The incidence of type-2 diabetes is lower among women who get adequate calcium and supplement with vitamin D. Researchers used data from the Nurses Health Study, which includes over 83,000 women, to study the relationship of calcium and vitamin D intake to type-2 diabetes.
After 20 years of follow-up, it was concluded that a combined daily intake of over 1,200 mg of calcium and more than 800 IU of vitamin D was associated with a 33 percent lower risk of type-2 diabetes. Interestingly, dietary vitamin D intake did not appear to provide any statistically significant benefit. But the women who supplemented with at least 400 IU of vitamin D had a 13% lower risk of diabetes when compared to those who took less than 100 IU per day. Both dietary and supplemental calcium resulted in decreased risk of type-2 diabetes, and those with overall intakes above 1,200 mg had a 21% lower risk than those who got less than 600 mg per day. Elevated intakes of calcium and vitamin D, especially from supplements, are significantly associated with lower incidence of type-2 diabetes.
Source: Vitamin D and Calcium Intake in Relation to Type 2 Diabetes in Women, Anastassios G. Pittas et al, Diabetes Care 29:650-656, 2006
My recommendation: Active Calcium
Showing posts with label Type 2 Diabetes. Show all posts
Showing posts with label Type 2 Diabetes. Show all posts
Sunday, May 24, 2009
Monday, January 7, 2008
Cytokine Resistance Contributes To Pathology Of Type 2 Diabetes
ScienceDaily (Jun. 15, 2007) — In a study appearing this month in the Journal of Immunology, researchers at the University of Illinois describe how an impaired anti-inflammatory response plays a role in the pathology of type 2 diabetes.
Type 2 diabetes is classified as a metabolic disorder, but a growing number of researchers are beginning to think of it also as a disease of the innate immune system. Inflammation, a key component of the early immune response, is chronically elevated in people with type 2 diabetes. While the pro-inflammatory pathways of type 2 diabetes have received much attention, the anti-inflammatory side of the equation is less well known.
The new study focused on a number of cytokines, protein signals that bind to specific receptors on cells and set off a cascade of biochemical reactions within the cell. Interleukins, interferons, tumor necrosis factors and some growth factors are among the cytokines that direct many aspects of the immune response. Cytokines are secreted by many types of cells, including the immune cells known as macrophages.
In earlier studies, the researchers had shown that macrophages in diabetic and obese (diabese) mice secrete more pro-inflammatory and less anti-inflammatory cytokines than those of nondiabese mice. The team, led by pathology professor and department head Gregory Freund, also had demonstrated that human monocytes cultured under type 2 diabetic conditions had impaired interleukin-4 signaling. Interleukin 4 (IL-4) is an important player in the immune response in that it steers macrophages toward the production of other anti-inflammatory cytokines. It also inhibits secretion of the pro-inflammatory cytokines.
When IL-4 binds to its receptor on a target cell, it sets off one of two cascades of intracellular events.
The first of these signal transduction pathways, the Jak-STAT pathway, is well studied and well understood. The second, called the insulin receptor substrate 2 / phosphatidylinositol-3 kinase (IRS-2/PI3K) pathway, was more of a mystery, and of greater interest to Freund and his colleagues.
What drew them to this pathway was its potential role in the anti-inflammatory response, and its similarity to the cascade initiated when cells respond to insulin.
“One of the actions of diabetes is to create intracellular insulin resistance,” Freund said. “Some of the cytokines that work on cells share the same pathways as the insulin receptor.” Since diabetes causes insulin resistance, Freund said, “shouldn’t there be a resistance to cytokines, too? And that is what we found.”
The research team showed, for the first time, that the IRS-2 signaling arm of the interleukin-4 pathway directed the up-regulation of a key anti-inflammatory molecule in primary macrophages, and that this pathway was disrupted in type 2 diabetic conditions. They also showed that the loss of IL-4 function in diabese mice caused chronic over-expression of an important suppressor of cytokine signaling (SOCS) protein. This SOCS-3 protein aborts the cascade of events that normally leads to insulin uptake and/or cytokine signaling in a balanced inflammatory response.
