Causes

Causes

Type 2 diabetes is caused by a complicated interplay of genes, environment, insulin abnormalities, increased glucose production in the liver, increased fat breakdown, and possibly defective hormonal secretions in the intestine. The recent dramatic increase indicates that lifestyle factors (obesity and sedentary lifestyle) may be particularly important in triggering the genetic elements that cause this type of diabetes.

Insulin Abnormalities

The characteristic features of most patients with type 2 diabetes are:

• Insulin resistance in muscle cells
• Normal or even excessive levels of insulin (to compensate for this resistance), eventually followed by a drop in insulin production

In addition, researchers are trying to determine the factors that might promote insulin resistance:

• Both obesity and insulin resistance at different phases are marked by elevated levels of free fatty acids and the hormones resistin and leptin. It is not known yet if elevated levels are simply a product of obesity or play some causal role in diabetes.
• Insulin resistance is associated with a chronic low inflammatory response, which involves a number of immune factors, such as TGH-beta 1 and C-reactive protein. Such factors can cause damage over time and may be responsible for the association between insulin resistance and heart disease.

Genetic Factors

Genetic factors play an important role in type 2 diabetes, but the pattern is complicated, since both impairment of beta cell function and an abnormal response to insulin are involved. Researchers have identified a number of genetic factors that may be responsible for selected or more general cases of diabetes:

• Genes responsible for maturity-onset diabetes in youth (MODY), a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. (This is not the diabetes associated with obesity that is now being seen increasingly in young people.)
• A defective fatty-acid binding protein 2 (FABP2) gene, which may result in higher levels of unhealthy fat molecules (particularly triglycerides) that may be critical in the link between obesity and insulin resistance in some people with type 2 diabetes.
• Alterations in five genes that regulate beta cell and pancreas function may play an important role in inherited cases of type 2 diabetes.
• Variations in a gene that regulates a protein called calpain-10 affects insulin secretion and action and may play a role in type 2 diabetes in certain populations. There is some disagreement, however, about its significance. Calpains are enzymes that play a wide role in many essential cellular functions. Evidence suggests that genetic activation of these enzymes may be important in many aging-related diseases.
• Defective genes that regulate a molecule called peroxisome proliferator-activated receptor (PPAR) gamma may contribute to both type 2 diabetes and high blood pressure in some patients.
• A defective gene that reduces activity of a protective substance called beta3-adrenergic receptor, which is found in visceral fat cells (those occurring around the abdominal region), may be responsible for a slow-down in metabolism and an increase in obesity.