The Role of European Genetic Admixture in the Etiology of the Insulin Resistance Syndrome in Children: Are the Effects Mediated by Fat Accumulation?

Abstract

Objective To evaluate the contribution of European genetic admixture (EUADM) to the insulin resistance syndrome (IRS) in a multi-ethnic sample of children aged 7–12 years and if body fat affects this relationship. Study design Anthropometric measurements and blood pressure were assessed in 243 children. After an overnight fast, an intravenous glucose tolerance test was conducted, and measures of fasting insulin/glucose, lipids, insulin sensitivity (SI), and acute insulin response to glucose (AIRg) were obtained. The proportion of EUADM was determined by maximum likelihood estimation using 140 ancestry informative markers. Participants were stratified into tertiles according to the proportion of EUADM for analyses. Subjects were categorized as lean or obese using percent fat cut-points (25% in boys, 30% in girls). Results Among lean subjects (72%), the tertile representing the greatest proportion of EUADM was associated with higher SI (p<0.001) and glucose (p<0.05) and lower insulin (p<0.05), AIRg (p<0.001), HDL-C (p=0.05), and blood pressure (p<0.05). However, among obese subjects, EUADM was associated with only SI (p<0.05). Conclusion Our results suggest that population differences in the IRS likely have a genetic component. However, the influences of genetic background may be masked by obesity.

Race, Childhood Insulin, Childhood Caloric Intake, and Class 3 Obesity at Age 24: 14‐Year Prospective Study of Schoolgirls

“…How do race and insulin affect obesity risk, and what are the physiologic differences between whites and blacks that create the obesogenic metabolic condition? Higher insulin resistance, higher insulin throughout the BMI distribution, and differences in insulin secretion dynamics appear to be major physiologic difference between blacks and whites (19,35,36,37,38), increasing risk of obesity and T2DM in blacks. Moreover, black girls have higher caloric intake than white girls during adolescence (11,19), despite under‐reporting of energy intake (39).…”

Genetic Admixture and Obesity: Recent Perspectives and Future Applications

“…Estimates of genetic admixture have also been used to evaluate the contributions or the mediation of ancestral background in physiological aspects known to mediate fat accumulation, including insulin sensitivity [10,11,34,35], physical activity and fitness [31,36], dietary factors [37], and IGF-1 [38]. While these studies provide insight into the possible applications of genetic admixture to the complex nature of fat accumulation, much work is still needed to identify the potential mechanistic role of ancestral genetics in obesity-related traits.…”

Influence of LRP5 (rs556442) polymorphism on insulin resistance in healthy Iranian children and adolescents

“…Insulin resistance is linked to the pathophysiologic pathways that originate during childhood. Conversely, an individual's genetic background variation may possibly cause alterations in these pathways, which leads to disease progression (23). In addition to genetic factors, metabolic factors such as obesity and abdominal fat deposition impact insulin resistance (13).…”