This study supports earlier findings that inflammation is a key part of the pathology of diabetes, Freund said. Pro-inflammatory cytokines are elevated in type 2 diabetes, but the anti-inflammatory mechanisms are also impaired, leading to a multitude of major and minor health issues in the diabese.
“They get a cold. They get injured. Something happens. And it’s worse in those people with obesity or diabetes and lasts longer than it does in others,” Freund said. “Why? The imbalance may be the elevation in pro-inflammation. But it probably also includes a loss of anti-inflammatory function.”
This research was supported by grants from the National Institutes of Health, American Heart Association, and the
Adapted from materials provided by University of Illinois at Urbana-Champaign.
Pro-inflammatory Enzyme Linked To Diabetes; Immune System's Macrophages May Be Key To Treatment
ScienceDaily (Feb. 3, 2005 ) — An enzyme that initiates inflammation has been directly linked to insulin resistance and resulting type II diabetes by researchers at the UCSD School of Medicine. In addition, the team suggests that inhibition of the enzyme in the immune system’s macrophages may be a new diabetes therapy.
Published in the February 2005 issue of the journal Nature Medicine, the study describes research in mice that identifies enzyme IkB kinase ß (Ikk-ß) as a central coordinator of inflammatory responses in the liver and macrophages, the immune system cells which attack infections.
Both control mice and mice with Ikk-ß deleted in specific types of cells were fed a high-fat diet that normally causes metabolic syndrome and type II diabetes. While the control mice developed the diabetes and insulin-resistant symptoms, mice in which the Ikk-ß was deleted from microphages retained their healthy insulin levels.
“The potential for a new diabetes treatment is great,” said one of the study’s senior authors, Jerrold Olefsky, M.D., chief of UCSD’s Division of Endocrinology and Metabolism in the Department of Medicine, and associate dean for scientific affairs for the
Affecting 18.2 million Americans, diabetes is a disease in which the body does not produce or properly use insulin, a hormone necessary to convert sugar, starches and other food into energy needed for daily life. Previous studies in the past few years have implicated inflammation as playing a role in diabetes, but just how this occurred was unknown.
The researchers generated mice without Ikk-ß in liver cells that play a direct role in insulin-regulated glucose metabolism, and in systemic myeloid cells, pivotal players in inflammatory responses as they produce macrophages.
In response to challenges with a high-fat diet, mice with Ikk-ß deficient myeloid cells retained insulin sensitivity in all target tissues. Because the myeloid cells (and their macrophages) are systemic – able to travel throughout the body – they were identified by the researchers as the best target for diabetes treatments.
The mice lacking Ikk-ß only in the liver retained their insulin sensitivity in the liver but became insulin resistant in fat and muscle. Other tissue, such as muscle, was not tested in this study, because a previous study has shown that deletion of Ikk-ß in muscle has no effect on obesity-induced insulin resistance and type II diabetes, although muscle is a major insulin-responsive tissue.
In addition to Olefsky, a senior author of the paper was Michael Karin, Ph.D., UCSD professor of pharmacology, an American Cancer Society Research Professor, and the scientist who first discovered IKK and its subunits. The paper was a collaborative effort between the diabetes lab of Olefsky and Karin’s molecular signaling lab in the department of pharmacology.
Additional authors included first author Melek C. Arkan, UCSD Department of Pharmacology; and Andrea L. Hevener, UCSD Division of Endocrinology and Metabolism, Department of Medicine; Florian R. Freten, Shin Maeda, Zhi-Wei Li, UCSD Division of Endocrinology and Metabolism, Department of Medicine; Jeffrey M. Long, Ph.D., and Anthony Wynshaw-Boris, M.D., Ph.D., UCSD Departments of Pediatrics and Medicine; and Giuseppe Poli, S. Luigi Hospital, University of Turin, Italy. The study was funded by the National Institutes of Health.
Adapted from materials provided by University Of California - San Diego.
