A Cause of Insulin Resistance?
Source: American Diabetes Association
Publication date: 2003-05-16
Elderly people may develop insulin resistance -- one of the major risk factors for diabetes -- because "power plants" in their muscle cells decline or fail with age, according to Howard Hughes Medical Institute researchers at Yale University School of Medicine.
In studies of young and elderly people, the researchers found that older people had lower levels of metabolic activity in their mitochondria, the "factories" that provide power to cells. The findings suggest that reduced mitochondrial activity underlies insulin resistance, which is a major contributor to type 2 diabetes in the elderly.
{Anne-Marie- Mitochondria are cells that feed on glucose and burn fat in the muscle. If they are faulty they cannot do this as well as they should do. When people grow old they lose muscle mass but also the mitochondria become wasted due to inactvity. So they lose their function. Also in older people, they have lower anabolic hormones which improve muscle and help mitochondria to function. Now this effect on the mitchondria can be created artificially by both blocking androgen, and allowing muscles and mitchondria to waste. They cannot take glycogen in as they used to take it in before. So that excess glucose is converted to fat instead and stored. The muscles eventually waste much further and the more they waste, the less glycogen they can consume to burn as energy.}
In another recent study the researchers also found that physical activity can enhance the number of mitochondria in muscle by activation of a key enzyme called AMP kinase. "This is yet another reason for seniors to maintain an active lifestyle," said the study’s senior author, Gerald Shulman of the Howard Hughes Medical Institute at Yale. Shulman and his colleagues reported their findings in the May 16, 2003, issue of the journal Science.
According to Shulman, pinpointing the cause of type 2 diabetes in the elderly would help solve a major health problem. "Approximately one in four individuals over the age of 60 has type 2 diabetes, which is a remarkable statistic," said Shulman. "And, if you add impaired glucose tolerance, you’re talking about forty percent of the population."
The estimated economic burden of diabetes in United States is about $100 billion per year, a substantial proportion of which is due to diabetes in the elderly, said the researchers.
At the biochemical level, the hormone insulin promotes the transfer of glucose in the blood into cells for energy production and storage. Mitochondria within the cells convert glucose and fatty acids into energy via oxidation.
According to Shulman, previous studies in his laboratory had shown that insulin resistance in muscle and liver tissue can result from accumulation of fat and fatty acid metabolites.
"We hypothesized that there were two routes to this type of fat accumulation," said Shulman. "One is that the fat cells might release more fatty acids to be delivered to muscles and/or defects in mitochondrial oxidation might then lead to the accumulation of these fatty acids."
To trace the cause of insulin resistance in the elderly, the researchers compared glucose and fatty acid metabolism in matched groups of older and younger people. "One possibility is that as people age, they are less active and put on weight, and those factors are contributing to insulin resistance and diabetes," he said. "So a key aspect of this study is that our older and younger samples of people were matched for fat mass, lean body mass and physical activity habits." The sample groups consisted of 16 elderly volunteers, aged 61 to 84 years, and 13 younger volunteers, aged 18 to 39.
In initial metabolic tests of the effectiveness of insulin in the two groups, Shulman and his colleagues found significantly higher insulin resistance in the elderly subjects. They traced the insulin resistance to muscle tissue, using a non-radioactive "heavy" tracer isotope and techniques to measure insulin resistance.
The researchers next turned to nuclear magnetic resonance spectroscopy (NMR), to zero in on muscle cells to determine whether they were accumulating fat. In NMR spectroscopy, harmless magnetic fields and radio frequency pulses are used to detect and quantify signals characteristic of specific molecules. The NMR studies revealed that the elderly subjects showed much higher fat accumulation in their muscle cells.
"This finding is important because studies in our lab and others have shown that the amount of lipid inside the muscle cell is a very good predictor of insulin resistance," said Shulman.
Studies of the fat tissue in the elderly subjects showed that the fat cells were not releasing the extra fat that was accumulating in muscle. Thus, reasoned the researchers, the fatty molecules in the muscle cells might be accumulating due to defects in the cells’ fat-burning mitochondria.
Using NMR to follow chemicals labeled with non-radioactive tracer isotopes, the researchers could specifically measure the metabolism of fat in functioning mitochondria within the subjects’ muscle cells. Those studies revealed that, indeed, mitochondrial activity was reduced by about 40 percent in the cells of the elderly subjects, compared with the young.
Shulman theorizes that if the same mitochondrial defects occur in the insulin-producing cells of the pancreas, the progression from insulin resistance to diabetes will be complete.
Shulman said that before researchers can develop new clinical treatments to enhance mitochondrial function and thus help prevent diabetes, they must understand a great deal more about mitochondria. More basic research is needed to understand whether the number or individual activity of mitochondria are reduced in the elderly, as well as the role of mutations or other factors in such age-related reductions, he said.
"However, an encouraging note in this study is that -- since we’ve shown that exercise leads to more mitochondria by activation of AMP kinase -- by staying active, the elderly might well able to maintain mitochondrial content and head off such health problems," said Shulman. To test that possibility, the researchers also plan studies to compare mitochondrial activity in active and sedentary elderly people.
Here is some information about Type II diabetes. There are some serious side-effects that can occur and they do not and will not go away if they have cropped up or occured before they reverse the situation causing it. Heart disease, stroke, retinopathy (eye disease), kidney disease, skin problems that can become serious etc. I don’t think they should be scoffed at.
Type 2 Diabetes
Type 2 diabetes is the most common form of diabetes. In type 2 diabetes, either the body does not produce enough insulin or the cells ignore the insulin. Insulin is necessary for the body to be able to use sugar. Sugar is the basic fuel for the cells in the body, and insulin takes the sugar from the blood into the cells. When glucose builds up in the blood instead of going into cells, it can cause two problems:
- Right away, your cells may be starved of energy.
- Over time, high blood glucose levels may hurt your eyes, kidneys, nerves or heart.
Finding out you have diabetes is scary. But don’t panic! Diabetes is serious, but people with diabetes can live long, healthy, happy lives. You can too by taking good care of yourself.
There are many factors involved in controlling blood sugar levels, including diet, exercise and monitoring your blood sugar regularly. Controlling your diabetes is important to reduce the risk of long-term complications. At times, the disease can seem overwhelming. This section addresses various areas to help you live with type 2 diabetes.
A child with insulin resistance should be getting blood glucose checks done regularly at the very least.
Note: We are talking about a child on "normal every day" doses here only. I never went into what happens when he is stress dosed. When he is stressed dosed for illness, possibly higher blood sugars are the resulting dependaing how much the increase and whether it exceeds his real physiological needs which it is bound to do as we’re meant to err on the side of cautiion and give much more rather than not enough. As far as I am aware that could be more dangerous to him than just being on a steady every day dose due to the effect on blood sugar in the presence of yet the same androgen levels.
http://www.diabetes.org/main/application/commercewf?origin=*.jsp&event=link(D)