Homeostasis model assessment is negatively associated with the clamp-derived insulin sensitivity index in adolescents

Daniela Barros, post graduate student of the Surgical Clinic Program at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP). Ribeirão Preto, SP, Brasil.

Insulin resistance has a key role in the pathogenesis of type 2 diabetes mellitus (D’ADAMO, E., et al, 2011; FLINT, A., et al, 2011) and metabolic syndrome (POYRAZOGLU, S., et al, 2014; WEISS, R., et al, 2004), which can lead to the development of coronary artery disease (POYRAZOGLU, S., et al, 2014; PINHAS-HAMIEO, O., et al, 2007). Hence, a valid, practical and accessible method of assessing insulin resistance in this age group must be developed to monitor its progression over time, to identify adolescents at risk of developing associated factors and establish strategies for preventing and mitigating the transition from normal glucose tolerance to impaired fasting glucose and type 2 diabetes mellitus.

The homeostasis model assessment (HOMA) of insulin resistance (IR) is a surrogate marker that estimates insulin resistance based on basal measurements of plasma insulin and glucose (MATTHEWS, D.R., et al, 1985). It has been widely validated and used in clinical and epidemiological studies of adult populations (BONORA, E., et al, 2000; MOURA, F.A., et al, 2014; GELONEZE, B., et al, 2006). The HOMA-IR has also been validated as a surrogate to the clamp technique as a measure of insulin resistance in adolescents (UWAIFO, G.I., et al, 2002; GUNGOR, N., et al, 2004; YECKEL, C.W., et al, 2004; SCWARTZ, B., et al, 2008; GEORGE, L., et al, 2011).

Studies, however, have not separately validated the HOMA-IR in pubertal and postpubertal adolescents. Cross-sectional and longitudinal studies have shown that a significant physiological change in insulin sensitivity occurs during the transition from late childhood throughout adolescence, with increased insulin resistance at the onset of puberty and subsequent normalization towards the end of pubertal development (MORAN, A., et al, 1999; BALL, G.D., et al, 2006).

The study The threshold value for identifying insulin resistance (HOMA-IR) in an admixed adolescent population: A hyperglycemic clamp validated study, conducted by da Silva et al, from the State University of Campinas aimed to validate the HOMA-IR as a surrogate to the hyperglycemic clamp technique to measure insulin resistance in both pubertal and postpubertal adolescents. Also, they sought to determine the HOMA- IR cutoff values for detecting insulin resistance in both pubertal stages (SILVA, C.C., et al, 2023).

Image: Pexels.

The study sample comprised 80 adolescents of both sexes (aged 10-18 years; 37 pubertal), in which IR was assessed with the HOMA-IR and the hyperglycemic clamp (SILVA, C.C., et al, 2023).

In the multivariable linear regression analysis, adjusted for sex, age and waist circumference, the HOMA-IR was independently and negatively associated with the clamp-derived insulin sensitivity index (ISI) in both pubertal and postpubertal adolescents. Bland-Altman plots showed agreement between the predicted ISI and measured clamp-derived ISI in both pubertal stages (SILVA, C.C., et al, 2023).

The HOMA-IR showed a good discriminatory power for detecting IR in pubertal in postpubertal adolescents. This study indicates that the HOMA-IR index is strongly related with the clamp-derived ISI in both pubertal stages. As far as it is known, this is the first study to explore the association between the HOMA-IR index and the clamp-derived ISI in these two pubertal stages separately. Authors found that the HOMA-IR index was negatively associated with clamp-derived insulin sensitivity, even after adjustment for waist circumference, in both pubertal and postpubertal adolescents (SILVA, C.C., et al, 2023).

Previous trials have compared the HOMA-IR index with clamp-derived measures in pediatric populations (UWAIFO, G.I., et al, 2002; GUNGOR, N., et al, 2004; YECKEL, C.W., et al, 2004; SCWARTZ, B., et al, 2008; GEORGE, L., et al, 2011), and as well as in this study, they found a significant correlation between the two methods. However, previous studies have not demonstrated whether the HOMA-IR is capable of separately estimating insulin resistance in pubertal and postpubertal adolescents like Silva et al did.

A potential limitation of the current trial is its cross-sectional design, which does not allow for inferences of causality. Another limitation is the use of the hyperglycemic clamp technique to evaluate insulin resistance (SILVA, C.C., et al, 2023).

In summary, the HOMA- IR is a low-cost approach with potential clinical and epidemiological applications and these cutoff points can improve the detection and control of metabolic diseases in pubertal and postpubertal adolescents (SILVA, C.C., et al, 2023).

References

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To read the article, access

SILVA, C.C., et al. The threshold value for identifying insulin resistance (HOMA-IR) in an admixed adolescent population: A hyperglycemic clamp validated study. Arch. Endocrinol. Metab [online]. 2023, vol. 67, no. 1, pp. 119-125. [viewed 20 March 2023]. https://doi.org/10.20945/2359-3997000000533. Available from: https://www.scielo.br/j/aem/a/XLGyny5pvvdWrqMBJVDnPHF/

External links

Archives of Endocrinology and Metabolism – AEM: https://www.scielo.br/aem

Cleliani de Cassia da Silva – Orcid: https://orcid.org/0000-0001-5503-9533