Type 2 Diabetes: Inflammation, Not Obesity, Cause Of Insulin Resistance
ScienceDaily (Nov. 7, 2007) — Researchers at the University of California, San Diego (UCSD) School of Medicine have discovered that inflammation provoked by immune cells called macrophages leads to insulin resistance and Type 2 diabetes. Their discovery may pave the way to novel drug development to fight the epidemic of Type 2 diabetes associated with obesity, the most prevalent metabolic disease worldwide.
In recent years, it has been theorized that chronic, low-grade tissue inflammation related to obesity contributes to insulin resistance, the major cause of Type 2 diabetes. In research done in mouse models, the UCSD scientists proved that, by disabling the macrophage inflammatory pathway, insulin resistance and the resultant Type 2 diabetes can be prevented.
In recent years, it has been theorized that chronic, low-grade tissue inflammation related to obesity contributes to insulin resistance, the major cause of Type 2 diabetes. In research done in mouse models, the UCSD scientists proved that, by disabling the macrophage inflammatory pathway, insulin resistance and the resultant Type 2 diabetes can be prevented.
The findings of the research team, led by principle investigators Michael Karin, Ph.D., Professor of Pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, and Jerrold Olefsky, Distinguished Professor of Medicine and Associate Dean for Scientific Affairs, will be published as the feature article of the November 7 issue of Cell Metabolism.
"Our research shows that insulin resistance can be disassociated from the increase in body fat associated with obesity," said Olefsky.
Macrophages, found in white blood cells in the bone marrow, are key players in the immune response. When these immune cells get into tissues, such as adipose (fat) or liver tissue, they release cytokines, which are chemical messenger molecules used by immune and nerve cells to communicate. These cytokines cause the neighboring liver, muscle or fat cells to become insulin resistant, which in turn can lead to Type 2 diabetes.
The UCSD research team showed that the macrophage is the cause of this cascade of events by knocking out a key component of the inflammatory pathway in the macrophage, JNK1, in a mouse model. This was done through a procedure called adoptive bone marrow transfer, which resulted in the knockout of JNK1 in cells derived from the bone marrow, including macrophages.
With this procedure, bone marrow was transplanted from a global JNK1 knockout mouse (lacking JNK1 in all cell types) into a normal mouse that had been irradiated to kill off its endogenous bone marrow. This resulted in a chimeric mouse in which all tissues were normal except the bone marrow, which is where macrophages originate. As a control, the scientists used normal, wild-type mice as well as mice lacking JNK1 in all cell types. These control mice were also subjected to irradiation and bone marrow transfer.
The mice were all fed a high-fat diet. In regular, wild-type mice, this diet would normally result in obesity, leading to inflammation, insulin resistance and mild Type 2 diabetes. The chimeric mice, lacking JNK1 in bone marrow-derived cells, did become obese; however, they showed a striking absence of insulin resistance -- a pre-condition that can lead to development of Type 2 diabetes.
"If we can block or disarm this macrophage inflammatory pathway in humans, we could interrupt the cascade that leads to insulin resistance and diabetes," said Olefsky. "A small molecule compound to block JNK1 could prove a potent insulin-sensitizing, anti-diabetic agent."
The research also proved that obesity without inflammation does not result in insulin resistance. Olefsky explained that when an animal or a human being becomes obese, they develop steatosis, or increased fat in the liver. The steatosis leads to liver inflammation and hepatic insulin resistance.
The chimeric mice did develop fatty livers, but not inflammation. "Their livers remained normal in terms of insulin sensitivity," said Olefsky, adding that this shows that insulin resistance can also be disassociated from fatty liver.
"We aren't suggesting that obesity is healthy, but indications are promising that, by blocking the macrophage pathway, scientists may find a way to prevent the Type 2 diabetes now linked to obesity and fatty livers," Olefsky said.
Co-first authors of the paper are Giovanni Solinas, UCSD Department of Pharmacology and Cristian Vilcu, UCSD Division of Endocrinology and Metabolism.
