Hemoglobin A1c above Threshold Level is Associated with Decreased β-Cell Function in Overweight Latino Youth

ObjectiveTo examine whether a hemoglobin A1c (HbA1c)-identified prediabetic state (HbA1c ≥6.0%-6.4%) is associated with decreased insulin sensitivity (SI) and β-cell dysfunction, known factors in the pathogenesis of type 2 diabetes, in an overweight pediatric population.Study designA 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 β-cell function) by the frequently sampled intravenous glucose tolerance test with minimal modeling. Body fat was determined by dual-energy X-ray absorptiometry.ResultsCompared 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.ConclusionThese data provide clear evidence of greater impairment of β-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.