Comparison of β-Cell Function Between Overweight/Obese Adults and Adolescents Across the Spectrum of Glycemia

Abstract

Objective: Type 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in β-cell function along the spectrum of glucose tolerance.

Research design and methods: We evaluated 89 adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and insulin/glucose minimal modeling. Model-derived and direct measures of insulin secretion and insulin sensitivity were compared across glycemic stages and between age-groups at each stage.

Results: In adolescents with dysglycemia, there was marked insulin resistance (insulin sensitivity index: adolescents, median [interquartile range] 1.8 [1.1-2.4] × 10^-4; adults, 5.0 [2.3-9.9]; P = 0.01). The nature of β-cell dysfunction across stages of dysglycemia differed between the groups. We observed higher levels of secretion among adolescents than adults (total insulin secretion: NGT, 143 [103-284] × 10^-9/min adolescent vs. 106 [71-127], P = 0.001); adults showed stepwise impairments in static insulin secretion (NGT, 7.5 [4.0-10.3] × 10^-9/min; dysglycemia, 5.0 [2.3-9.9]; type 2 diabetes, 0.7 [0.1-2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in dynamic secretion (NGT, 1,905 [1,630-3,913] × 10^-9; dysglycemia, 2,703 [1,323-3,637]; type 2 diabetes, 1,189 [269-1,410]; P = 0.001).

Conclusions: Adults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of β-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults.

Figure 1

Comparisons between adults and adolescents in modeled parameters of insulin sensitivity and β-cell function across stages of glycemia. Top left panel: Insulin sensitivity (Si). Top right panel: Φd. Bottom left panel: Φs. Bottom right panel: Φt. DYS, dysglycemia; T2D, type 2 diabetes. Box plot presentation, with the bottom and top of the box presenting the 25th and 75th percentiles, respectively, and the middle line presenting the median. Whiskers present the 5th (bottom) and 95th (top) percentiles; filled circles outside of the whiskers represent individual data points that lie outside this distribution. Four such data points are above the scale for the Φs adolescent DYS group, as is one data point for the Φt adolescent T2D group. *Indicates statistical difference between adult and adolescent groups.

Figure 2

DI curves for normoglycemic adults and adolescents. Insulin sensitivity (Si) is plotted against different measures of insulin secretion: IGI, static insulin response (i.e., Φs), dynamic insulin response (i.e., Φd), and total insulin response (i.e., Φt). The mean DI curves for normoglycemic individuals are plotted; mean DI ± SD for adults and adolescents at each clinical stage are overlaid. Black circles, adult with normoglycemia; black squares, adult with dysglycemia; black triangles, adult with type 2 diabetes; dotted line, adolescent DI; solid line, adult DI; white circles, adolescent with normoglycemia; white squares, adolescent with dysglycemia; white triangles, adolescent with type 2 diabetes.