Additional contributors include Jun-Li Luo, Willscott Naugler and Sergei Grivennikov, UCSD Department of Pharmacology; Jaap G. Neels, and Gautam K. Bandyopadhyay, UCSD Division of Endocrinology and Metabolism; Anthony Wynshaw-Boris, UCSD Departments of Pediatrics and Medicine; and Miriam Scadeng, UCSD Department of Radiology.
This research was supported by National Institutes of Health grants ES004151, ES006376, DK033651 and DK074868. Additional funding was provided by a fellowship from the Swiss National Science Foundation, a University of California Discovery Grant and Mentor-Based Postdoctoral Fellowships from the American Diabetes Association.
Adapted from materials provided by University of California - San Diego.
University of California - San Diego (2007, November 7). Type 2 Diabetes: Inflammation, Not Obesity, Cause Of Insulin Resistance. ScienceDaily. Retrieved January 8, 2008, from http://www.sciencedaily.com /releases/2007/11/071106133106.htm
Diabetes, Depression Together Increase Risk For Heart Patients
ScienceDaily (Mar. 11, 2007 ) — Having both depression and type 2 diabetes increases the risk of death for heart patients. Each factor had been known to increase the risk of heart disease deaths by itself, but together they're even more deadly.
In an analysis of more than 900 patients with established coronary artery disease,
The study showed that among type 2 diabetes patients, having high depression scores increased the risk of dying by 20 to 30 percent compared to patients with similar depression scores but no type 2 diabetes.
"We found a trend showing that the probability of death increases as the level of depression increases in diabetic patients with coronary artery disease," said Duke researcher Anastasia Georgiades, Ph.D. "Our data appear to show an important interaction between type 2 diabetes and depression, meaning that physicians should closely monitor their heart patients who have both of these disorders."
"There is some sort of synergistic effect between type 2 diabetes and depression that we don't fully understand," Georgiades said. "In our analysis, we controlled for factors that could influence mortality, such as heart disease severity and age. For whatever reasons, these patients were still at higher risk of dying, and future research will aim to investigate the mechanisms for this association."
The research was supported by the National Heart, Lung, Blood Institute.
The researchers followed 933 heart patients for more than four years and correlated the 135 deaths that occurred during that period with the presence of type 2 diabetes and depression alone and together.
Georgiades said there are some possible explanations for the link between depression and diabetes.
"Patients with type 2 diabetes typically have an extensive self-care regimen involving special diet, medications, exercise and numerous appointments with their doctor," she said. "It may be that such patients who are depressed might not be as motivated to carry out all these activities, thereby putting them at higher risk."
Depression has also been linked to other cardiovascular risk factors such as insulin resistance, hypertension, obesity, increased cigarette smoking, alcohol abuse and physical inactivity.
Adapted from materials provided by Duke University Medical Center.
New Study Confirms Diabetics Face Significantly Higher Risks Of Colorectal Cancer
ScienceDaily (Nov. 1, 2005 ) — A new study confirms that patients with diabetes are significantly more likely to have colon cancer than individuals without diabetes. Researchers at the Medical University of South Carolina reported results from a large cross-sectional analysis assessing the risk of colon cancer among patients with diabetes at the 70th Annual Scientific Meeting of the American College
Researchers analyzed data from a comprehensive nationally representative sample of patients using the 1997-2003 National Health Interview Survey. Of the 226,953 patients in the study, 5.9 percent had a history of diabetes. Researchers controlled for age, race, gender, obesity, alcohol use, tobacco use, and physical activity. Adjusting for potentially confounding factors, researchers found that people with diabetes were 1.4 times more likely to have colon cancer as individuals without diabetes.
"This work is important because it suggests that people with diabetes may be at higher risk of colon cancer. Until we know for sure, diabetics should pay particular attention to their doctor's recommendations for colorectal screening," said Donald Garrow, M.D. one of the investigators.
Adapted from materials provided by American College of Gastroenterology.
