Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp
Author:
, Ehrmann David A.1, Temple Karla A.1, Rue Abby1, Barengolts Elena1, Mokhlesi Babak1, Van Cauter Eve1, Sam Susan1, Miller M. Annette1, Kahn Steven E.1, Atkinson Karen M.1, Palmer Jerry P.1, Utzschneider Kristina M.1, Gebremedhin Tsige1, Kernan-Schloss Abigail1, Kozedub Alexandra1, Montgomery Brenda K.1, Morse Emily J.1, Mather Kieren J.1, Garrett Tammy1, Hannon Tamara S.1, Lteif Amale1, Patel Aniket1, Chisholm Robin1, Moore Karen1, Pirics Vivian1, Pratt Linda1, Nadeau Kristen J.1, Gross Susan1, Zeitler Philip S.1, Williams Jayne1, Cree-Green Melanie1, Garcia Reyes Yesenia1, Vissat Krista1, Arslanian Silva A.1, Brown Kathleen1, Guerra Nancy1, Porter Kristin1, Caprio Sonia1, Savoye Mary1, Pierpont Bridget1, Buchanan Thomas A.1, Xiang Anny H.1, Trigo Enrique1, Beale Elizabeth1, Hendee Fadi N.1, Katkhouda Namir1, Nayak Krishan1, Martinez Mayra1, Montgomery Cortney1, Wang Xinhui1, Edelstein Sharon L.1, Lachin John M.1, Hogan Ashley N.1, Marcovina Santica1, Harting Jessica1, Albers John1, Hill Dave1, Savage Peter J.1, Leschek Ellen W.1
Affiliation:
1. RISE Coordinating Center, Rockville, MD
Abstract
OBJECTIVE
To compare insulin sensitivity (M/I) and β-cell responses in youth versus adults with impaired glucose tolerance (IGT) or drug-naïve, recently diagnosed type 2 diabetes.
RESEARCH DESIGN AND METHODS
In 66 youth (80.3% with IGT) and 355 adults (70.7% IGT), hyperglycemic clamps were used to measure 1) M/I, 2) acute (0–10 min [first phase]) C-peptide (ACPRg) and insulin (AIRg) responses to glucose, 3) steady-state C-peptide and insulin concentrations at plasma glucose of 11.1 mmol/L, and 4) arginine-stimulated maximum C-peptide (ACPRmax) and insulin (AIRmax) responses at plasma glucose >25 mmol/L. The fasting C-peptide–to–insulin ratio was used as an estimate of insulin clearance.
RESULTS
Insulin sensitivity was 46% lower in youth compared with adults (P < 0.001), and youth had greater acute and steady-state C-peptide (2.3- and 1.3-fold, respectively; each P < 0.001) and insulin responses to glucose (AIRg 3.0-fold and steady state 2.2-fold; each P < 0.001). Arginine-stimulated C-peptide and insulin responses were also greater in youth (1.6- and 1.7-fold, respectively; each P < 0.001). After adjustment for insulin sensitivity, all β-cell responses remained significantly greater in youth. Insulin clearance was reduced in youth (P < 0.001). Participants with diabetes had greater insulin sensitivity (P = 0.026), with lesser C-peptide and insulin responses than those with IGT (all P < 0.001) but similar insulin clearance (P = 0.109).
CONCLUSIONS
In people with IGT or recently diagnosed diabetes, youth have lower insulin sensitivity, hyperresponsive β-cells, and reduced insulin clearance compared with adults. Whether these age-related differences contribute to declining β-cell function and/or impact responses to glucose-lowering interventions remains to be determined.
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
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