WHtR and serum level of total cholesterol, LDL, non-HDL, triglycerides, glucose, insulin, HOMA-IR, AST, and ALT and proportion of participants with hyperuricemia were higher in the IR and NAFLD groups compared to those in the non-IR and non- NAFLD groups, respectively (total cholesterol and glucose in NAFLD/non-NAFLD, p = 0.002 and p = 0.011, respectively; for other comparisons, p < 0.001). In contrast, HDL level was lower in in the IR and NAFLD groups compared to those in the non-IR and non-NAFLD groups (all p < 0.001). Overall, the IR and NAFLD groups had higher values of Uacid and Uacid related markers than those in the non-IR and non-NAFLD groups (all p < 0.001).
Table 1
Baseline characteristics of participants with respect to IR and NAFLD
Variables | Total (n = 1,648) | IR (n = 381) | non-IR (n = 1,267) | *p value | NAFLD (n = 251) | non-NAFLD (n = 1,397) | *p value |
Age, year | 14.13 (0.07) | 13.78 (0.17) | 14.23 (0.08) | 0.018 | 14.61 (0.19) | 14.05 (0.08) | 0.008 |
Sex, female, % | 47.28 (1.36) | 36.12 (2.78) | 50.54 (1.55) | < 0.001 | 26.19 (3.06) | 51.00 (1.47) | < 0.001 |
Height SDS | 0.35 (0.03) | 0.58 (0.06) | 0.28 (0.04) | < 0.001 | 0.47 (0.10) | 0.33 (0.04) | 0.182 |
Weight SDS | 0.31 (0.04) | 1.55 (0.08) | -0.05 (0.04) | < 0.001 | 1.49 (0.10) | 0.10 (0.04) | < 0.001 |
BMI, kg/m2 | 21.39(0.15) | 25.89(0.38) | 20.60(0.14) | < 0.001 | 20.17(0.11) | 25.57(0.34) | < 0.001 |
BMI SDS | 0.18 (0.05) | 1.60 (0.10) | -0.24 (0.04) | < 0.001 | 1.57 (0.12) | -0.07 (0.05) | < 0.001 |
BMI percentile, | | | | < 0.001 | | | < 0.001 |
Normal, % | 74.48 (1.47) | 33.77 (3.12) | 86.37 (1.06) | | 35.74 (3.56) | 81.30 (1.33) | |
Overweight, % | 9.25 (0.79) | 17.41 (2.13) | 6.86 (0.79) | | 14.48 (2.46) | 8.33 (0.76) | |
Obesity, % | 16.27 (1.24) | 48.82 (3.25) | 6.77 (0.80) | | 49.78 (3.77) | 10.37 (1.11) | |
WC, cm | 72.26 (0.39) | 83.26 (0.86) | 69.04 (0.31) | < 0.001 | 84.99 (0.93) | 70.02 (0.35) | < 0.001 |
Central obesity, % | 22.14 (1.35) | 62.25 (3.15) | 10.42 (0.93) | < 0.001 | 60.15 (3.67) | 15.45 (1.22) | < 0.001 |
WHtR | 0.45 (0.00) | 0.51 (0.00) | 0.43 (0.00) | < 0.001 | 0.51 (0.01) | 0.43 (0.00) | < 0.001 |
Total cholesterol, mg/dL | 163.69 (0.86) | 170.04 (1.74) | 161.83 (0.91) | < 0.001 | 170.71 (2.51) | 162.45 (0.89) | 0.002 |
LDL, mg/dL | 94.86 (0.74) | 101.08 (1.61) | 93.05 (0.77) | < 0.001 | 103.03 (2.12) | 93.43 (0.76) | < 0.001 |
HDL, mg/dL | 51.95 (0.32) | 46.88 (0.60) | 53.43 (0.34) | < 0.001 | 47.44 (0.66) | 52.74 (0.35) | < 0.001 |
non-HDL, mg/dL | 111.74 (0.83) | 123.16 (1.68) | 108.41 (0.83) | < 0.001 | 123.26 (2.33) | 109.71 (0.84) | < 0.001 |
