Taking A Closer Look At Insulin Resistance Syndrome
- Volume 15 - Issue 4 - April 2002
- 6593 reads
- 0 comments
Over 16 million people in the United States have diabetes and this number is growing by the hour. Diabetes is now the fifth leading cause of death in this country.1 By understanding the pathophysiology of diabetes and the environmental factors which contribute to this disease, we can have a better focus on the scope and nature of the threat to our patient population with diabetes.
With this in mind, it’s important to have a thorough knowledge of the potential impact of insulin resistance syndrome, a condition in which the tissues of the body become desensitized to insulin. It is a chronic state that will result in hyperglycemia and its associated complications.
The metabolic manifestation of insulin resistance syndrome include reduced amount of insulin-stimulated glucose uptake; reduced insulin suppression of endogenous glucose production; and reduced antilipolysis.2 With type 2 diabetic patients, there is a loss of early phase insulin secretion, which is also known as beta cell dysfunction.3 The relationship of early insulin secretion to insulin sensitivity in normal individuals is represented by a hyperbolic curve in keeping with the existence of a feedback loop. Deviation from the standard curve demonstrates defects in both insulin secretion and sensitivity in people who are at risk of developing diabetes.4
The reduction of early phase insulin response results in impaired suppression of hepatic glucose production. Therefore, the amount of glucose produced by the liver is not inversely proportional to the amount of glucose influx, and this results in postprandial hyperglycemia.
The target tissues which respond to insulin are chiefly the liver, adipose and indirectly skeletal muscle. Insulin resistance syndrome in the hepatic tissues results in fasting hyperglycemia from the rapid release of glucose from its store of glycogen (glycogenolysis).
In addition, gluconeogenesis converts amino acids, lactate and glycerol released from other tissues into glucose. In the face of insulin resistance, there is no regulation of hepatic glucose uptake and the body is producing glucose to feed the hunger state. Adipose tissue is the most sensitive tissue in the body to insulin. Insulin resistance syndrome results in the accumulation of free fatty acids, promotes lipogenesis and inhibits lipolysis.
In their study, Basu et. al., attempted to determine whether type 2 diabetes mellitus alters systemic and regional free fatty acid metabolism.4 They concluded that type 2 diabetes is associated with a generalized impairment in insulin suppression of lipolysis compared with equally obese non-diabetic individuals. An additional concern is that these circulating free fatty acids can also undergo biosynthesis into cholesterol and phospholipids.4
Skeletal muscle is the other major organ responsible for glucose uptake under the direction of insulin. Ryder et. al., focused their research on the molecular mechanism regulating insulin action and the factors contributing to insulin resistance in skeletal muscle.5 The concluded that type 2 diabetic patients have a defect in insulin signal transduction through the insulin receptor substrate. Secondary to the lack of insulin stimulation, there is decreased uptake of glucose transport. This is a key rate-limiting step in glucose metabolism.5