Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease

Abstract

BackgroundAttenuated 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 MethodsNinety-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.ResultsSPISE 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%).ConclusionSPISE 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.

A Single-Point Insulin Sensitivity Estimator (SPISE) of 5.4 is a good predictor of both metabolic syndrome and insulin resistance in adolescents with obesity

“…In a subset of the Beta-JUDO study (n=99; 13.1y, 41% females), SPISE outperformed HOMA-IR and the Hepatic Insulin Resistance Index (HIRI) in predicting non-alcoholic fatty liver disease (NAFLD). Yet, the ability of SPISE in the prediction of NAFLD was moderate-to-good, in both males (AUC=0.71) and females (AUC=0.74) ( 26 ).…”

“…Because puberty is associated with a marked decrease in insulin sensitivity, also in healthy youth ( 28 ), it seems important to determine whether puberty might interfere with the predictive ability of SPISE. Previous studies did not address this matter, despite including pre-pubertal and pubertal patients ( 22 , 26 ). After comparing the AUC using the DeLongi test, our results show that the performance of SPISE in the prediction of MetS and IR does not vary according to the Tanner stage of participants.…”

“…So far, very few studies assessed SPISE performance for abnormal glucose metabolism or IR-related cardiometabolic disorders diagnosis in younger-age people ( 22 , 25 , 26 ); the majority was conducted in adolescents with complete pubertal development. In puberty, however, considerable metabolic and hormonal change occur resulting in a marked decrease in insulin sensitivity (IS).…”

Single Point Insulin Sensitivity Estimator (SPISE) As a Prognostic Marker for Emerging Dysglycemia in Children with Overweight or Obesity

“…Furthermore, a lower SPISE index was significantly associated with T2D, abdominal obesity, and higher levels of adiponectin and C-reactive protein in adults and adolescents [ 24 , 25 ]. Furthner et al have shown that SPISE is a surrogate marker for non-alcoholic fatty liver disease in pubertal adolescents aged 10 to 18 years with a Tanner stage of 2 to 4 [ 26 ]. SPISE performed better than HOMA-IR when compared to liver MRI as a gold standard [ 26 ].…”

“…Furthner et al have shown that SPISE is a surrogate marker for non-alcoholic fatty liver disease in pubertal adolescents aged 10 to 18 years with a Tanner stage of 2 to 4 [ 26 ]. SPISE performed better than HOMA-IR when compared to liver MRI as a gold standard [ 26 ]. Barchetta recently examined the relationship between the SPISE index and various insulin sensitivity indicators in children with overweight/obesity [ 23 ].…”