Scientists Discover Connection Between Obesity And Diabetes
ScienceDaily (Dec. 15, 2003) — DENVER (December 11, 2003) -- Scientists with the Eleanor Roosevelt Institute at the University of Denver have made a revolutionary discovery that for the first time establishes a biochemical connection between obesity and Type 2 Diabetes. This study was published in this month's Journal of Endocrinology.
Type 2 Diabetes occurs when the body either doesn't make enough insulin or becomes resistant to insulin, preventing it from storing sugar thus increasing the body's sugar levels to beyond what is normal and healthy. In the
In this landmark study, tests in mice found that diabetes in obese mice requires a hormone known as MSH, which is made by the POMC gene that is found in both mice and humans. The study found that obese mice without the MSH hormone were obese but did not develop diabetes. Administration of the MSH hormone to these mice increased resistance to insulin and directly affected blood sugar levels. Therefore, MSH may be a factor in the development of Type 2 Diabetes.
"Our findings show that obese people with high levels of the hormone MSH may be more likely to be diabetic than obese people with low levels of the MSH hormone," explained the study's lead author Miles B. Brennan, Ph.D., and ERI scientist. "While we knew that there was a connection between obesity and diabetes, this is the first time that the link between the hormone MSH and blood sugar levels has been established."
According to Brennan, this study will possibly lead to more preventive treatments for diabetes. Preventive treatments, such as testing the MSH hormone levels in obese individuals and then administering a medication if the levels are too high, are currently being studied.
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Adapted from materials provided by Eleanor Roosevelt Institute.
Sunday, January 6, 2008
Risk Of Stroke Doubles If Diagnosed With Type 2 Diabetes
ScienceDaily (Jun. 15, 2007) — Individuals diagnosed with Type 2 diabetes are at double the risk of having a stroke compared to those without diabetes, according to new research from the University of Alberta. It was found that the risk of a stroke is considered high within the first five years of treatment for Type 2 diabetes and more than doubles the rate of occurrence.
For this study, the researchers entered 12,272 subjects into a Type 2 diabetes cohort. All subjects were recently diagnosed with Type 2 diabetes and had a mean age of 64 years. After five years of monitoring, stroke incidence rates were compared between the cohort and the general population.
"What we found is that 9.1 per cent of the diabetes cohort had a stroke within the first five years of their diagnosis," Dr. Thomas Jeerakathil, an assistant professor in neurology, at the
As it has been more common to study stroke prevalence within 10 years after diagnosis, this is the first study to specifically examine stroke-related outcomes immediately after the diagnosis of and initiation of treatment for Type 2 diabetes.
Jeerakathil indicates it is possible that physicians are undertreating stroke risks because of a prevailing attitude among physicians and patients that the cardiovascular complications of diabetes occur long after diagnosis rather than in the first five years.
"We hope our findings will help to dispel the notion that the risk of stroke occurs only in the long term and will improve the motivation of both patients and health care providers to aggressively control cardiovascular risk factors soon after diagnosis." said Jeerakathil.
The research recently appeared in the American Heart Association's Stroke journal.
Adapted from materials provided by University of Alberta.
Low Glycemic Index Diet Best For Weight Loss And Cardiovascular Health
ScienceDaily (Jul. 26, 2006) — The most effective diet for weight loss and cardiovascular health is a high carbohydrate plan based on low glycemic index (GI) foods, according to a study by University of Sydney researchers.
Published in the most recent issue of Archives of Internal Medicine, the world's first 12 week parallelled, randomised, controlled trial compared the relative effects on weight loss and cardiovascular risk of low GI and high-protein diets.
Undertaken by Professor Jennie Brand-Miller and Joanna McMillan-Price from the University of Sydney Human Nutrition Unit, the findings show that there is no 'one diet fits all' solution, and although both high protein and low GI diets will help you to shed fat. However, it did show that a diet containing low GI carbohydrate significantly reduces your risk of heart disease.
The trial, which was led by Joanna McMillan-Price, enrolled 129 overweight or obese young adults (aged 18-40 years) and randomly assigned them to one of four reduced calorie, reduced fat diets over a 12 week period. Two of the diets were high-carbohydrate diets and the other two high in protein - one of each had a high GI and the other had a low GI.
