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

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. A total of 66 youth (80.3% with IGT) and 355 adults (70.7% with IGT) underwent a 3-h OGTT to assess <i>1</i>) insulin sensitivity (1/fasting insulin), <i>2</i>) C-peptide index (CPI) and insulinogenic index (IGI) over the first 30 min, and <i>3</i>) 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). Fasting, 2-h glucose, and G-iAUC were similar in both age-groups, but youth had ∼50% lower 1/fasting insulin (<i>P</i> < 0.001), 75% higher CPI (mean [95% CI] 0.703 [0.226, 2.183] vs. 0.401 [0.136, 1.183] nmol/mmol; <i>P</i> < 0.001), and more than twofold higher IGI (257.3 [54.5, 1,215.8] vs. 114.8 [28.0, 470.8] pmol/mmol; <i>P</i> < 0.001). Two-hour C-peptide and insulin concentrations, CP-iAUC, and I-iAUC were all higher in youth (all <i>P</i> < 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. 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.