Abstract
Purpose
To investigate the relationship between the single-point insulin sensitivity estimator (SPISE) index, an insulin sensitivity indicator validated in adolescents and adults, and metabolic profile in overweight/obese children, and to evaluate whether basal SPISE is predictive of impaired glucose regulation (IGR) development later in life.
Methods
The SPISE index (= 600 × HDL0.185/Triglycerides0.2 × BMI1.338) was calculated in 909 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy, and in 99 normal-weight, age-, sex-comparable children, selected as a reference group, together with other insulin-derived indicators of insulin sensitivity/resistance. 200 overweight/obese children were followed-up for 6.5 [3.5–10] years, data were used for longitudinal retrospective investigations.
Results
At baseline, 96/909 (11%) overweight/obese children had IGR; in this subgroup, SPISE was significantly lower than in normo-glycaemic youths (6.3 ± 1.7 vs. 7 ± 1.6, p < 0.001). The SPISE index correlated positively with the insulin sensitivity index (ISI) and the disposition index (DI), negatively with age, blood pressure, HOMA-IR, basal and 120 min blood glucose and insulin (all p values < 0.001). A correlation between SPISE, HOMA-IR and ISI was also reported in normal-weight children. At the 6.5-year follow-up, lower basal SPISE—but not ISI or HOMA-IR—was an independent predictor of IGR development (OR = 3.89(1.65–9.13), p = 0.002; AUROC: 0.82(0.72–0.92), p < 0.001).
Conclusion
In children, low SPISE index is significantly associated with metabolic abnormalities and predicts the development of IGR in life.
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Introduction
Overweight and obesity in childhood are conditions epidemically spread worldwide, and the dramatic increase of their incidence in the last decades has become a relevant public health issue around the world [1]. Data show that 17.9% of European children were overweight or obese during the period 2006–2016. The prevalence estimate of obesity was 5.3%, with highest values reported in the Southern European countries [2]. The increasing prevalence in children comes with escalations in both current childhood and future adulthood morbidity and mortality [3], but also in concomitant costs [4].
Early onset obesity is an independent risk factor for the development of insulin resistance and type 2 diabetes (T2D)[16], whereas most of the population-based health surveys include BMI and lipid profile [23], the SPISE index may also be used as a sensitive and easy method to assess insulin sensitivity at the population level.
The SPISE index has been validated in a cross-sectional investigation including a large cohort of over 1200 nondiabetic adults and 29 obese adolescents [23]. In this study, a cut-off value of SPISE below 6.61 was proposed to indicate the presence of insulin resistance, as estimated by the comparison with the clamp-derived M value.
Conversely, our study is the first investigation exploring the SPISE index in the prediction of impaired glucose regulation development in overweight and obese children. Thus, rather than using a previously identified SPISE cut-off obtained in a non-comparable population and study design, in our study we explored whether belonging to the lowest quartile of the SPISE index distribution, i.e. SPISE below 6.08, at baseline was associated with the development of altered glucose metabolism. Thus, a SPISE index cut-off < 6.08 may be proposed as a novel threshold for low insulin sensitivity in children which could predict the development of dysglycaemia later in life in the setting of the real world evidence.
The rationale of the SPISE index to identify insulin resistance is particularly intriguing: TG and HDL represent changes in lipids and lipoproteins that are among the earliest manifestations of insulin resistance [48,49,50]. Indeed, insulin resistance measured by euglycaemic clamp is associated with adverse lipid and lipoprotein changes favoring atherosclerosis even in subjects without diabetes. The addition of BMI, another easy indirect measure of adipose tissue and insulin sensitivity, further enhances the sensitivity of the SPISE index. For all these characteristics, the SPISE index, but not traditional insulin-derived indicators of insulin sensitivity/resistance such ad ISI and HOMA-IR, performed very well as a strong independent predictor of development of IGR in the large population of overweight and obese children included in this study.
In conclusion, this study demonstrates that the SPISE index is a strong indicator of insulin sensitivity in children with and without body weight excess, and that in overweight/obese individuals it predicts the development of impaired glucose regulation later in life independently from potential confounders. Finally, for its characteristics of non-invasive, low-cost and simple to estimate index, the SPISE index may represent an easy surrogate of insulin sensitivity in overweight/obese children to be used as a screening tool for metabolic risk assessment on a large scale.
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Funding
Open access funding provided by Università degli Studi dell’Aquila within the CRUI-CARE Agreement. This work was supported by Research Grants from the Department MeSVA, University of L’Aquila (Bando Ricerca FFO 2020 and FFO 2021) to Marco G. Baroni, Sapienza University of Rome “Ricerca Ateneo” to M.G.Cavallo. Ilaria Barchetta is supported by a Grant from Eli Lilly Foundation.
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Barchetta, I., Dule, S., Bertoccini, L. et al. The single-point insulin sensitivity estimator (SPISE) index is a strong predictor of abnormal glucose metabolism in overweight/obese children: a long-term follow-up study. J Endocrinol Invest 45, 43–51 (2022). https://doi.org/10.1007/s40618-021-01612-6
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DOI: https://doi.org/10.1007/s40618-021-01612-6