What Happens on the Cellular Level to Cause Type 2 Diabetes?

The key difference between type 1 and type 2 diabetes is that while people with type 1 diabetes do not produce enough insulin, people with type 2 diabetes can have normal or even high levels of insulin.

Insulin resistance usually precedes the onset of type 2 diabetes. A person can become insulin deficient because of a genetic predisposition, or because of obesity and a sedentary lifestyle. Insulin resistance interferes with insulin's ability to perform its many important functions.

When the level of glucose in the blood is high, beta cells within the pancreas release insulin into the bloodstream. The insulin helps to move glucose into cells in the body's tissues, such as muscles. Insulin also speeds up the conversion of glucose into glycogen, which cells store and use for energy; increases the uptake of amino acids (the building blocks of proteins) and the synthesis of protein in cells; speeds fatty acid synthesis, slows the breakdown of glycogen, and slows the production of more glucose by the liver. This process prevents blood glucose levels from getting too high, and supplies cells with the energy and protein they need to function properly.

When a person has a genetic condition that causes her to have abnormal beta cells in her pancreas, she can develop type 2 diabetes even if she is otherwise healthy. However, most cases of type 2 diabetes occur in obese people over the age of 35. A person who is obese, especially around the waist, and who gets very little physical exercise, can get into a cycle of insulin and blood glucose imbalance that can lead to type 2 diabetes.

When blood glucose is often high, as in a person with a poor diet and inadequate exercise, the receptors in cells that detect and react to the insulin can become less sensitive. This process may be similar to how a person who walks into a house where bread is baking smells the bread immediately, but no longer notices the smell after spending a few minutes in the house because the scent receptors in his nose are no longer reacting to the smell of the bread.

When cells in body tissues do not react properly to the insulin that the pancreas has released, the glucose level in the blood stays higher than it should be. The pancreas detects that blood glucose is too high, and releases more insulin. This will be adequate at first, but the receptors in the cells can adapt to the new level of insulin and become less sensitive to it. Then the pancreas must release even more insulin, which makes the cells less sensitive to insulin, and so on. Eventually, the beta cells can no longer keep up with the increased demand for insulin, and the blood glucose stays high---this is type 2 diabetes. High blood glucose causes excessive thirst, and lack of glucose and glycogen within the cells causes fatigue---these are two classic symptoms of diabetes.

While type 2 diabetes used to be called "adult onset" diabetes because it is usually seen in people over 35, the increase in childhood obesity has led to many more cases of type 2 diabetes in teenagers and even children. Because diabetes is associated with blindness, limb amputation, kidney failure, heart attack and stroke, this is a major public health concern. The American Heart Association and the National Heart, Lung and Blood Institute include abdominal obesity, insulin resistance and glucose intolerance as three out of six components of metabolic syndrome, which is a major risk factor for heart disease and stroke, and the risk rises sharply when diabetes becomes clinically apparent. Because more than 90% of all cases of diabetes are type 2, reducing the incidence of type 2 diabetes could greatly reduce the incidence of heart disease and stroke.

References

• The Pathophysiology of Type 2 Diabetes: New Perspectives and Their Clinical Impact; Paul S. Jellinger, MD, MACE
• Definition of Metabolic Syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition: Scott M. Grundy, MD, PhD; H. Bryan Brewer, Jr, MD; James I. Cleeman, MD; Sidney C. Smith, Jr, MD; Claude Lenfant, MD, for the Conference Participants*
• Principles of Anatomy and Physiology; Gerard Tortora and Bryan Derrickson; 2006

Resources

• CDC---exercise recommendations
• Mayo Clinic---metabolic syndrome
• American Diabetes Association---diabetes symptoms