Between the two high-carbohydrate diets, lowering the glycemic index doubled fat loss - this effect was strongest in women. Participants on the high-protein, high GI diet was equally effective for fat loss as the high carbohydrate, low GI diet, the two had diverse effects on LDL (bad) cholesterol - the high protein, high-GI group showed increased levels of LDL or 'bad' cholesterol, while there were significant reductions in those on the high carbohydrate, low-GI diet. However those on the high-protein, low GI diet did not experience the same rise in total LDL cholesterol suggesting the importance of low GI foods alongside a high meat intake.
"Our findings suggest that dietary glycemic load, and not just overall energy intake influences weight loss and postprandial glycaemia (blood sugar levels after eating)," said Joanna McMillan-Price.
"We found that moderate reductions in glycemic load appear to increase the rate of body fat loss, particularly in women. Diets based on low-glycemic index, whole grain products, tend to be better for the heart, maximising cardiovascular risk reduction - particularly if protein intake is high," said Joanna McMillan-Price.
Adapted from materials provided by University Of Sydney.
High-glycemic Index Carbohydrates Associated With Risk For Developing Type 2 Diabetes In Women
ScienceDaily (Nov. 27, 2007) — Eating foods high on the glycemic index, which measures the effect of carbohydrates on blood glucose levels, may be associated with the risk for developing type 2 diabetes in Chinese women and in African-American women, according to two new studies. However, eating more cereal fiber may be associated with a reduced risk for type 2 diabetes in African-American women.
Researchers remain uncertain regarding exactly how diet, including carbohydrate intake, affects the development of type 2 diabetes, according to background information in the articles. Studies have revealed that the body absorbs carbohydrates from different foods at different rates. This leads to varying effects on levels of blood glucose and the hormone insulin, which converts glucose into energy.
Foods high on the glycemic index, such as rice and other simple carbohydrates, cause a rapid spike and then a drop in blood glucose, whereas high-fiber foods tend to be lower on the glycemic index and have a more gradual effect. Some evidence has linked high--glycemic index foods with the risk of developing type 2 diabetes.
In one study, Supriya Krishnan, D.Sc., of Boston University School of Public Health, and colleagues examined data from 40,078
During eight years of follow-up, 1,938 participants developed type 2 diabetes. Women who ate high--glycemic index foods or a diet with a high glycemic load had a higher risk for diabetes. However, women who ate more fiber from grains (cereal fiber) had a reduced risk; for women with a body mass index (BMI) of less than 25, women who ate about 1.5 grams of fiber per day were 59 percent less likely to develop diabetes than women who ate about 8.3 grams per day.
Because high--glycemic index foods increase blood glucose levels significantly, they increase the body's demand for insulin, the authors note. This can contribute to problems with the pancreas (which produces insulin) that may eventually lead to diabetes. In addition, high--glycemic index foods can directly decrease the body's response to insulin by increasing the production of fatty acids after meals.
"Our results indicate that black women can reduce their risk of diabetes by eating a diet that is high in cereal fiber," the authors write. "Incorporating fiber sources into the diet is relatively easy: a simple change from white bread (two slices provides 1.2 grams of fiber) to whole wheat bread (two slices provides 3.8 grams of fiber) or substituting a cup of raisin bran (5 to 8 grams of fiber) or oatmeal (4 grams of fiber) for a cup of corn chex (0.5 grams of fiber) or rice chex (0.3 grams of fiber) will move a person from a low fiber intake category to a moderate intake category, with a corresponding 10 percent reduction in risk."
In another study, Raquel Villegas, Ph.D., of
During the study, 1,608 of the women developed diabetes. Women who consumed more carbohydrates overall were more likely to develop diabetes--when they were split into five groups based on carbohydrate intake, those in the group consuming the most (about 337.6 grams per day) had a 28 percent higher risk than those in the group consuming the least (about 263.5 grams per day). Women who ate diets with a higher glycemic index and who ate more staples such as bread, noodles and rice specifically also had an increased risk. Women who ate 300 grams or more of rice per day were 78 percent more likely to develop diabetes than those who ate less than 200 grams per day.
