Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease
Dieter Furthner1,2, Christian-Heinz Anderwald2,3,4, Peter Bergsten5
1Department of Pediatrics, Salzkammergutklinikum Voecklabruck, Voecklabruck, Austria.
Insights
The single point insulin sensitivity estimator (SPISE) effectively identifies hepatic insulin resistance in pediatric non-alcoholic fatty liver disease (NAFLD). This novel index demonstrates superior performance compared to existing methods in children with obesity.
Area of Science:
- Pediatric Endocrinology
- Hepatology
- Metabolic Syndrome
Background:
- Attenuated insulin sensitivity (IS) is a key characteristic of pediatric non-alcoholic fatty liver disease (NAFLD).
- The single point insulin sensitivity estimator (SPISE) was developed using triglycerides, high-density-lipoprotein, and body-mass-index (BMI).
- SPISE has been validated against the euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents.
Purpose of the Study:
- To evaluate the performance of SPISE in estimating hepatic insulin sensitivity.
- To compare SPISE with established indices for diagnosing hepatic insulin resistance in children and adolescents.
- To introduce SPISE as a novel, inexpensive index for hepatic insulin resistance.
Main Methods:
- Ninety-nine pubertal subjects with obesity were stratified into NAFLD and non-NAFLD groups using MRI.
- Insulin sensitivity (IS) was determined using EHCT in a subgroup of 17 participants.
- Receiver-operating-characteristic (ROC) curve analysis was performed to assess the diagnostic ability of SPISE, HOMA-IR, and HIRI.
Main Results:
- SPISE was significantly lower in the NAFLD group compared to the non-NAFLD group in both males and females (P<0.05).
- In males, ROC-AUC for SPISE was 0.71 (P=0.006), outperforming HIRI (0.50) and comparable to HOMA-IR (0.68).
- In females, ROC-AUC for SPISE was 0.74 (P=0.006), outperforming HOMA-IR (0.59) and HIRI (0.68).
Conclusions:
- SPISE is significantly lower in juvenile patients with obesity-associated NAFLD.
- SPISE demonstrates superior sensitivity and specificity in indicating hepatic insulin resistance in pediatric NAFLD patients compared to established indices.
- SPISE represents a valuable, cost-effective tool for assessing hepatic insulin resistance in pediatric populations.
Background:
Attenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity.
Materials And Methods:
Ninety-nine pubertal subjects with obesity (13.5 ± 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 ± 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (≤5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5.
Results:
SPISE was lower in NAFLD (male: 4.8 ± 1.2, female: 4.5 ± 1.1) than in non-NAFLD group (male 6.0 ± 1.6, female 5.6 ± 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%).
Conclusion:
SPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR.
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