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African-American (AA) children are hyperinsulinemic and insulin resistant compared with American White (AW) children. This study investigated 1) whether AA/AW differences in insulinemia are associated with differences in insulin clearance; 2) whether dietary patterns, mainly carbohydrate and fat intake, play a role; and 3) whether the quantitative relationship between insulin sensitivity and secretion is similar between AA and AW children. Forty-four prepubertal children (22 AA and 22 AW) with comparable body composition and visceral adiposity were studied. All underwent a 3-h hyperinsulinemic (40 mU ⅐ m ؊2 ⅐ min ؊1)-euglycemic clamp to calculate insulin sensitivity and insulin clearance and a 2-h hyperglycemic clamp (12.5 mmol/l) to assess first-and second-phase insulin responses. Twenty-four-hour food recalls were analyzed for macronutrient intake. Insulin clearance (19.5 ؎ 0.7 vs. 22.9 ؎ 1.1 ml ⅐ min ؊1 ⅐ kg ؊1 fat-free mass [FFM]; P ‫؍‬ 0.011) and insulin sensitivity were lower in AA versus AW children (14.8 ؎ 1.0 vs. 18.9 ؎ 1.4 mol ⅐ min ؊1 ⅐ kg ؊1 FFM; P ‫؍‬ 0.021). Both insulin clearance and insulin sensitivity correlated inversely with dietary fat/carbohydrate ratio, which was higher in AA than in white children. Fasting C-peptide and insulin were higher in AA children with no difference in proinsulin levels. First-and second-phase insulin concentrations and glucose disposition index (insulin sensitivity ؋ first-phase insulin) were higher in AA than in white children (12.8 ؎ 2.1 vs. 7.2 ؎ 0.6 mol ⅐ min ؊1 ⅐ kg ؊1 FFM; P ‫؍‬ 0.019). In conclusion, the hyperinsulinemia observed in AA children is due to both lower insulin clearance and higher insulin secretion compared with their white peers. The quantitative relationship between insulin secretion and sensitivity is upregulated in AA children. This suggests that increased insulin secretion in AA children is not merely a compensatory response to lower insulin sensitivity. Dietary factors may have a role. Additional studies are needed to determine whether metabolic/nutritional factors, possibly mediated through free fatty acids, may play a role in the hyperinsulinism observed in AA children. Diabetes 51:3014 -3019, 2002

The incidence of type 2 diabetes mellitus in children is increasing with the increasing prevalence of obesity, particularly in African-American children. We hypothesized that African-American obese adolescents are more insulin resistant than their white peers, but have lower insulin secretion, thus increasing their risk of type 2 diabetes mellitus. The present study investigated insulin sensitivity and secretion, visceral adiposity (VAT), and cardiovascular disease (CVD) risk profile in black obese adolescents (BOA) vs. white obese adolescents (WOA). Twenty-four BOA and 26 WOA underwent a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity, a hyperglycemic clamp to determine insulin secretion, dual energy x-ray absorptiometry for body composition and computed tomography scan at L4-L5 to measure VAT and sc abdominal adipose tissue. Fasting lipid and automated blood pressure measurements were obtained. The WOA and BOA groups were divided into low VAT and high VAT groups. BOA compared with WOA of similar body mass index and percent body fat had less visceral adiposity, lower hepatic glucose production, and lower lipid levels. Visceral adiposity was associated with lower insulin sensitivity in both groups [low vs. high VAT; BOA, 2.9 +/- 0.4 vs. 1.7 +/- 0.2 micromol/kg x min per pmol/liter (P = 0.016); WOA, 2.6 +/- 0.5 vs. 1.5 +/- 0.1 (P = 0.032)]. However, this was compensated by higher insulin secretion in whites (low VAT, 934.8 +/- 121.8; high VAT, 1590.6 +/- 232.8 pmol/liter; P = 0.037), but not in blacks (low VAT, 1398.9 +/- 214.0; high VAT, 1423.7 +/- 108.7 pmol/liter). Glucose disposition index (insulin sensitivity x first phase insulin) was lower in high VAT vs. low VAT BOA, but not in WOA. In each racial group, high VAT groups had elevation of systolic and diastolic blood pressure, but dyslipidemia was worse in WOA with high VAT. In conclusion, a given level of body mass index confers different metabolic risks for WOA vs. BOA. Although differences in fat patterning may help explain the more atherogenic risk profile in whites, the cause of the more diabetogenic insulin sensitivity/secretion profile in blacks remains unknown and needs to be investigated further.

OBJECTIVE -Adiponectin is an adipose tissue protein that enhances insulin sensitivity and has antiatherogenic properties. The present study investigated the relationship of adiponectin levels in adolescents to 1) obesity and body fat distribution and 2) insulin sensitivity and the components of syndrome X.RESEARCH DESIGN AND METHODS -Twenty-three normal-weight and 26 obese adolescents had fasting adiponectin, lipid profile, and proinsulin measurements performed. Hepatic and peripheral insulin sensitivity were assessed with constant-rate [6,6-2 H 2 ]glucose infusion and a 3-h hyperinsulinemic-euglycemic clamp, respectively. Body composition was evaluated by dual-energy X-ray absorptiometry, and visceral adipose tissue (VAT) and subcutaneous adipose tissue were measured by computed tomography scan at the L 4 -L 5 level.RESULTS -Obese adolescents had ϳ50% lower adiponectin than normal-weight adolescents. Moreover, obese adolescents with high (111.8 Ϯ 9.3 cm 2 ) versus low (55.4 Ϯ 2.1 cm 2 ) VAT had lower adiponectin levels (6.2 Ϯ 0.9 vs. 9.0 Ϯ 1.0 g/ml, P ϭ 0.05). Plasma adiponectin correlated positively with peripheral and hepatic insulin sensitivity (r ϭ 0.67, P Ͻ 0.001 and r ϭ 0.54, P Ͻ 0.001, respectively) and HDL (r ϭ 0.52, P Ͻ 0.001) and negatively with fasting proinsulin and the proinsulin-to-insulin ratio (r ϭ Ϫ0.64, P Ͻ 0.001 and r ϭ Ϫ0.43, P ϭ 0.003, respectively). In a multiple regression analysis, adiponectin, independently and together with BMI, explained 73% (R 2 ϭ 0.73, P Ͻ 0.001) of the variance in insulin sensitivity. Adiponectin, but not adiposity, was the significant independent determinant of the proinsulin-to-insulin ratio (R 2 ϭ 0.18, P ϭ 0.008) and of HDL (R 2 ϭ 0.45, P Ͻ 0.001).CONCLUSIONS -In summary, hypoadiponectinemia in youth is a strong and independent correlate of insulin resistance, ␤-cell dysfunction, visceral adiposity, and syndrome X. The antidiabetogenic and antiatherogenic properties of adiponectin are evident early in life and compromised in youth-onset obesity.