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

Diabetes Care. 2018 Aug;41(8):1707-1716. doi: 10.2337/dc18-0243. Epub 2018 Jun 25.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / analysis*
  • Blood Glucose / metabolism*
  • C-Peptide / metabolism
  • Child
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Fasting / blood
  • Female
  • Glucose Intolerance / blood
  • Glucose Intolerance / metabolism*
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Insulin Resistance* / physiology
  • Insulin-Secreting Cells / metabolism
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT01779362
  • ClinicalTrials.gov/NCT01779375
  • ClinicalTrials.gov/NCT01763346