Article

Diabetologia

, Volume 47, Issue 1, pp 31-39

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

  • A. GastaldelliAffiliated withMetabolism Unit, C.N.R. Institute of Clinical PhysiologyDiabetes Division, University of Texas Health Science Center
  • , E. FerranniniAffiliated withMetabolism Unit, C.N.R. Institute of Clinical PhysiologyDepartment of Internal Medicine, University of Pisa School of MedicineDiabetes Division, University of Texas Health Science Center
  • , Y. MiyazakiAffiliated withDiabetes Division, University of Texas Health Science Center
  • , M. MatsudaAffiliated withDiabetes Division, University of Texas Health Science Center
  • , R. A. DeFronzoAffiliated withDiabetes Division, University of Texas Health Science Center Email author 

Abstract

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.

Keywords

Diabetes glucose tolerance OGTT insulin resistance insulin secretion beta-cell function IGT NGT