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

Author:

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

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.

Funder

National Institutes of Health

Publisher

American Diabetes Association

Subject

Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine

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