The relationship between fasting hyperglycemia and insulin secretion in subjects with normal or impaired glucose tolerance

Muhammad A. Abdul-Ghani, Masafumi Matsuda, Rucha Jani, Christopher P. Jenkinson, Dawn K. Coletta, Kohei Kaku, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT (n = 293) and IGT (n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as ΔISR/ΔG ÷ IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(-0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0-30 min) was correlated with the increase in FPG in both NGT and IGT (r = -0.43, P < 0.0001 and r = -0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60-120 min) and FPG was not significant. In conclusion, small increments in FPG, within the "normal" range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.

Original languageEnglish (US)
Pages (from-to)E401-E406
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2
StatePublished - Aug 2008
Externally publishedYes


  • Fasting plasma glucose
  • β-cell function

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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