Comparison of β-Cell Function Between Adults and Adolescents with Dysglycemia

Presentation Number: SUN 592
Date of Presentation: April 2nd, 2017

Melinda Chen*1, Aaditya Chandramouli2, Tamara S Hannon1 and Kieren J. Mather1
1Indiana University School of Medicine, Indianapolis, IN, 2Indiana University School of Medicine

Abstract

Progressive impairment in β-cell function from normoglycemia through dysglycemia to type 2 diabetes has been described using direct measurements and model-based approaches. It is unknown whether the pattern of decline in β-cell function across this progression fundamentally differs between adults and adolescents.

Insulin and c-peptide responses to standard 75g oral glucose tolerance tests were evaluated as traditional incremental responses, and fitted to minimal models using SAAM II modeling software to derive total, static and dynamic components of β-cell function and their respective disposition indices.

Results from 50 adolescents (BMI 39.0 ±8.2 kg/m2, 12-18 y) and 71 adults (BMI 30.0 ±6.9 kg/m2, 22-66 y) were analyzed, with results from 39 adolescents and 62 adults available for concurrent analysis of c-peptide and insulin sensitivity modeling. Adolescents and adults both showed progressive worsening of β-cell function by direct measurements (e.g. normal vs type 2 diabetes insulinogenic index (IGI) 3.57 ± 1.96 vs 0.91 ± 0.63, p<0.001 in adolescents, 2.77 ± 3.08 vs 0.76 ± 0.76, p=0.065 in adults) across the clinical stages of dysglycemia. Differences in modeled components of β-cell secretion across clinical stages were most apparent in the dynamic component (phi D) of insulin secretion, with significantly lower disposition indices based on phi-D (DI-phi D) in dysglycemic and type 2 subjects compared to normoglycemic counterparts in both adolescents (normal DI-phi D 1.19 ± 0.79; vs. dysglycemic 0.43 ± 0.38, p=0.02; vs. type 2 diabetes 0.20 ± 0.41, p=0.011) and adults (normal DI-phi D 1.71 ± 1.62; vs. dysglycemic 0.64 ± 0.65, p=0.012; vs. type 2 diabetes 3.02x10-2 ± 3.60x10-2, p<0.001).

Dysglycemic adolescents showed higher insulin production than dysglycemic adults (IGI 5.80 ± 3.76 vs. 1.75 ± 1.34, p=0.005; c-peptide index 0.19 ± 0.11 vs 0.12 ± 0.08, p=0.039), though overall insulin sensitivity was lower in normal and dysglycemic adolescents (normoglycemic insulin sensitivity index (Si) 6.84x10-4 ± 5.70x10-4 adolescents vs 1.39x10-3 ± 1.19x10-3 adults, p=0.021; dysglycemic Si 1.80x10-4 ± 7.11x10-5 vs. 7.52x10-4 ± 5.88x10-4, p<0.001). There were no significant differences in any measures of β-cell function between adolescents and adults with type 2 diabetes.

Adolescents and adults demonstrated differences in the patterns of decline of β-cell function across the progression to type 2 diabetes. In both age groups, β-cell dysfunction was most apparent within the dynamic component of insulin secretion, indicating greater impairment to insulin responsiveness to acute glucose fluctuations. Adolescents developed dysglycemia with higher levels of insulin production coupled with higher insulin resistance, differences which were no longer apparent after development of type 2 diabetes.

 

Nothing to Disclose: MC, AC, TSH, KJM