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Homeostasis

Author(s): Wade Haaland

Type 2 Diabetes Mellitus

Type 2 diabetes is most common in older individuals, because it takes time for this disease to develop (for this reason, we say it has an insidious onset). The classic model of Type 2 diabetes shows us that over time, the peripheral tissues become insulin resistant. In other words, the body is no longer responding to the insulin signal. Therefore, after glucose ingestion, even in the presence of insulin, the blood glucose concentration remains too high. Furthermore, because the liver is also resistant to insulin, glycogenolysis and gluconeogenesis are not terminated. Thus, the body has a high blood glucose concentration due to the inability of the peripheral tissues to take in glucose AND because the liver is synthesizing glucose. 

As seen in the simplified second graph, β-cell Insulin Production v. Time, we see that the β-cell compensates for resistance by increasing the production of insulin. The β-cell is able to produce enough insulin to overcome the resistance and maintain normal blood glucose levels. However, eventually, the β-cell becomes exhausted from this work over-load. At that point, the peripheral tissues are resistant to insulin and the body is not producing enough insulin for a normal individual.

This process does not happen overnight. As the graph illustrates, an individual may have normal glucose homeostasis for the majority of his/her life. However, as insulin resistance progresses and β-cell function is diminished, a person will become "pre-diabetic." At this stage of the disease, a person may not know that he/she is affected. Nonetheless, his or her body is gradually losing its ability to control blood glucose levels. As the disease progresses, full-blown diabetes ensues and treatment options become more and more limited.

Although insulin resistance usually develops over years, there is an alarming increase in the incidence of Type 2 diabetes among children. Many believe this trend is a result of less active children who may not be exercising sufficiently or eating healthy foods.

Diabetes is a complex disease, and as you have learned from the previous slides, there is more than one way to become diabetic. The end result is the same for both Type 1 and Type 2 diabetes, if left untreated: loss of glucose homeostasis, which can be fatal.