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

Abstract

Objective: To 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 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 β-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 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.

Figure 1

A) Insulin sensitivity, B) Acute Insulin Response, C) Disposition Index. ANCOVAs were performed on log-transformed data and results were then back-transformed for figure presentation. SI and DI estimated marginal means (EMM) are shown ± SE and are adjusted for age and total percent body fat. AIR EMM was also adjusted for SI. *p<0.05, **p<0.01, ***p<0.001

Figure 2

A) Insulin sensitivity, B) Acute Insulin Response, C) Disposition Index. ANCOVAs were performed on log-transformed data and results were then back-transformed for figure presentation. SI and DI estimated marginal means (EMM) are shown ± SE and are adjusted for age and total percent body fat. AIR EMM was also adjusted for SI. *p<0.05, **p<0.01, ***p<0.001