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

Abstract

The single point insulin sensitivity estimator (SPISE) is a recently developed fasting index for insulin sensitivity based on triglycerides, high density lipoprotein cholesterol, and body mass index. SPISE has been validated in juveniles and adults; still, its role during childhood remains unclear. To evaluate the age- and sex-specific distribution of SPISE, its correlation with established fasting indexes and its application as a prognostic marker for future dysglycemia during childhood and adolescence were assessed. We performed linear modeling and correlation analyses on a cross-sectional cohort of 2107 children and adolescents (age 5 to 18.4 years) with overweight or obesity. Furthermore, survival analyses were conducted upon a longitudinal cohort of 591 children with overweight/obesity (1712 observations) with a maximum follow-up time of nearly 20 years, targeting prediabetes/dysglycemia as the end point. The SPISE index decreased significantly with age (−0.34 units per year, p < 0.001) among children and adolescents with overweight and obesity. Sex did not have an influence on SPISE. There was a modest correlation between SPISE and established fasting markers of insulin resistance (R = −0.49 for HOMA-IR, R = −0.55 for QUICKI-IR). SPISE is a better prognostic marker for future dysglycemia (hazard ratio (HR) 3.47, 95% confidence interval (CI) 1.60–7.51, p < 0.01) than HOMA-IR and QUICKI-IR (HR 2.44, 95% CI 1.24–4.81, p < 0.05). The SPISE index is a surrogate marker for insulin resistance predicting emerging dysglycemia in children with overweight or obesity, and could, therefore, be applied to pediatric cohorts that lack direct insulin assessment.

Metabolic complications of obesity in children and adolescents

“…33) In a crosssectional cohort study of 2,107 overweight or obese children and adolescents (aged 5-18.4 years), participants in the lowest versus highest quartile of SPISE values were three times more likely to develop dysglycemia during follow-up. 39) Similar findings were observed in a study of 10-17-year-olds in which the SPISE index was significantly lower in MetS than in non-MetS participants (5.5 vs. 9.4 in boys and 4.4 vs. 8.6 in girls; all P<0.001). 40) Additionally, in the International Childhood Cardiovascular Cohort Consortium (average follow-up, 22.3 years), cMetS in childhood was associated with a 2.1-fold higher risk of MetS in adulthood.…”

“…In a study of adolescents (10–18 years) using the Korea National Health and Nutrition Examination Survey (KNHANES) data, mean PsiMS was significantly higher in MetS than in non-MetS participants (3.2 vs. 1.9 in boys, 3.1 vs. 1.8 in girls; all P<0.001) [ 33 ]. In a cross-sectional cohort study of 2,107 overweight or obese children and adolescents (aged 5–18.4 years), participants in the lowest versus highest quartile of SPISE values were three times more likely to develop dysglycemia during follow-up [ 39 ]. Similar findings were observed in a study of 10–17-year-olds in which the SPISE index was significantly lower in MetS than in non-MetS participants (5.5 vs. 9.4 in boys and 4.4 vs. 8.6 in girls; all P<0.001) [ 40 ].…”

“…The global prevalence of NAFLD is 4.2%–9.6% and can reach 38% in pediatric obese populations [ 43 ]. In a study of overweight and obese children aged 5–15 years, those with an ultrasound-diagnosed fatty liver had significantly higher FLI values than those without a fatty liver (odds ratio, 3.5; 95% CI, 1.1–11.3) [ 39 ]. These indicators provide valuable insight into the metabolic complications associated with childhood obesity and aid in the early identification and intervention to prevent long-term health consequences.…”

Are there relevant thresholds of insulin-independent indices across the lifespan to predict alterations in glycemic control?—Authors’ reply

“…It has been validated in adults and adolescents in relation to the clamp method 8 and serves as a surrogate marker for nonalcoholic fatty liver disease, type 2 diabetes and abdominal obesity. 9 , 10 , 11 , 12 Cut-off values covering childhood to old age are lacking for both TyG and SPISE index.…”

“…Of note, in a previous analysis of children with obesity, comparing the highest vs. the lowest quartile of SPISE index resulted in better prediction of emerging dysglycemia than using HOMA-IR. 12 Thus, SPISE index conveys useful information regarding glucose-insulin-metabolism in general, but detecting a specific cut-off point appears to be difficult.…”