The Glucose Tolerance Test as a Laboratory Tool with Clinical Implications

Metabolic syndrome is a cluster of abnormalities that are often associated with prediabetes, a condition present prior to the onset of diabetes (1). The hallmark of both metabolic syndrome and prediabetes is insulin resistance, an impairment of insulin action within tissues at the level of the insulin receptor and subsequent cellular events. Insulin resistance resides mainly within muscle, liver and adipose tissues (2). Type 2 diabetes arises from a combination of insulin resistance and a relative impairment of insulin secretion in response to meal ingestion. Type 2 diabetics differ in the relative contributions of insulin resistance and impaired insulin secretion to the development of hyperglycemia (3). Some diabetic patients predominantly have a secretory defect, while others may have normal or even excessive insulin secretion. The latter subgroup of diabetics has insulin resistance as the primary defect in their glucose homeostasis. Hyperglycemia by itself does not indicate whether there is an insufficiency of insulin secretion or a deficit in insulin action. Type 2 diabetics lie along a continuum between these two extremes, with a variable mix of secretory and cell signaling deficits. During the progression from normal glucose tolerance to impaired glucose tolerance to prediabetes to diabetes to severe diabetes over a number of years, individuals show a progressive decline in pancreatic insulin secretion in response to a glucose load(3). Insulin resistance may show progressive deterioration, but generally insulin resistance is the major defect early in the development of diabetes whereas late in the course of the disease pancreatic islet cell failure is more notable.