Cr, mg/dL | 0.67 (0.00) | 0.66 (0.01) | 0.67 (0.01) | 0.280 | 0.71 (0.01) | 0.66 (0.01) | < 0.001 |
Triglycerides, mg/dL | 87.77 (1.60) | 120.50 (3.83) | 78.21 (1.40) | < 0.001 | 109.63 (4.46) | 83.93 (1.59) | < 0.001 |
Glucose, mg/dL | 92.09 (0.22) | 96.26 (0.45) | 90.87 (0.23) | < 0.001 | 93.43 (0.57) | 91.85 (0.24) | 0.011 |
Insulin, µIU/mL | 15.37 (0.39) | 31.05 (1.21) | 10.79 (0.14) | < 0.001 | 25.00 (1.59) | 13.68 (0.31) | < 0.001 |
HOMA-IR | 3.57 (0.10) | 7.42 (0.31) | 2.44 (0.03) | < 0.001 | 5.88 (0.39) | 3.16 (0.08) | < 0.001 |
IR†, % | 22.61 (1.35) | | | | 51.14 (3.57) | 17.59 (1.31) | < 0.001 |
AST, mg/dL | 21.53 (0.30) | 24.47 (0.73) | 20.68 (0.30) | < 0.001 | 34.03 (1.38) | 19.33 (0.17) | < 0.001 |
ALT, mg/dL | 17.93 (0.51) | 28.96 (1.58) | 14.71 (0.37) | < 0.001 | 48.39 (2.08) | 12.56 (0.15) | < 0.001 |
NAFLD, % | 14.97 (1.05) | 33.86 (2.70) | 9.45 (0.98) | < 0.001 | | | |
Uacid, mg/dL | 5.49 (0.05) | 6.15 (0.09) | 5.30 (0.05) | < 0.001 | 6.56 (0.11) | 5.30 (0.04) | < 0.001 |
Hyperuricemia, % | 14.79 (1.18) | 33.48 (2.89) | 9.35 (1.06) | < 0.001 | 35.15 (3.65) | 11.21 (1.15) | < 0.001 |
Uacid/Cr | 8.43 (0.07) | 9.63 (0.15) | 8.08 (0.07) | < 0.001 | 9.54 (0.16) | 8.24 (0.07) | < 0.001 |
Uacid/HDL | 0.11 (0.00) | 0.14 (0.00) | 0.10 (0.00) | < 0.001 | 0.14 (0.00) | 0.11 (0.00) | < 0.001 |
Uacid-BMI | 120.45 (1.73) | 161.27 (4.34) | 108.58 (1.36) | < 0.001 | 173.17 (4.31) | 111.18 (1.57) | < 0.001 |
Uacid-BMI SDS | 1.81 (0.32) | 10.84 (0.78) | -0.82 (0.21) | < 0.001 | 11.17 (0.84) | 0.16 (0.29) | < 0.001 |
Uacid-WC | 405.74 (5.30) | 523.72 (12.75) | 371.41 (4.52) | < 0.001 | 567.27 (12.99) | 377.32 (4.83) | < 0.001 |
Uacid-WHtR | 2.48 (0.03) | 3.18 (0.07) | 2.28 (0.02) | < 0.001 | 3.40 (0.07) | 2.32 (0.03) | < 0.001 |
Note: Values are presented as mean (standard error), and categorical data as percentages (standard error). |
*P value is assessed using Student’s t-test and Rao-scott-Chi-square test. |
†IR was defined as the HOMA-IR of above the 95th percentile for each gender and age using Korean HOMA-IR reference data. |
Abbreviations: IR, insulin resistance; NAFLD, non-alcoholic fatty liver disease; SDS, standard deviation score; BMI, body mass index; WC, waist circumference; 90p, 90th percentile; WHtR, waist-to-height ratio; TC, total cholesterol; LDL, low-density lipoprotein cholesterol; HDL, high-density lipoprotein cholesterol; Cr, creatinine; HOMA-IR, homeostasis model assessment of insulin resistance; AST, aspartate aminotransferase; ALT, alanine aminotransferase; Uacid, uric acid.
