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Original Research
Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp
The RISE Consortium
Diabetes Care 2018 Jun; dc180244. https://doi.org/10.2337/dc18-0244
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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.

Footnotes

  • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0244/-/DC1.

  • ↵* A complete list of the RISE Consortium Investigators can be found in the Supplementary Data online.

  • Received January 31, 2018.
  • Accepted April 28, 2018.
  • © 2018 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp
The RISE Consortium
Diabetes Care Jun 2018, dc180244; DOI: 10.2337/dc18-0244

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Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp
The RISE Consortium
Diabetes Care Jun 2018, dc180244; DOI: 10.2337/dc18-0244
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© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.