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|The major metabolic defects present in type 2
diabetes mellitus that lead to glucose elevation are: decreased glucose
transport and utilization at the level of muscle and adipose tissue,
increased glucose production by the liver, and relatively insufficient
insulin secretion by the pancreas. Added to this abnormal flux is any
dietary carbohydrate that is absorbed as glucose or converted to glucose
during the absorptive or postabsorptive process.
Sulfonylureas, the oldest oral agents used to treat type 2 diabetes, stimulate pancreatic insulin secretion. More recently, repaglinide, a meglitinide, has been added to the available agents that stimulate increased pancreatic insulin secretion. Insulin administration, the oldest pharmacologic therapy for diabetes, is also a choice to increase circulating insulin levels in response to failing beta-cell function and increased insulin resistance. Biguanides increase the sensitivity of the liver to circulating insulin, thereby reducing the level of glucose produced by the liver in type 2 diabetes.
Thiazolidinediones, peroxisome proliferator-activated receptors, act at a number of sites to lower blood glucose levels. They also improve insulin sensitivity at the level of the liver, thereby decreasing the excess glucose production by that organ. They are more commonly recognized for their action in increasing peripheral insulin sensitivity in muscle and adipose tissue. By improving this sensitivity, they allow for improvement in the utilization of glucose by the muscle and adipose tissue. It should be noted that biguanides, in high doses, also have some mild effect on increasing peripheral glucose utilization.
Alpha-glucosidase inhibitors decrease the rapid influx of carbohydrate from ingested food and slow the digestion of starches and the absorption of glucose and several other sugars.
Sonnenberg GE, Kotchen TA. Curr Opin Nephrol Hypertens. 1998;7:551-555.