Insulin Resistance (IR) in Impaired Glucose Tolerance (IGT)

Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes mellitus was described as an early pathogenetic phenomenon[1]. Moreover, impaired action of insulin (insulin resistance) has been associated with pre-diabetic state, impaired glucose tolerance and diabetes mellitus[2]. It is postulated that IR then leads to insulin deficiency. Thus, glucose intolerance develops either as a result of secondary beta-cell failure in a backdrop of insulin resistance (often designated as "beta-cell exhaustion") or as a result of primary beta cell defect. Whether primary or secondary, poorly functioning beta-cells cannot be relied upon to provide insulin while estimating insulin resistance. However, basal or poststimulation insulin levels tend to rise with rising insulin resistance(to maintain euglycaemia), the level will not be reflective of IR in presence of beta-cell deficiency. This occurs in the presence of glucose intolerance. Moreover, by definition of glucose intolerance, the glucose levels achieved on (only) glucose infusion/ingestion would be higher in these conditions. Since hyperglycaemia itself has been implicated in the development of IR, an estimate of IR at different ambient glucose levels cannot be strictly compared. On the issue of methodology of IR, there have been two elegant reviews published recently[3,4].