In logistic regression analyses with IR and NAFLD as dependent variables, ORs of generalized and abdominal obesity for IR were 4.38 (95% CI, 2.23–8.63; p < 0.001) and 3.16 (95% CI, 1.70–5.86; p < 0.001), and the corresponding values for NAFLD were 4.00 (95% CI, 2.01–7.94; p < 0.01) and 1.75 (95% CI, 0.95–3.22; p 0.073), respectively (Table 2). The hyperuricemia group had OR value of 1.91 (95% CI, 1.33–2.76; p < 0.01) for IR and 1.81 (95% CI, 1.04–3.17; p 0.037) for NAFLD. In addition, OR of IR for NAFLD was 1.63 (95% CI, 1.13–2.34; p = 0.009)
Table 2
Odds ratio of IR and NAFLD according to each parameter
| IR | NAFLD |
| OR (95% Cl) | p value* | OR (95% Cl) | p value* |
BMI percentile | | | | |
Normal | Reference | | Reference | |
Overweight | 2.90 (1.69–4.97) | 0.13 | 2.17 (1.20–3.89) | 0.729 |
Obesity | 4.38 (2.23–8.63) | < 0.001 | 4.00 (2.01–7.94) | < 0.001 |
Central Obesity | 3.16 (1.70–5.86) | < 0.001 | 1.75 (0.95–3.22) | 0.073 |
Hyperuricemia | 1.91 (1.33–2.76) | < 0.001 | 1.81 (1.04–3.17) | 0.037 |
IR | | | 1.63 (1.13–2.34) | 0.009 |
NAFLD | 1.65 (1.15–2.36) | 0.006 | | |
Note: Logistic regression analyses were performed with IR and NAFLD as dependent variables. |
Abbreviations: IR, insulin resistance; NAFLD, non-alcoholic fatty liver disease; OR, odds ratio; CI, confidence interval.. |
The ORs and 95% CIs for IR and NAFLD progressively increased across tertiles of each variable including Uacid, Uacid-Cr, Uacid-HDL, Uacid-BMI, Uacid-BMI SDS, Uacid-WC, Uacid-WHtR, total cholesterol, triglycerides, LDL, non-HDL among the total subjects (Table 3). Uacid combined with obesity indices exhibited ORs of tertile 3 ranging as 8.17–18.74 compared with those of tertile 1, while the Uacid, Uacid-Cr, and Uacid-HDL exhibited ORs of tertile 3 as 4.39. 4.94, and 5.23 compared with those of tertile 1 for IR in all individuals. For NAFLD, Uacid combined with obesity indices exhibited ORs of tertile 3 ranging as 11.73–19.22 compared with those of tertile 1, while the Uacid, Uacid/Cr, and Uacid/HDL exhibited ORs of tertile 3 as 9.86, 3.83, and 6.95 compared with those of tertile 1 in all individuals. Among the indices, Uacid-BMI SDS presented the highest ORs and 95% CIs for IR in the total subjects (OR, 18.74), and Uacid-WHtR for NAFLD (OR, 19.22), respectively. Overall, the Uacid combined with obesity indices presented higher ORs and 95% CIs than the Uacid alone, Uacid/Cr, Uacid/HDL, lipid parameters for IR and the Uacid alone, Uacid/Cr, Uacid/HDL, lipid profiles, insulin, and HOMA-IR for NAFLD.
