Hemoglobin A1c above Threshold Level is Associated with Decreased b-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 b-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 AE 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 b-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 AE 0.06 vs 1.54 AE 0.13; P < .05), 30% lower acute insulin response (928 AE 102 vs 1342 AE 56; P < .01), and a 31% lower disposition index (1390 AE 146 vs 2023 AE 83; P = .001) after adjusting for age and total percent body fat. Conclusion These data provide clear evidence of greater impairment of b-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. (J Pediatr 2012;160:751-6). M ore than 40% of the US population suffers from diabetes or prediabetes