Hemoglobin A1c above threshold level is associated with decreased ß-cell function in overweight Latino youth.

OBJECTIVE: To examine whether a hemoglobin A1c (HbA1c)-identified prediabetic state (HbA1c ≥ 6.0%-6.4%) is associated with decreased insulin sensitivity (SI) and ß-cell dysfunction, known factors in the pathogenesis of type 2 diabetes, in an overweight pediatric population. STUDY DESIGN: A total of 206 healthy overweight Latino adolescents (124 males and 82 females; mean age, 13.1 ± 2.0 years) were divided into 2 groups: lower risk (n=179), with HbA1c <6.0%, and higher risk (n=27), with HbA1c 6.0%-6.4%. Measurements included HbA1c, oral glucose tolerance testing, fasting and 2-hour glucose and insulin, SI, acute insulin response, and disposition index (an index of ß-cell function) by the frequently sampled intravenous glucose tolerance test with minimal modeling. Body fat was determined by dual-energy X-ray absorptiometry. RESULTS: Compared with the lower risk group, the higher risk group had 21% lower SI (1.21 ± 0.06 vs 1.54 ± 0.13; P<.05), 30% lower acute insulin response (928 ± 102 vs 1342 ± 56; P<.01), and a 31% lower disposition index (1390 ± 146 vs 2023 ± 83; P=.001) after adjusting for age and total percent body fat. CONCLUSION: These data provide clear evidence of greater impairment of ß-cell function in overweight Latino children with HbA1c 6.0%-6.4%, and thereby support the adoption of the International Expert Committee's HbA1c-determined definition of high-risk state for overweight children at risk for type 2 diabetes.

Subclinical atherosclerosis in Latino youth: progression of carotid intima-media thickness and its relationship to cardiometabolic risk factors.

OBJECTIVE: To assess carotid artery intima-media thickness (CIMT) change over 2 years in overweight Latino adolescents and examine its relationship to cardiometabolic risk. STUDY DESIGN: Seventy-two healthy overweight male and female Latino adolescents (mean age, 14.5 ± 1.7 years; mean body mass index, 31.5 ± 6.9 kg/m(2)) were evaluated at baseline and 2 years later for CIMT by high-resolution B-mode ultrasound, the metabolic syndrome and its features, body composition by dual-energy x-ray absorptiometry and magnetic resonance imaging, glucose/insulin measures by fasting blood, and oral and intravenous glucose tolerance tests. RESULTS: Baseline CIMT did not differ from 2-year follow-up; however, 38 participants increased CIMT (0.017 ± 0.003 mm; +2.8%) and 34 decreased or remained the same (-0.019 ± 0.002 mm; -3.1%). ANCOVA analyses showed that participants with CIMT progression had higher baseline low-density lipoprotein (LDL)-cholesterol and total cholesterol (91.3 ± 3.4 and 150.3 ± 3.9 mg/dL) compared with those with CIMT non-progression (78.1 ± 3.6 and 135.6 ± 4.2 mg/dL, P < .05), independent of sex, baseline CIMT, age, and height. In multivariate regression, LDL-cholesterol was the sole predictor of CIMT progression, but the effect was small (odds of CIMT progression increased by 3% for each 1 mg/dL higher baseline LDL-cholesterol; 95% CI, 1.004 to 1.006, P = .03). CONCLUSIONS: These results indicate a high variability in the magnitude of CIMT change in growing overweight Latino youth and support the use of LDL-cholesterol to assess subclinical atherosclerosis risk in this population.

Pubertal changes of insulin sensitivity, acute insulin response, and ß-cell function in overweight Latino youth.

OBJECTIVE: To examine changes in insulin sensitivity (SI), compensatory acute insulin response (AIR), and ß-cell function/disposition index (DI) across puberty in overweight Latino boys and girls. STUDY DESIGN: Latino children (n = 253) were followed annually for up to 5 years. Longitudinal modeling was used to examine changes in SI, AIR, DI, and fasting and 2-hour glucose and insulin across Tanner stage. RESULTS: In boys, SI decreased in early puberty with a recovery by late puberty. The compensatory increase in AIR was appropriate in early maturation, but after Tanner stage 3, AIR declined by more than that predicted from the recovery in SI. For girls, SI decreased in early puberty and across all stages of maturation. In early maturation, there was an appropriate compensatory increase in AIR, but after Tanner stage 3, AIR decreased. Thus, DI deteriorated across puberty in boys and girls. CONCLUSIONS: In overweight Hispanic youth, compensatory changes in insulin secretion fails after Tanner stage 3 in both sexes, indicating ß-cell deterioration during this critical period of development, thus increasing risk for type 2 diabetes.

Persistence of the metabolic syndrome over 3 annual visits in overweight Hispanic children: association with progressive risk for type 2 diabetes.

OBJECTIVE: To examine an association between persistent metabolic syndrome (MetS) and the risk for type 2 diabetes in overweight Hispanic children. STUDY DESIGN: A total of 73 subjects (mean age, 11.0 +/- 1.7 years) from a longitudinal study were classified as Never (negative for MetS at all 3 annual visits), Intermittent (positive for MetS at 1 or 2 visits), or Persistent (positive for MetS at all 3 visits). Measures included dual-energy x-ray absorptiometry, magnetic resonance imaging, the 2-hour oral glucose tolerance test, and the frequently sampled intravenous glucose tolerance test. RESULTS: The Persistent group had a faster rate of fat mass gain than the Never group (20% vs 15% gain of baseline value; P < .05 for time *group interaction [time = visit]). Independent of body composition, the Persistent group increased by 70% in insulin incremental area under the curve, whereas the other groups decreased (P < .05 for time *group interaction). Despite no time *group interactions for insulin sensitivity, acute insulin response, or disposition index, the Persistent group maintained 43% lower insulin sensitivity (P < .01) and by visit 2 had a 25% lower disposition index (P < .05) compared with the Never group. CONCLUSIONS: Patients with persistent MetS had accelerated fat gain, increased insulin response to oral glucose, and decreased sensitivity and beta cell function, indicators of progressively greater risk for type 2 diabetes.