"Given that a large part of the world's population consumes rice and carbohydrates as the mainstay of their diets, these prospective data linking intake of refined carbohydrates to increased risk of type 2 diabetes mellitus may have substantial implications for public health," the authors conclude.
Journal reference: Arch Intern Med. 2007;167(21):2304-2309, 2310-2316.
Adapted from materials provided by JAMA and Archives Journals.
Exercise Pivotal In Preventing And Fighting Type II Diabetes
ScienceDaily (Feb. 9, 2007) — One in three American children born in 2000 will develop type II diabetes, according to the U.S. Centers for Disease Control and Prevention (CDC). A new study at the University of Missouri-Columbia says that acute exercise - as little as 15 minutes a day - can have a profound influence on preventing and fighting the disease.
This research adds to the body of evidence that indicates exercise can fight type II diabetes, one of the most widespread self-inflicted healthcare struggles in the
"Many people can fight type II diabetes through diet and exercise alone," said John Thyfault, professor in the MU
Type II diabetes results from a lack of insulin production and insulin resistance in skeletal muscle cells. Insulin is necessary to help drive glucose out of the blood and into the tissues of the body. As a result of insulin resistance, cells do not respond appropriately to insulin, causing more insulin to be released to have a measurable effect and ultimately causing insulin and glucose to build up dangerously in the blood.
Thyfault's study found that relatively short periods of acute muscle exercise in diabetic Zucker rats significantly increased insulin sensitivity in the previously insulin resistance skeletal muscles. Since 80 to 90 percent of all glucose goes into muscle after a meal, it is reasonable that more active muscles on a day- to-day basis will result in increased insulin sensitivity, Thyfault said.
"In relation to a person with type II diabetes, this would mean that they could lessen their dependence on insulin therapy to control their blood glucose levels or potentially control glucose levels without any drug by just increasing their daily activity levels in addition to the right diet," Thyfault said.
The study, "Contraction of insulin resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism," will be published in the American Journal of Physiology-Cell.
Adapted from materials provided by University of Missouri-Columbia.
Rate Of Cellular Energy Production Lower In Persons At Risk For Type 2 Diabetes
ScienceDaily (Aug. 26, 2005) — New Haven, Conn.-The rate of insulin-stimulated energy production is significantly reduced in the muscles of lean, healthy young adults who have already developed insulin resistance and are at increased risk of developing diabetes later in life, according to a Yale School of Medicine study.
The new research by Gerald Shulman, M.D., professor of internal medicine, endocrinology, and senior author of the study, indicates that a decreased ability to burn sugars and fats efficiently is an early and central part of the diabetes problem. The new data also suggest that the basic defect lies within the mitochondria, which are the energy factories inside cells that produce most of the chemical power needed to sustain life.
The young adults studied by the research team are the offspring of parents who have type 2 diabetes, adding support to the idea that the risk can be inherited and that the problem begins well before diabetes symptoms become evident. The researchers observed that the mitochondria in the subjects' muscle cells responded poorly to insulin stimulation. Normal mitochondria react to insulin by boosting production of an energy-carrying molecule, ATP, by 90 percent. But the mitochondria from the insulin-resistant people they tested only boosted ATP production by five percent.
Among their findings was also evidence for a severe reduction in the amount of insulin stimulated phosphorus transport into the muscle cells of the insulin-resistant participants. This also points to a dramatic defect in insulin signaling and may explain the observed abnormalities in insulin-stimulated power production in the insulin-resistant study subjects. Phosphorus is a key element in the mithochondrion's complex energy-production process.
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The co-authors were Kitt Petersen and Sylvie Dufour.
PLoS Medicine 2: www.plosmedicine.org (September 2005)
Adapted from materials provided by Yale University.
