Is nagging effective against diabetes juvenile onset diabetes

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Type II diabetes, a metabolic disorder suffered by as many as 15 million Americans, is closely associated with obesity. (1) This connection has led to a common perception that obesity is the cause of diabetes – and sometimes a tendency to blame the victims of this potentially life-threatening disease for their own condition. But the relationship between obesity and diabetes is complex. The report of the American Diabetes Association’s Consensus Development Conference on Insulin Resistance in 1997 found that the mechanism responsible for Type II diabetes has both a primary genetic component and a secondary environmental component. (2) And a recent study indicates that the same genetic agent may contribute to both diabetes and obesity. (3)


Diabetes results from the body’s failure to maintain a stable level of glucose in the blood because of the scarcity or ineffectiveness of a hormone called insulin. Glucose, the six-carbon sugar that is essential to the metabolic processes of all eukaryotic life, (4) is water-soluble, but too large to pass unaided through the phospholipid membranes of animal cells. Its transportation across cell membranes is dependent on insulin, a protein that is secreted by beta cells of the pancreas. The trigger for the production of insulin by the beta cells is glucose, which is absorbed into the bloodstream through the small intestines after eating. (5)

Insulin effects glucose transport by binding to receptors that fit its three-dimensional shape and penetrate the cell membrane. These receptors are most plentiful in muscle cells. When the insulin attaches to the part of the receptor that is outside the cell, it changes the shape of the receptor inside the cell, sending a signal to other molecules inside. These signals initiate a chain of reactions that ultimately bring to the surface of the cell a glucose-transporter protein that brings glucose molecules into the cell through facilitated diffusion. (6) This process includes several intermediate steps involving the transfer of phosphate groups among proteins within the cell; several of these proteins have been identified and studied. (7)

In the liver, insulin stimulates the cells to transform glucose into glycogen, the form in which it is stored. But after the liver has stored about five percent of its weight in glycogen, is stops making glycogen and instead uses the glucose to synthesize fatty acids. These fatty acids eventually find their way to fat cells, which use them to synthesize triglycerides. Insulin also has the effect of suppressing the breakdown of fat in the adipose cells as well as numerous other functions, not all of which are well understood. (7)

In type I diabetes, which accounts for about five to ten percent of all cases, the pancreas fails to produce any insulin at all. The far more common type II diabetes is marked by cells’ resistance or insensitivity to insulin as well inadequate production of insulin. (1)The pancreas can sometimes compensate for cells’ reduced response to insulin by increasing secretion of the hormone, but when type II diabetes develops, such compensation fails, resulting in persistently high levels of blood glucose. Ultimately, untreated diabetes can lead to (among other things) blindness, kidney disease, nerve damage, cardiovascular disease and death. (1)

What causes insulin resistance is a hotly debated topic. Most researchers agree that a complicated mix of genetic and environmental factors is responsible. High blood glucose levels are an indication of insulin resistance, and they can also work to increase insulin resistance, a process called glucotoxicity. Which came first? (8)

Nor is it a simple matter to find an insulin-resistance gene. The pathway from insulin receptor to glucose-transport protein makes stops at several other proteins along the way, and any one could be the culprit. Immediately after the insulin receptor protein was identified, research focused on it and the gene that coded it as possible causes. Studies showed that the receptor was not usually the sole cause of insulin resistance, and many researchers focused on substrate molecules farther down the chain of reactions started by insulin. (9)But later experiments indicated that a complex interplay of the genes that code these proteins may be involved. Studies showed that mice who had inherited a faulty copy of the receptor gene from just one parent were not insulin resistant; neither were mice who had inherited a single copy of the gene that codes an important substrate in the reaction chain. But mice who had inherited one faulty copy of each gene did show a decreased sensitivity to insulin. (2)

Type II diabetes is generally characterized by both insulin resistance and a decrease in production of insulin by the beta cells of the pancreas. In 1999, a research group announced that it had tested the effect of insulin resistance on the very cells that produce insulin by turning off the receptor gene in the pancreas cells of mice. What resulted was a drop in insulin production – apparently, insulin receptors and the reactions they cause enable the beta cells to sense glucose and trigger the production of insulin. (10)

About a year ago, the same team genetically altered mice to turn insulin receptors in their brains – an organ in which insulin was once believed to have no role at all. The lack of insulin receptors in brain cells led to insulin resistance in other tissues – as well as increased appetite, weight gain and a 50 percent decrease in fertility. (3)

It seems clear, then, that obesity does not cause diabetes; no one factor does. The effects of insulin resistance in muscle and liver cells may work in an intricate feedback cycle with the effects of insulin resistance – and other factors influencing body weight -in the brain and in the pancreas.

One researcher claims to have found the thrifty gene, which allows the efficient storage of energy as fat during time of famine but results in deleterious obesity in times of plenty, among a group of Manitoba Indians. Although all persons with the gene developed diabetes by the age of 40, the thrifty gene can’t accurately be called the diabetes gene; the gene exists in only 40 percent of community members with diabetes.

Whatever environmental and behavioral factors contribute to diabetes, people who suffer from the disorder are likely to have a genetic predisposition to it and to obesity as well. It’s difficult enough to cope with diabetes without the added strain of finger-wagging doctors and disapproving public-health officials. There’s no scientific support for a scolding therapy.