a bio blog about genetics, genomics, and biotechnology
Posts Tagged ‘diabetes’
Josh: We must remember that not all inherited diseases are genetic in origin. Not only does the “genetic code”, the sequence of A, G, C, and T, matter but so do other modifications to that code. Examples are DNA methylation and histone modification.
A new study in the September issue of the Journal of Lipid Research suggests an unusual form of inheritance may have a role in the rising rate of diabetes, especially in children and young adults, in the United States.
DNA is the primary mechanism of inheritance; kids get half their genes from mom and half from dad. However, scientists are just starting to understand additional kinds of inheritance like metabolic programming, which occurs when an insult during a critical period of development, either in the womb or soon after birth, triggers permanent changes in metabolism.
In this study, the researchers looked at the effects of a diet high in saturated fat on mice and their offspring. As expected, they found that a high-fat diet induced type 2 diabetes in the adult mice and that this effect was reversed by stopping the diet.
However, if female mice continued a high-fat diet during pregnancy and/or suckling, their offspring also had a greater frequency of diabetes development, even though the offspring were given a moderate-fat diet. These mice were then mated with healthy mice, and the next generation offspring (grandchildren of the original high-fat fed generation) could develop diabetes as well.
In effect, exposing a fetal mouse to high levels of saturated fats can cause it and its offspring to acquire diabetes, even if the mouse goes off the high-fat diet and its young are never directly exposed.
The study used mice so it’s not time to warn women to eat differently during pregnancy and breastfeeding but earlier research has shown that this kind of inheritance is at work in humans. For example, there is an increased risk of hypertension and cardiovascular disease in children born of malnourished mothers.
Source: American Society for Biochemistry and Molecular Biology
“Effects of High Fat Diet Exposure During Fetal Life on Type 2 Diabetes Development in the Progeny”. Donatella Gniuli, Alessandra Calcagno, Maria Emiliana Caristo, Alessandra Mancuso, Veronica Macchi, Geltrude Mingrone, and Roberto Vettor. Journal of Lipid Research, Vol. 49, 1936-1945, September 2008
A Finnish study of identical twins has found that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy. The findings suggest that lifestyle, more than heredity, contributes to insulin resistance in people who are obese. Insulin resistance increases the chance of developing diabetes and heart disease.
The study, “Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity,” appears in the online edition of the American Journal of Physiology-Endocrinology and Metabolism, published by The American Physiological Society (www.the-aps.org).
The study was carried out by Linda Mustelin and Kirsi Pietiläinen, of Helsinki University Central Hospital and the University of Helsinki; Aila Rissanen, Anssi Sovijärvi and Päivi Piirilä of Helsinki University Central Hospital; Jussi Naukkarinen, Leena Peltonen and Jaakko Kaprio, University of Helsinki and National Public Health Institute; and Hannele Yki-Järvinen of Helsinki University Central Hospital and Minerva Medical Research Institute.
Environment can influence genes
Recent studies have suggested that defects in expression of genes involved in the body’s conversion of food to energy, known as mitochondrial oxidative phosphorylation, can lead to insulin resistance. The researchers wanted to know if defects in the expression of these genes are primarily a result of heredity or lifestyle. Because the twins in the study were identical, any differences that were found could be attributed to environmental factors, the researchers reasoned.
Twenty four pairs of identical twins, born in Finland between 1975 and 1979, took part in the study. Fourteen pairs (eight male and six female) were discordant for obesity, that is, one twin was obese, while the other was not. The control group consisted of five male and five female twin pairs who were concordant for weight. Some of the concordant pairs were normal-weight while some pairs were overweight.
The researchers measured whole body insulin sensitivity, body composition and cardiorespiratory fitness. They also obtained a needle biopsy of abdominal subcutaneous fat tissue, although they were unable to obtain this measurement for one of the discordant pairs.
Among the discordant pairs, the study found the obese twin had significantly lower:
- Insulin sensitivity, indicating the body has a harder time using glucose to produce energy.
- Fitness levels, as measured by maximum oxygen uptake and maximum work capacity.
- Transcription levels of genes that help cells convert food to energy (the genes of mitochondrial oxidative phosphorylation). Transcription is a multi-step process in which information in the genes is used to manufacture proteins. Proteins, in turn, direct cell activity. This suggests that the impaired expression of the genes may make it more difficult to lose excess weight, or may make additional weight gain more likely.
Heredity may still play role
“These data suggest that physical inactivity may have contributed to the defects in mitochondrial oxidative phosphorylation described in type 2 diabetic patients and prediabetic subjects,” the authors wrote. The authors also noted that, although environment plays a role in how these genes work, there still may be a hereditary component.
“Although we found that the reduced transcript levels of genes encoding mitochondrial oxidative phosphorylation in obesity is influenced by environmental and acquired factors, it does not exclude the possibility that genetic factors contribute to regulation of mitochondrial oxidative metabolism,” lead author Linda Mustelin noted.
The next step is to do a clinical study to see if exercise and other lifestyle changes can increase the expression of these genes.
Source: American Physiological Society
This is certainly possible, since so many things in our body are regulated by feedback mechanisms. Cells, and the body for that matter, are very adaptive. Take for example tolerance to drugs. Though, I’ve always assumed that insulin resistance was dietary more so than hereditary.
Unfortunately, the paper is not yet available.
Sun exposure and vitamin D levels may play a strong role in risk of type 1 diabetes in children, according to new findings by researchers at the Moores Cancer Center at University of California, San Diego (UCSD) and the Department of Family and Preventive Medicine. This association comes on the heels of similar research findings by this same group regarding vitamin D levels and several major cancers.
