Type 2 Diabetes Mellitus

Hyperglycemia is due to a variable combination of overproduction of glucose by the liver and impaired insulin-stimulated tissue glucose uptake. Hyperglycemia, through a mass action effect, results in enhanced non-insulin-mediated glucose uptake by tissues other than brain (including insulin target tissues), thereby compensating to a variable extent for impaired insulin-mediated glucose uptake. The contributions of

The “glucotoxicity” theory holds that some of the β-cell defects are secondary to chronic hyperglycemia. Support for the theory comes from (1) studies showing that prolonged exposure of rat or human islets to high glucose levels can induce a number of defects, and (2) the observation that the absent first-phase insulin response and defective glucose

In IGT insulin secretion may be normal, increased, or decreased. This variability is partly due to the heterogeneity of this category and partly due to confounding effects of obesity and insulin resistance, which are associated with enhanced insulin secretion in normoglycemic subject. However, compared to normoglycemic subjects matched for degree of insulin resistance and obesity,

Insulin resistance may be defined as a subnormal biologic response to a given concentration of insulin. The most widely used methods of estimating insulin sensitivity with respect to glucose metabolism are the glucose clamp and the minimal model. With both methods, type 2 diabetic patients and obese non diabetic subjects are characteristically less insulin sensitive

Hyperglycemia is often accompanied by increased levels of the gluconeogenic precursors, lactate, alanine, pyruvate, and glycerol. Lipolysis is often increased, particularly in obese patients and those with poor insulin secretion resulting in elevated fasting and postprandial plasma free fatty acid (FFA) levels and increased hepatic VLDL production. Under normal circumstances enough insulin is present to