Disturbances in β-Cell Function in Impaired Fasting Glycemia

  1. Timon W. van Haeften1,
  2. Walkyria Pimenta2,
  3. Asimina Mitrakou3,
  4. Mary Korytkowski4,
  5. Trond Jenssen5,
  6. Hannele Yki-Jarvinen6 and
  7. John E. Gerich7
  1. 1Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
  2. 2Department of Internal Medicine, Estadual Paulista University, Botucatu, Brazil
  3. 3Diabetes Center Henry Dunant, Athens, Greece
  4. 4Department of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania
  5. 5Department of Internal Medicine, Oslo University, Oslo, Norway
  6. 6Department of Diabetes, University of Helsinki, Helsinki, Finland
  7. 7Department of Endocrinology, University of Rochester, Rochester, New York

    Abstract

    In a cross-sectional study, we assessed β-cell function and insulin sensitivity index (ISI) with hyperglycemic clamps (10 mmol/l) in 24 subjects with impaired fasting glycemia (IFG, fasting plasma glucose [FPG] between 6.1 and 7.0 mmol/l), 15 type 2 diabetic subjects (FPG >7.0 mmol/l), and 280 subjects with normal fasting glycemia (NFG, FPG <6.1 mmol/l). First-phase insulin release (0–10 min) was lower in IFG (geometric mean 541 pmol/l · 10 min; 95% confidence interval [CI] 416–702 pmol/l · 10 min) and in type 2 diabetes (geometric mean 376 pmol/l · 10 min; 95% CI 247–572 pmol/l · 10 min) than NFG (geometric mean 814 pmol/l · 10 min; 95% CI 759–873 pmol/l · 10 min) (P < 0.001). Second-phase insulin secretion (140–180 min) was also lower in IFG (geometric mean 251 pmol/l; 95% CI 198–318 pmol/l; P = 0.026) and type 2 diabetes (geometric mean 157 pmol/l; 95% CI 105–235 pmol/l; P < 0.001) than NFG (geometric mean 295 pmol/l; 95% CI 276–315 pmol/l). IFG and type 2 diabetic subjects had a lower ISI (0.15 ± 0.02 and 0.16 ± 0.02 μmol/kg fat-free mass [FFM]/min/pmol/l, respectively) than NFG (0.24 ± 0.01 μmol/kg FFM/min/pmol/l, P < 0.05). We found a stepwise decline in first-phase (and second-phase) secretion in NFG subjects with progressive decline in oral glucose tolerance (P < 0.05). IFG subjects with impaired glucose tolerance (IGT) had lower first-phase secretion than NFG subjects with IGT (P < 0.02), with comparable second-phase secretion and ISI. NFG and IFG subjects with a diabetic glucose tolerance (2-h glucose >11.1 mmol/l) had a lower ISI than their respective IGT counterparts (P < 0.05). We conclude that the early stages of glucose intolerance are associated with disturbances in β-cell function, while insulin resistance is seen more markedly in later stages.

    Footnotes

    • Address correspondence and reprint requests to t.w.vanhaeften{at}azu.nl.

      Accepted for publication 25 June 2001.

      DGT, diabetic glucose tolerance;FFM, fat-free mass;FPG, fasting plasma glucose;GIR, glucose infusion rate;IFG, impaired fasting glycemia;IGT, impaired glucose tolerance; NFG, normal fasting glycemia; ISI, insulin sensitivity index; LBM, lean body mass; OGTT, oral glucose tolerance test;WHR, waist-to-hip ratio.

      The symposium and the publication of this article have been made possible by an unrestricted educational grant from Servier, Paris.

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