Genetic risk score prediction of leg fat and insulin sensitivity differs by race/ethnicity in early pubertal children

Abstract

Summary Background In the United States, the underlying reasons for racial/ethnic disparities in type 2 diabetes risk remain unclear. However, differences in genetic risk for insulin resistance and peripheral adipose tissue distribution may be contributing factors. Objective To investigate racial/ethnic differences in associations of genetic risk for insulin resistance with leg fat and insulin sensitivity in a cohort of American children. Methods Participants were healthy European–American (n = 83), African–American (n = 79) and Hispanic–American (n = 74) children aged 7–12 years. Genetic risk scores were derived from published variants associated with insulin resistance phenotypes in European adults. Body composition was assessed using dual‐energy X‐ray absorptiometry. Insulin sensitivity was determined from the frequently sampled intravenous glucose tolerance test and minimal modelling. Statistical models were adjusted for age, sex, pubertal stage and body composition. Results In the combined cohort, risk score was inversely associated with insulin sensitivity (p = 0.033) but not leg fat (p = 0.170). Within Hispanic Americans, risk score was inversely associated with insulin sensitivity (p = 0.027) and leg fat (p = 0.005), while associations were non‐significant in European and African Americans (p > 0.200). Conclusions The higher type 2 diabetes risk observed among Hispanic Americans may have a genetic basis related to an inability to store lipid in peripheral adipose tissue.

Associations of renal sinus fat with blood pressure and ectopic fat in a diverse cohort of adults

“…Population heterogeneity in the extent to which insulin resistance is attributed to genetic vs acquired factors, and in the nature of both, undoubtedly exists. However, it is possible that the frequency within a given population (e.g., AA and EA) of genetic variation in specific loci that affect insulin sensitivity exists [ 50 ]. Future research is necessary to clarify the unique pathophysiological mechanisms underlying accumulation of ectopic fat in AA and EA populations, and ultimately how these differences influence chronic disease risk.…”

Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance

“…Ancestry is associated with variation in genes that affect metabolism, manifest as phenotypic characters, and contribute to racial and ethnic differences in risk for chronic disease. Examples of phenotypic traits that differ with ancestry include the greater acute insulin response, greater beta-cell response, and lower hepatic insulin extraction, all of which have been well documented in Black compared to White children and adults (59,60). In a clinical trial that aimed to determine if moderate carbohydrate restriction was beneficial for body composition and metabolic health among men and women with overweight or obesity, Black participants on the lower-carbohydrate diet (43,18, and 39% of energy from carbohydrate, protein, and fat, respectively) for 16 weeks lost more body fat than those on the low-fat diet (55, 18, and 27% of energy from carbohydrate, protein, and fat, respectively) (60).…”