[Early stages of beta-cell deficiency: the anticipated chronicle to type 2 diabetes]

Type 2 diabetes combines two mechanisms, peripheral insulin resistance and beta-cell defect. In this disease, insulin secretion is rather difficult to evaluate because: 1) the multiplicity of tests exploring different aspects of insulin secretion, 2) the complex relationships between beta-cell function and either insulin resistance or plasma glucose level. In glucose tolerant populations at risk of diabetes, insulin secretion has been found heterogeneous with large inter individual variations. However, insulin secretion is decreased in almost 50% of the studies. In glucose intolerant subjects, insulin secretion is more consistently altered, specially acute insulin response to glucose. More subtle abnormalities, as decrease of proinsulin cleavage or pulsatility, are rare at this stage. When diabetes is diagnosed, beta-cell defect is obvious whatever the test used, and progress with time. The markers of the transition to glucose intolerance are both insulin resistance and acute insulin response. The transition to diabetes is associated with the same factors plus the dysregulation of hepatic glucose production. Hyperinsulinism and high proinsulin/insulin ratio are good predictors of diabetes in at risk populations. Loss of beta-cell function is a major factor in the progressive worsening of the disease, specially in glucose intolerant subjects.