From STOP the Rollerocaster
Copyright © 1996 by Diabetes Services, Inc.
Cell health depends on a steady supply of fuel from glucose and free fatty acids. These two major fuels are both regulated by insulin released directly into the blood from beta cells in the pancreas. From the blood, an insulin molecule crosses the blood vessel wall and attaches to an insulin receptor on the outer wall of a muscle, liver or fat cell. This attachment triggers the movement of glucose into the interior of the cell, where it can be converted into energy for metabolism, repair and defense.
In contrast to the complicated transport system for glucose, and to the chagrin of many, fat moves easily across cell membranes. If insulin levels are too low, less glucose enters cells, but more glucose is released by the liver and more fat is released from fat cells. So a low insulin level causes not only a high blood sugar but it also causes more fat to enter the blood.
Cells in the muscle, liver, and fat need insulin to receive glucose. The first group of cells that need insulin, those in muscle, liver, and fat, do not become exposed to high internal glucose levels when the blood sugars are high and insulin levels are low. The lack of insulin slows the movement of glucose into these cells, and probably spares them from damage when blood sugars are high.
However, other cells such as those in the brain, nervous system, heart, blood vessels and kidneys pick up glucose directly from the blood without using insulin. These cells, except the brain, are more prone to damage from high blood sugars because they become exposed to high internal levels of glucose.
This is one reason why damage tends to occur in these areas of the body, such as in nerve and kidney cells, and in small blood vessels like those in the eyes. They always have their "doors open" to glucose. When blood sugars are high, these cells have high interior glucose levels. The excess glucose makes it impossible for cells or organs to function as they are meant to. They fail to produce key enzymes, fail to repair themselves and fail to transport nutrients needed in the cells.
Nerve cells, are vulnerable also because of their shape. Many nerve cells are extremely long compared to their width. Each nerve depends on thousands of tiny blood vessels along its path to receive oxygen, fuel, and other nutrients. If one or more of these supporting microvessels become damaged, that part of the nerve is also damaged. Electrical signals in these damaged nerves can then no longer pass, or they pass at a slower speed. This dependence on numerous small blood vessels is why the longest nerves going to the feet are the first to be damaged in neuropathy. Good messaging in nerves also depends on an outer protective coating called myelin. This electrical insulator is also vulnerable to damage from high blood sugars.
Eyes are vulnerable because blood flow to the retina is driven by the need for oxygen. The small blood vessels in the retina (on the back wall of the eye where nerves receive incoming light) have no muscles to limit blood flow. When oxygen is less available (which is worsened by smoking and inactivity) the normal controls on excessive blood flow break down. Blood then engorges the small vessels in the retina where oxygen is low. For instance, when the blood sugar climbs from 100 mg/dl (5.6 mmol) to 400 mg/dl (22 mmol), blood flow to the retina rises to five times its normal levels in a short period of time. This excessive blood flow and blood pressure to the small blood vessels in the retina creates an environment highly likely to cause damage. This is especially true when a balancing pressure in the vitreous, the clear gel in the middle of the eye, is low.71
Heart damage is caused by the same risk factors found in the general population. But these risks become magnified by high blood sugars. High blood sugars create harmful changes in LDL, HDL, and triglyceride levels, increased clotting, higher blood pressure, and altered blood flow. People with diabetes have other, as yet unexplained, risks. The standard heart risks magnified by high blood sugars do not explain all of the excess heart damage seen in diabetes. Some possible explanations are discussed in the next chapter.
Brain cells, in contrast to nerve cells, appear to be relatively protected even though glucose is their only source of energy and their "doors" are always open. The brain may derive this protection from the blood-brain barrier and from having different glucose transporters than those found in other organs. Glucose levels in brain cells are normally only one third the levels found in the blood! 72 These factors provide a relative degree of protection to the brain.
However, IQ levels were found to drop temporarily in Australian children as their blood sugars rose. When the children's blood sugar climbed to 400 mg/dl (22 mmol), their IQ dropped by 10 percent.73 Fortunately, this loss of intelligence was corrected when blood sugars were brought back down.
But research in Kansas found that a permanent loss of IQ seems to occur following ketoacidosis that requires hospitalization. Each ketoacidosis episode, with its high blood sugars, in the children studied appeared to cause a loss of just over one point in the IQ. (Although low blood sugars can certainly cause a temporary impairment of consciousness and reasoning, these researchers found no permanent effect on the IQ from severe hypoglycemia in these children.74 Very severe and prolonged hypoglycemia can cause this type of loss, however.)