Beta-cell dysfunction and glucose intolerance: Results from the San Antonio metabolism (SAM) study

A. Gastaldelli, E. Ferrannini, Y. Miyazaki, M. Matsuda, R. A. DeFronzo

Research output: Contribution to journalArticlepeer-review

273 Scopus citations


Aims/hypothesis. Both insulin resistance and beta-cell dysfunction play a role in the transition from normal glucose tolerance (NGT) to Type 2 diabetes (T2DM) through impaired glucose tolerance (IGT). The aim of the study was to define the level of glycaemia at which beta-cell dysfunction becomes evident in the context of existing insulin resistance. Methods. Insulin response (OGTT) and insulin sensitivity (euglycaemic insulin clamp) were evaluated in 388 subjects in the San Antonio Metabolism (SAM) study (138 NGT, 49 IGT and 201 T2DM). In all subjects the insulin secretion/insulin resistance index (ΔI/ΔG÷IR) was calculated as the ratio of the increment in plasma insulin to the increment in plasma glucose during the OGTT divided by insulin resistance, as measured during the clamp. Results. In lean NGTs with a 2-h plasma glucose concentration (2-h PG) between 5.6 and 6.6 and between 6.7 and 7.7 mmol/l, there was a progressive decline in ΔI/ΔG÷IR compared with NGTs with a 2-h PG less than 5.6 mmol/l. There was a further decline in ΔI/ΔG÷IR in IGTs with a 2-h PG between 7.8 and 9. 3 and between 9.4 and 11.0 mmol/l, and in Type 2 diabetic patients with a 2-h PG greater than 11.1 mmol/l. Lean and obese subjects showed coincident patterns of relation of 2-h PG to ΔI/ΔG÷IR. Conclusion/interpreation. When the plasma insulin response to oral glucose is related to the glycaemic stimulus and severity of insulin resistance, there is a progressive decline in beta-cell function that begins in "normal" glucose tolerant individuals.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
Issue number1
StatePublished - Jan 2004


  • Beta-cell function
  • Diabetes
  • Glucose tolerance
  • IGT
  • Insulin resistance
  • Insulin secretion
  • NGT
  • OGTT

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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