Genetic risk scores for insulin resistance tied to cardiometabolic measures for children
Key takeaways:
- Two adult-based genetic risk scores for insulin resistance were tied to higher odds for insulin resistance in children.
- A genetic risk score specifically tailored toward children is needed.
Genetic risk scores for predicting insulin resistance that were developed for adults are also tied to some cardiometabolic metrics in children and adolescents, according to study findings.
Researchers assessed three genetic risk scores for adult insulin resistance and their associations with cardiometabolic measures in children and adolescents with and without obesity. Higher genetic risk score based on fasting insulin levels and oral glucose tolerance test were both associated with an increased likelihood for insulin resistance among children and adolescents, according to the researchers.
“Our findings highlight the need for exploratory interventions that specifically target children with obesity who have the highest risk of insulin resistance-related dysmetabolism,” Niels Grarup, MD, PhD, DMSc, precision medicine scientific director at Novo Nordisk and formerly an associate professor at the Novo Nordisk Foundation Center for Basic Metabolic Research at University of Copenhagen in Denmark, and colleagues wrote in a study published in The Journal of Clinical Endocrinology & Metabolism. “Conducting tailored clinical trials in this high-risk group could help test the feasibility and efficacy of personalized treatment strategies.”
Researchers used data from previously published studies to develop three genetic risk scores for insulin resistance, with one based on fasting insulin levels, a second based on OGTT measures and the third based on insulin-resistance related phenotypes. Data were collected from 1,680 children and adolescents with overweight or obesity and 1,804 children and adolescents without obesity who participated in the HOLBAEK study in Denmark. Insulin resistance was defined as a homeostasis model assessment of insulin resistance (HOMA-IR) measure higher than the 90th percentile based on age and sex reference values.
When both groups of participants were combined, genetic risk score based on fasting insulin was associated with higher fasting insulin (beta = 0.053; P = .0001), HOMA-IR (beta = 0.48; P = .002), C-peptide (beta = 0.058; P = .002), triglycerides (beta = 0.046; P = .002) and gamma-glutamyl transferase (beta = 0.04; P = .007). A genetic risk score based on insulin resistance-related phenotypes was associated with lower HDL cholesterol (beta = –0.054; P = .0005) and higher triglycerides (beta = 0.05; P = .0007). A genetic risk score based on OGTT was tied to lower total cholesterol and LDL cholesterol and higher alanine aminotransferase (ALT; P < .05 for all).
Children and adolescents with a higher genetic risk score for insulin resistance based on fasting insulin levels had increased odds for insulin resistance (OR = 1.2; 95% CI, 1.09-1.31) and an ALT level higher than 24.5 U/L for girls and 31.5 U/L for boys (OR = 1.13; 95% CI, 1.04-1.21). An increased genetic risk score based on OGTT results was associated with a higher likelihood for insulin resistance (OR = 1.15; 95% CI, 1.04-1.26) and liver fat of 5% or higher (OR = 1.39; 95% CI, 1.14-1.65).
Some of the study limitations included identifying insulin resistance based on fasting measures and a lack of data on environmental factors that may affect insulin resistance, according to the researchers.
“There is a need for further research to develop a pediatric-specific insulin resistance-related genetic risk score, establish appropriate risk thresholds, and evaluate the predictive power of genetic risk scores for insulin resistance and its progression over time,” the researchers wrote. “Also, future longitudinal studies are crucial for understanding genetic impacts on obesity treatment responses and help to identify risk factors for insulin resistance progression.”
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