Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test

Abstract

Objective: To compare oral glucose tolerance test (OGTT) glucose, C-peptide, and insulin responses and insulin sensitivity in youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes.

Research design and methods: A total of 66 youth (80.3% with IGT) and 355 adults (70.7% with IGT) underwent a 3-h OGTT to assess 1) insulin sensitivity (1/fasting insulin), 2) C-peptide index (CPI) and insulinogenic index (IGI) over the first 30 min, and 3) glucose, C-peptide, and insulin incremental areas above fasting over the 3-h post-ingestion (incremental glucose [G-iAUC], incremental C-peptide [CP-iAUC], and incremental insulin area under the curve [I-iAUC] responses, respectively).

Results: Fasting, 2-h glucose, and G-iAUC were similar in both age-groups, but youth had ∼50% lower 1/fasting insulin (P < 0.001), 75% higher CPI (mean [95% CI] 0.703 [0.226, 2.183] vs. 0.401 [0.136, 1.183] nmol/mmol; P < 0.001), and more than twofold higher IGI (257.3 [54.5, 1,215.8] vs. 114.8 [28.0, 470.8] pmol/mmol; P < 0.001). Two-hour C-peptide and insulin concentrations, CP-iAUC, and I-iAUC were all higher in youth (all P < 0.001). C-peptide and insulin responses remained significantly greater in youth after adjustment for insulin sensitivity. Within each age-group, individuals with type 2 diabetes versus IGT had significantly lower CPI and IGI with no difference in insulin sensitivity.

Conclusions: The balance between insulin sensitivity and β-cell responses differs between youth and adults with IGT or recently diagnosed type 2 diabetes. Despite similar postload glucose levels, youth demonstrate greater C-peptide and insulin responses that exceed what is needed to compensate for their lower insulin sensitivity. Longitudinal studies are required to determine whether this feature contributes to a more rapid decline in β-cell function in youth with dysglycemia.

Trial registration: ClinicalTrials.gov NCT01779362 NCT01779375 NCT01763346.

Figure 1

Plasma glucose, C-peptide, and insulin concentrations during the OGTT in youth and adults (A–C), youth with IGT and diabetes (D–F), and adults with IGT and diabetes (G–I). Youth are shown in red, adults in blue, IGT in green, and diabetes in purple. Data are mean ± SEM. In youth and adults, at all time points following glucose ingestion, glucose concentrations were similar except at 60 min (P = 0.037). C-peptide and insulin were greater in youth at all time points (P ≤ 0.009). In IGT and diabetes, in both youth and adults, the glucose values were greater in diabetes compared with IGT (all P < 0.001). In youth, although the differences were large, they only reached significance at 20 min for C-peptide (P = 0.040) and 10–30 min for insulin (P < 0.05). In adults, both C-peptide and insulin were greater in IGT from 20 to 90 min (P < 0.05).

Figure 2

Relationship of insulin sensitivity (1/FI) with the CPI and IGI from the OGTT in youth and adults (A and B, respectively) and those with IGT and diabetes (C and D, respectively). Youth are shown in red, adults in blue, IGT in green, and diabetes in purple. CPI and IGI are presented on a log scale. The slopes relating early β-cell response measures to insulin sensitivity were all significant (P < 0.001), and the group differences were all significant (youth vs. adults: P < 0.001 for CPI and IGI; IGT vs. diabetes: P < 0.001 for CPI and IGI). The slopes for youth and adults did not differ (P = 0.577 for CPI and P = 0.563 for IGI), whereas in IGT and diabetes, that for CPI did not differ (P = 0.074) but for IGI did (P = 0.007).

Figure 3

Relationship in youth and adults of the OGTT 2-h glucose concentration (A–C) and glucose excursion determined as G-iAUC (D–F) with insulin sensitivity (1/FI; A and D), CPI (B and E), and IGI (C and F), respectively. Youth are shown in red and adults in blue. The slopes relating the 2-h glucose concentration and G-iAUC to insulin sensitivity were not significant in youth or adults (P = 0.373–0.900). For calculation of the slopes relating the 2-h glucose concentration and G-iAUC to CPI and IGI, the β-cell responses were log transformed. Slopes relating the 2-h glucose concentration to CPI and IGI were all significant (P < 0.001 for youth and adults for CPI and adults for IGI; P = 0.003 for youth for IGI), and the group differences were significant (P = 0.004 for CPI and P = 0.034 for IGI). Slopes relating G-iAUC to CPI and IGI were all significant (P < 0.001 for youth and adults for CPI and adults for IGI; P = 0.001 for youth for IGI), and the group differences were significant (P < 0.001 for CPI and P = 0.009 for IGI). For the 2-h glucose, the slopes for youth and adults did not differ (P = 0.476 for 1/FI; P = 0.806 for CPI; and P = 0.852 for IGI). Likewise, for G-iAUC, the slopes for youth and adults did not differ (P = 0.858 for 1/FI; P = 0.665 for CPI; and P = 0.623 for IGI).