Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test
RISE Consortium, David A Ehrmann, Karla A Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M Annette Miller, Steven E Kahn, Karen M Atkinson, Jerry P Palmer, Kristina M Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K Montgomery, Emily J Morse, Kieren J Mather, Tammy Garrett, Tamara S Hannon, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Kristen J Nadeau, Susan Gross, Philip S Zeitler, Jayne Williams, Melanie-Cree Green, Yesenia Garcia Reyes, Krista Vissat, Silva A Arslanian, Kathleen Brown, Nancy Guerra, Kristin Porter, Sonia Caprio, Mary Savoye, Bridget Pierpont, Thomas A Buchanan, Anny H Xiang, Enrique Trigo, Elizabeth Beale, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Sharon L Edelstein, John M Lachin, Ashley N Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage, Ellen W Leschek, RISE Consortium, David A Ehrmann, Karla A Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M Annette Miller, Steven E Kahn, Karen M Atkinson, Jerry P Palmer, Kristina M Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K Montgomery, Emily J Morse, Kieren J Mather, Tammy Garrett, Tamara S Hannon, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Kristen J Nadeau, Susan Gross, Philip S Zeitler, Jayne Williams, Melanie-Cree Green, Yesenia Garcia Reyes, Krista Vissat, Silva A Arslanian, Kathleen Brown, Nancy Guerra, Kristin Porter, Sonia Caprio, Mary Savoye, Bridget Pierpont, Thomas A Buchanan, Anny H Xiang, Enrique Trigo, Elizabeth Beale, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Sharon L Edelstein, John M Lachin, Ashley N Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage, Ellen W Leschek
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.
© 2018 by the American Diabetes Association.
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Source: PubMed