In this new study, the researchers found that populations living at or near the equator, where there is abundant sunshine (and ultraviolet B irradiance) have low incidence rates of type 1 diabetes. Conversely, populations at higher latitudes, where available sunlight is scarcer, have higher incidence rates. These findings add new support to the concept of a role of vitamin D in reducing risk of this disease.
Ultraviolet B (UVB) exposure triggers photosynthesis of vitamin D3 in the skin. This form of vitamin D also is available through diet and supplements.
“This is the first study, to our knowledge, to show that higher serum levels of vitamin D are associated with reduced incidence rates of type 1 diabetes worldwide,” said Cedric F. Garland, Dr. P.H., professor of Family and Preventive Medicine in the UCSD School of Medicine, and member of the Moores UCSD Cancer Center.
The study is published June 5 in the online version of the scientific journal Diabetologia.
Type 1 diabetes is the second most common chronic disease in children, second only to asthma. Every day, 1.5 million Americans deal with type 1 diabetes and its complications. About 15,000 new cases are diagnosed in the United States each year, where this disease is the main cause of blindness in young and middle-aged adults and is among the top reasons for kidney failure and transplants in youth and midlife.
“This research suggests that childhood type 1 diabetes may be preventable with a modest intake of vitamin D3 (1000 IU/day) for children, ideally with 5 to 10 minutes of sunlight around noontime, when good weather allows,” said Garland. “Infants less than a year old should not be given more than 400 IU per day without consulting a doctor. Hats and dark glasses are a good idea to wear when in the sun at any age, and can be used if the child will tolerate them.”
The association of UVB irradiance to incidence of type 1 diabetes remained strong even after the researchers accounted for per capita healthcare expenditure. This was an important consideration because regions located near the equator tend to have lower per capita healthcare expenditures, which could result in under-reporting of type 1 diabetes.
The researchers created a graph with a vertical axis for diabetes incidence rates, and a horizontal axis for latitude. The latitudes range from -60 for the southern hemisphere, to zero for the equator, to +70 for the northern hemisphere. They then plotted incidence rates for 51 regions according to latitude. The resulting chart was a parabolic curve that looks like a smile.
In the paper the researchers call for public health action to address widespread vitamin D inadequacy in U.S. children.
“This study presents strong epidemiological evidence to suggest that we may be able to prevent new cases of type 1 diabetes,” said Garland. “By preventing this disease, we would prevent its many devastating consequences.”
Source: University of California – San Diego
Licensed pesticide applicators who used chlorinated pesticides on more than 100 days in their lifetime were at greater risk of diabetes, according to researchers from the National Institutes of Health (NIH). The associations between specific pesticides and incident diabetes ranged from a 20 percent to a 200 percent increase in risk, said the scientists with the NIH’s National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI).
“The results suggest that pesticides may be a contributing factor for diabetes along with known risk factors such as obesity, lack of exercise and having a family history of diabetes,” said Dale Sandler, Ph.D., chief of the Epidemiology Branch at the NIEHS and co-author on the paper. “Although the amount of diabetes explained by pesticides is small, these new findings may extend beyond the pesticide applicators in the study,” Sandler said. Some of the pesticides used by these workers are used by the general population, though the strength and formulation may vary. Other insecticides in this study are no longer available on the market, however, these chemicals persist in the environment and measurable levels may still be detectable in the general population and in food products. For example, chlordane, which was used to treat homes for termites, has not been used since 1988, but can remain in treated homes for many decades. More than half of those studied in the National Health and Nutrition Examination Survey in 1999-2002 had measurable evidence of chlordane exposure. “This is not cause for alarm,” added Sandler “since there is no evidence of health effects at such very low levels of exposure.” … Continue Reading »
In an effort to understand how genes work, a collaborative study which includes the University of Southern California (USC) has identified a gene that regulates glucose levels. The results, which will be published in the July issue of the Journal of Clinical Investigation and is currently available online, may provide further understanding of the underlying causes of diabetes.
“Elevations of blood glucose are diagnostic of diabetes. This finding demonstrates there are gene variants that are important for day-to-day regulation of glucose, but they do not appear to play a significant role in disease risk,” says Richard M. Watanabe, Ph.D., associate professor of preventive medicine and physiology & biophysics at the Keck School of Medicine of USC and co-senior author of the paper. … Continue Reading »
An immune cell known as a neutrophil releases a protein that can suppress glucose production in the liver –without targeting insulin, researchers have found.
Neutrophils, a type of white blood cell, produce special immune proteins called defensins which seem to have a connection with glucose levels. During bacterial infection, defensin production can increase dramatically, a rise that frequently results in hypoglycemia. In addition, many patients with type II diabetes have decreased defensin levels. … Continue Reading »
Scientists have discovered a new technique for turning embryonic stem cells into insulin-producing pancreatic tissue in what could prove a significant breakthrough in the quest to find new treatments for diabetes.
The University of Manchester team, working with colleagues at the University of Sheffield, were able to genetically manipulate the stem cells so that they produced an important protein known as a ‘transcription factor’.
Stem cells have the ability to become any type of cell, so scientists believe they may hold the key to treating a number of diseases including Alzheimer’s, Parkinson’s and diabetes. … Continue Reading »
A comparison of two types of medications to treat type 2 diabetes finds that pioglitazone is more effective at lowering the rate of progression of plaque build-up in the coronary arteries than glimepiride, according to a study in the April 2 issue of JAMA. This study is being released early online March 31 to coincide with its presentation at the annual conference of the American College of Cardiology.
Atherosclerosis (process in which plaque builds up in the inner lining of the arteries) in patients with diabetes is particularly aggressive, characterized by higher cardiovascular event rates. Cardiovascular disease is the cause of death in approximately 75 percent of patients with diabetes. Determining the optimal treatment for coronary artery disease for patients with diabetes has important public health implications, according to information in the article. … Continue Reading »