The genetic susceptibility to increased insulin sensitivity that leads to the accumulation of fat in the hip rather than waist also reduces the risk of cardiometabolic disease — diabetes, heart disease, or stroke — in children and adolescents, according to a large study in Europe.
The research, “Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents,” appeared in the International Journal of Obesity.
Most overweight children have cardiometabolic risk factors, such as insulin resistance, impaired glucose tolerance, and elevated blood pressure. Yet the number of obese children and adolescents with a cardiometabolic risk profile within the normal range may be as high as 68 percent. The explanations for this variability remain little understood.
In adults, genetic variants linked with increased insulin sensitivity and higher fat storage on the hip than on the waist are associated with increased body fat, though the cardiometabolic risk profile is improved.
Whether this is also seen in children and adolescents remains to be studied. Such assessments could help identify who is more likely to experience cardiometabolic impairments upon weight gain, the scientists said.
They addressed this gap by developing a genetic score based on single nucleotide polymorphisms — changes in one of the building blocks of DNA — linked to increased insulin sensitivity and/or decreased waist-hip fat ratio (WHR) adjusted for body mass index (BMI).
The researchers then explored whether this genetic score correlated with obesity and cardiometabolic impairments by conducting a meta-analysis combining six groups of children and adolescents (mean age 13.1 years) from Finland, Denmark, and the United Kingdom.
Among the 7,391 participants, 2,405 (33%) were prepubertal and 1,685 (23%) were overweight or obese.
First, the team found that a genetic score with 18 of the 53 variants known for decreasing insulin resistance in adults, and 23 of the 49 known for lowering the adjusted WHR in adults, correlated with increased BMI in adults, but especially in children.
Then the investigators observed that the final genetic score, which included 33 of these variants, significantly correlated with a higher degree of obesity, but with improved body fat distribution and favorable concentrations of blood lipids, including higher levels of HDL cholesterol and lower amounts of triglycerides.
The score was also associated with higher blood levels of the anti-inflammatory protein adiponectin, and had a stronger effect on insulin concentration in the overweight/obese group than in participants with normal weight, which, according to the investigators, suggests that genetic effects may be accentuated by excess weight gain.
Overall, no differences were found between girls and boys and between children and adolescents, “suggesting that genetic predisposition to increased body fat yet improved cardiometabolic profile exerts its influence already before puberty,” the researchers stated.
The results further showed that the score predicted a normal cardiometabolic profile — defined by normal glucose and lipid concentrations — in obese children and adolescents.
Also, the 10% of participants with the highest genetic predisposition — according to the genetic score — had higher BMI and adiponectin levels, as well as lower adjusted WHR and triglyceride concentration compared to the 10% with lower risk.
“This highlights the importance of a healthy lifestyle, also among lean children and adolescents, as some of these children and adolescents might be particularly susceptible to metabolic impairments upon weight gain,” the scientists said.
“Genetic predisposition to increased insulin sensitivity and relatively higher fat storage on the hip compared to the waist leads to increased [obesity] yet a favorable cardiometabolic profile in children and adolescents,” they added.