Table 3
Odds ratio for IR and NAFLD according to tertiles of each parameter
| IR | NAFLD |
| OR (95% Cl) | p value* | OR (95% Cl) | p value* |
Uacid, mg/dL | | | | |
T2 | 1.46 (1.00-2.13) | 0.013 | 3.31 (1.94–5.67) | 0.787 |
T3 | 4.39 (3.04–6.35) | < 0.001 | 9.86 (6.24–15.60) | < 0.001 |
Uacid/Cr | | | | |
T2 | 2.04 (1.40–2.95) | 0.564 | 1.73 (1.11–2.69) | 0.474 |
T3 | 4.94 (3.37–7.25) | < 0.001 | 3.83 (2.50–5.88) | < 0.001 |
Uacid/HDL | | | | |
T2 | 1.52 (1.04–2.20) | 0.007 | 1.65 (1.03–2.67) | 0.015 |
T3 | 5.23 (3.62–7.55) | < 0.001 | 6.95 (4.64–10.42) | < 0.001 |
Uacid-BMI | | | | |
T2 | 2.37 (1.56–3.62) | 0.153 | 2.40 (1.36–4.24) | 0.040 |
T3 | 8.91 (5.94–13.37) | < 0.001 | 13.64 (8.32–22.34) | < 0.001 |
Uacid-BMI SDS | | | | |
T2 | 2.59 (1.59–4.20) | 0.004 | 1.87 (1.05–3.33) | 0.005 |
T3 | 18.74 (11.44–30.69) | < 0.001 | 11.73 (7.13–19.30) | < 0.001 |
Uacid-WC | | | | |
T2 | 2.66 (1.75–4.04) | 0.635 | 3.39 (1.88–6.11) | 0.500 |
T3 | 8.17 (5.44–12.26) | < 0.001 | 15.11 (8.83–25.87) | < 0.001 |
Uacid-WHtR | | | | |
T2 | 2.54 (1.67–3.87) | 0.167 | 4.59 (2.55–8.26) | 0.824 |
T3 | 9.89 (6.54–14.95) | < 0.001 | 19.22 (11.43–32.31) | < 0.001 |
Total cholesterol, mg/dL | | | | |
T2 | 1.43 (1.03–1.99) | 0.867 | 1.07 (0.70–1.65) | 0.184 |
T3 | 1.95 (1.43–2.67) | < 0.001 | 1.86 (1.19–2.91) | 0.002 |
Triglycerides, mg/dL | | | | |
T2 | 2.34 (1.56–3.52) | 0.552 | 1.50 (0.96–2.35) | 0.445 |
T3 | 6.59 (4.50–9.65) | < 0.001 | 2.93 (1.87–4.58) | < 0.001 |
HDL, mg/dL | | | | |
T2 | 0.39 (0.28–0.53) | 0.189 | 0.41 (0.28–0.59) | 0.096 |
T3 | 0.22 (0.16–0.31) | < 0.001 | 0.30 (0.20–0.45) | < 0.001 |
LDL, mg/dL | | | | |
T2 | 1.37 (0.99–1.90) | 0.527 | 1.76 (1.14–2.72) | 0.683 |
T3 | 2.23 (1.60–3.10) | < 0.001 | 2.67 (1.73–4.13) | < 0.001 |
non-HDL, mg/dL | | | | |
T2 | 1.63 (1.15–2.30) | 0.399 | 2.31 (1.48–3.58) | 0.349 |
T3 | 3.38 (2.42–4.72) | < 0.001 | 3.82 (2.42–6.04) | < 0.001 |
Insulin, µIU/mL | | | | |
T2 | | | 2.18 (1.35–3.53) | 0.254 |
T3 | | | 7.29 (4.72–11.26) | < 0.001 |
HOMA-IR | | | | |
T2 | | | 2.42 (1.45–4.05) | 0.679 |
T3 | | | 6.97 (4.49–10.82) | < 0.001 |
Note: ORs and 95% CIs of tertiles 2 and 3 for each parameter were calculated and compared with tertile 1 as a reference. |
*p value is assessed using logistic regression. |
Abbreviations: IR, insulin resistance; NAFLD, non-alcoholic fatty liver disease; OR, odds ratio; CI, confidence interval; T, Tertitle; Uacid, uric acid; Cr, creatinine; HDL, high-density lipoprotein cholesterol; BMI, body mass index; WC, waist circumference; WHtR, waist-to-height ratio; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance |
Table 4 and Fig. 2 summarize the results of ROC curve analyses and AUCs with the corresponding 95% CIs for Uacid and Uacid related markers to predict IR and NAFLD. All variables predicted IR and NAFLD significantly (all p = 0.001). The cut-off values for IR prediction were 5.95, 9.13, 0.11, 139.89, 3.54, 438.38, and 2.56 for Uacid, Uacid-Cr, Uacid-HDL, Uacid-BMI, Uacid-BMI SDS, Uacid-WC, Uacid-WHtR, respectively. All Uacid combined with obesity indices showed higher AUC compared to Uacid, Uacid/Cr, Uacid/HDL for IR. Uacid-BMI SDS showed the largest AUC for IR detection with 0.837. In addition, Uacid/HDL presented higher AUC compared to Uacid. The cutoff values for NAFLD prediction were 5.55, 9.17, 0.12, 137.88, 3.76, 421.86, 2.49, 15.45, and 3.04 for Uacid, Uacid/Cr, Uacid/HDL, Uacid-BMI, Uacid-BMI SDS, Uacid-WC, Uacid-WHtR, insulin, and HOMA-IR, respectively. All Uacid combined with obesity indices showed higher AUC compared to Uacid, Uacid/Cr, Uacid/HDL, insulin, and HOMA-IR for NAFLD. Uacid-WHtR showed the largest AUC for NAFLD detection with 0.803. Uacid-BMI SDS presented significantly higher AUC values and 95% CIs than all other parameters for IR prediction (all p < 0.001) (Supplementary Table S1). For NAFLD prediction, all Uacid combined with obesity indices presented higher AUC compared to Uacid, Uacid/Cr, Uacid/HDL, insulin, and HOMA-IR. In addition, Uacid-BMI and Uacid- WHtR had highest AUC among the parameters.
