Anthropometric characteristics of the cohort
A total of 709 obese children and adolescents, 597 with NGT (246 of White European origin, 189 African American and 162 Hispanic) and 112 with IGT (53 of White European origin, 31 African American and 28 Hispanic), participated in this study (Table 1). Among the subjects with NGT, the African American participants were heavier and had a higher BMI and BMI Z-score than their counterparts of White European and Hispanic origin. Among the IGT subjects, Hispanic participants were slightly younger than other participants, while weight, BMI and BMI Z-score were similar among the three ethnic groups. In the NGT and IGT groups, pubertal status was similar between subjects of the three ethnic groups. Overall, there were more prepubertal children in the NGT group (136 of 597) compared with the IGT group (15 of 112; p=0.02, χ
2 test).
Table 1 Anthropometric data of participants
After adjusting for age, sex and ethnicity, the weight of the participants with IGT was greater than that of the participants with NGT (100.8±32.0 vs 91.2±28.1 kg, p=0.001), as were BMI (38.67±8.39 vs 36.02±7.36 kg/m2, p=0.002) and BMI Z-score (2.52±0.36 vs 2.46±0.33, p=0.004).
Plasma glucose, insulin and C-peptide responses to the OGTT
In subjects with NGT, fasting plasma glucose and insulin levels were similar in all three ethnic groups, whereas fasting C-peptide was significantly lower in African Americans (1,005±366 pmol/l) than in obese participants of White European (1,274±660 pmol/l, p<0.001) and Hispanic (1,154±468 pmol/l, p=0.04) origin (Fig. 2). Following the oral glucose load, plasma glucose levels rose in all three groups, reaching a peak level at 30 min and decreasing gradually thereafter, reaching similar levels at 180 min. After adjusting for sex, age, BMI Z-score and 2-h glucose level, the mean increment in plasma glucose at 30 min was significantly lower in African Americans than in subjects of White European origin (p<0.001). Despite lower plasma glucose levels in African Americans, the adjusted plasma insulin response was similar in all three groups. Adjusted plasma C-peptide responses (AUC for the entire OGTT) were lower in African Americans than in subjects of White European origin (p<0.001 and p=0.016 vs White European and Hispanics, respectively). In subjects with IGT, there were no statistically significant differences among the three ethnic groups in basal and stimulated glucose, insulin and C-peptide levels.
Impact of ethnicity and glucose tolerance status on indices of insulin sensitivity, secretion and clearance
As shown in Table 2, EIS, calculated as HOMA-IR or WBISI, was comparable among the three groups in subjects with NGT, even though African American subjects had a greater BMI Z-score. Despite a similar degree of insulin resistance, after adjusting for age, sex, pubertal status and BMI Z-score, indices of insulin sensitivity were still similar between the three ethnic groups while the EIR was significantly greater in African Americans than in subjects of White European and Hispanic origin (p<0.001), as was insulin clearance (p<0.001 and p=0.003 vs White European and Hispanics, respectively). In subjects with IGT, indices of EIS were similar among the three ethnic groups. The EIR was greater in African Americans than in subjects of White European origin (p=0.02). Insulin clearance was greater in the latter than in African Americans and Hispanics.
Table 2 OGTT-derived indices in obese subjects with NGT and IGT by ethnicity
Relation of EIS and EIR in the three ethnic groups
As shown in Fig. 3, obese children and adolescents from the three ethnic groups demonstrated a distinct relation of the EIR and the EIS, African Americans demonstrating a clear shift to the right compared with their counterparts of White European and Hispanic origin. Indeed, after adjustment for age, sex, pubertal status, BMI Z-score and 2-h glucose on the OGTT, the disposition index of African Americans was significantly greater (p<0.001) than in the other groups, while it was comparable between subjects of White European origin and Hispanics (p=0.59).
EIR and insulin clearance by strata of EIS
In order to adjust for the wide variation in insulin sensitivity observed in obese participants with NGT [21], we divided the subjects into tertiles of insulin sensitivity. EIS was similar among the three ethnic groups within each tertile (Table 3, Fig. 4). Fasting C-peptide was lower in African Americans than in subjects of White European origin and Hispanics in tertiles 2 and 3. Despite significantly lower plasma glucose elevations, the increments in both plasma insulin and C-peptide levels in the African American group were of similar magnitude to those seen in White Europeans and Hispanics in each tertile.
Table 3 Obese subjects with NGT according to tertiles of insulin sensitivity
EIS was similar between the three ethnic groups within each tertile of the NGT subjects (Fig. 4). Subjects with IGT had insulin sensitivity similar to the that of the most resistant subjects with NGT. In subjects with NGT, after adjustment for age, sex, ethnicity, BMI Z-score, 2-h glucose and insulin clearance, EIR was higher in African Americans than in White Europeans (p<0.001) at any given tertile of insulin sensitivity, while Hispanics had a higher EIR than subjects of White European origin (p=0.02). Importantly, the interaction between sensitivity category and ethnicity was not significant, i.e. the magnitude of difference in the EIR across tertiles of sensitivity was similar across ethnic groups. Subjects with IGT had insulin sensitivity similar to that of the most resistant tertile of the NGT group while EIR was significantly lower (p<0.001), indicating a deterioration in beta-cell function leading to IGT.
Insulin clearance decreased with decreasing insulin sensitivity, and in subjects with IGT it was similar to that in insulin-resistant subjects with NGT. After adjusting for age, sex, BMI Z-score and 2-h glucose, at any given tertile of insulin sensitivity the clearance of insulin was lower for African American participants with NGT (p<0.001 vs White Europeans and Hispanics). Hispanics had greater clearance than subjects of White European origin (p=0.002). Importantly, the magnitude of the difference in insulin clearance was similar for the three ethnic groups across tertiles of insulin sensitivity. The ethnic differences in insulin clearance disappeared in subjects with IGT.