Changes in insulin resistance and cardiovascular risk during adolescence: Establishment of differential risk in males and females

Background - Developmental changes in insulin resistance and cardiovascular risk were studied in youths 11 to 19 years of age. Methods and Results - A cohort was randomly selected after blood pressure screening of Minneapolis, Minn, school children. Studies were done 3 times on this cohort and once on their siblings ( 996 observations on 507 individuals from 363 families). Insulin sensitivity was determined by euglycemic clamp. Body mass index and waist circumference increased similarly in both sexes from ages 11 to 19 years. Body fat decreased in males and increased in females ( P < 0.001). Lean body mass increased at a steeper rate in males ( P < 0.0001). Insulin resistance was lower in males at 11 years but increased steadily to 19 years ( P = 0.003); in contrast, it did not increase in females. Thus, despite being less insulin resistant at 11 years and decreasing in fatness during puberty, males became more insulin resistant than females by 19 years of age. Triglycerides increased in males and high- density lipoprotein cholesterol decreased, whereas the opposite pattern was seen in females, which resulted in higher triglycerides and lower high- density lipoprotein cholesterol in males at 19 years. No gender difference in low- density lipoprotein or total cholesterol was seen. Systolic blood pressure increased in both sexes but at a greater rate in boys ( P = 0.03). Conclusions - During the transition from late childhood through adolescence, insulin resistance in males increased in association with increased triglycerides and decreased high- density lipoprotein cholesterol, despite a concurrent reduction in body fatness, whereas the opposite occurred in females. These gender- related developmental changes in insulin resistance, which were independent from changes in fatness, total cholesterol, and low- density lipoprotein cholesterol, are consistent with an early role for insulin resistance in the increased cardiovascular risk found in males.