Table 4
Cutoff values and areas under the receiver operating characteristic curves for each parameter for predicting IR and NAFLD
| IR | NAFLD |
Variables | Cutoff | Sensitivity | Specificity | AUC (95% CI) | p-value | Cutoff | Sensitivity | Specificity | AUC (95% CI) | p-value |
Uacid, mg/dL | 5.95 | 53.56 (48.54–58.58) | 73.95 (71.54–76.37) | 0.67 (0.63–0.70) | < 0.001 | 5.55 | 73.60 (68.14–79.06) | 62.03 (59.49–64.58) | 0.73 (0.70–0.77) | < 0.001 |
Uacid/Cr | 9.13 | 57.78 (52.81–62.76) | 71.59 (69.10-74.07) | 0.69 (0.66–0.72) | < 0.001 | 9.17 | 56.00 (49.85–62.15) | 69.13 (66.70-71.55) | 0.66 (0.63–0.70) | < 0.001 |
Uacid/HDL | 0.11 | 72.03 (67.51–76.55) | 63.30 (60.65–65.95) | 0.71 (0.68–0.74) | < 0.001 | 0.12 | 65.60 (59.71–71.49) | 72.85 (70.52–75.18) | 0.74 (0.71–0.77) | < 0.001 |
Uacid-BMI | 139.89 | 56.20 (51.21–61.20) | 83.50 (81.46–85.55) | 0.76 (0.73–0.79) | < 0.001 | 137.88 | 68.80 (63.06–74.54) | 80.87 (78.81–82.94) | 0.80 (0.76–0.83) | < 0.001 |
Uacid-BMI SDS | 3.54 | 74.67 (70.29–79.05) | 78.77 (76.52–81.02) | 0.84 (0.81–0.86) | < 0.001 | 3.76 | 73.20 (67.71–78.69) | 75.00 (72.73–77.27) | 0.79 (0.76–0.83) | < 0.001 |
Uacid-WC | 438.38 | 60.16 (55.23–65.09) | 75.77 (73.41–78.13) | 0.74 (0.71–0.77) | < 0.001 | 421.86 | 74.40 (68.99–79.81) | 70.70 (68.31–73.09) | 0.79 (0.76–0.82) | < 0.001 |
Uacid-WHtR | 2.56 | 67.81 (63.11–72.51) | 71.59 (69.10-74.07) | 0.76 (0.73–0.79) | < 0.001 | 2.49 | 80.40 (75.48–85.32) | 66.55 (64.07–69.02) | 0.80 (0.77–0.83) | < 0.001 |
Insulin, µIU/mL | | | | | | 15.45 | 66.53 (60.70-72.37) | 70.08 (67.68–72.48) | 0.74 (0.70–0.77) | < 0.001 |
HOMA-IR | | | | | | 3.04 | 75.30 (69.96–80.63) | 60.84 (58.29–63.40) | 0.73 (0.70–0.77) | < 0.001 |
Abbreviations: IR, insulin resistance; NAFLD, non-alcoholic fatty liver disease; AUC, area under the curve; CI, confidence interval; Uacid, uric acid; Cr, creatinine; BMI, body mass index; WC, waist circumference; WHtR, waist-to-height ratio; HOMA-IR, homeostasis model assessment of insulin resistance |