Lots Of Low-fat Food Is Better Than Small Portions Of High-fat Food
ScienceDaily (Feb. 6, 2004 ) — Dutch research has shown that a diet of low-fat products is better than smaller portions of normal high-fat food for preventing diabetes in obese people. Mice put on a low-fat diet were more sensitive to insulin than mice that received the same amount of energy in the form of high-fat food.
Martin Muurling put obese mice on different diets in which the total energy intake and the final body weight were the same. He then studied the effect of these diets on insulin sensitivity.
Mice that received just low-fat products were more sensitive to insulin than mice that ate small portions of high fat food. A low-fat diet is, therefore, a more effective remedy for diabetes than eating less calories.
Muurling also discovered that in mice, the consumption of fish oil had no positive effects whatsoever on reduced insulin sensitivity. From this he concluded that a diet with fish oil cannot prevent or remedy diabetes in the case of somebody who is already less sensitive to insulin due to a high-fat diet.
Clinically obese people sometimes suffer from a certain form of diabetes, type II diabetes mellitus. This is because far more fatty acids are released from the adipose tissue during obesity. These fatty acids can reduce the functioning of the beta cells in the pancreas as well as the sensitivity of various tissues to insulin.
Fat accumulation in adipose tissue is less harmful than fat accumulation in organs such as the liver and muscles. Treatment methods that lead to a reduction of fat accumulation in the liver and muscles might also remedy type II diabetes mellitus in obese patients.
In diabetics, the regulation of the blood glucose level and the transport of glucose from the blood to tissue cells are disrupted. This is due to either an inadequate production of insulin or the insulin available not being effective enough. Obesity and type II diabetes mellitus will probably be the health problems of the 21st century, as the number of obese people has risen sharply over the last few decades.
The research was funded by the Netherlands Organisation for Scientific Research.
Adapted from materials provided by Netherlands Organization For Scientific Research.
Type 2 Diabetes
Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non-insulin-dependent diabetes (NIDDM), obesity-related diabetes, or adult-onset diabetes) is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency and hyperglycemia. It is often managed by engaging in exercise and modifying one's diet. It is rapidly increasing in the developed world, and there is some evidence that this pattern will be followed in much of the rest of the world in coming years. The CDC has characterized the increase as an epidemic.[1] In addition, whereas this disease used to be seen primarily in adults over age 45, in contrast to Diabetes mellitus type 1, it is now increasingly seen in children and adolescents, an increase thought to be linked to rising rates of obesity in this age group. [2]
Unlike Type 1 diabetes, there is little tendency toward ketoacidosis in Type 2 diabetes, though it is not unknown. One effect that can occur is nonketonic hyperglycemia which also quite dangerous, though it must be treated very differently. Complex and multifactorial metabolic changes very often lead to damage and function impairment of many organs, most importantly the cardiovascular system in both types. This leads to substantially increased morbidity and mortality in both Type 1 and Type 2 patients, but the two have quite different origins and treatments despite the similarity in complications.
Pathophysiology
Insulin resistance means that body cells do not respond appropriately when insulin is present.
Other important contributing factors:
- increased hepatic glucose production (e.g., from glycogen degradation), especially at inappropriate times
- decreased insulin-mediated glucose transport in (primarily) muscle and adipose tissues (receptor and post-receptor defects)
- impaired beta-cell function—loss of early phase of insulin release in response to hyperglycemic stimuli
- Cancer survivors who received allogenic Hematopoietic Cell Transplantation (HCT) are 3.65 times more likely to report type 2 diabetes than their siblings. Total body irradiation (TBI) is also associated with a higher risk of developing diabetes.
Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. However, severe complications can result from improperly managed Type 2 diabetes, including renal failure, blindness, wounds that are slow to heal (including surgical incision), and arterial disease, including coronary artery disease. The onset of Type 2 is most common in middle age and later life, though a form of it, called MODY is being much more frequently seen in adolescents.
Diabetes mellitus type 2 is presently of unknown etiology (i.e., origin). Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus. Examples include diabetes mellitus caused by hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g. long-term steroid use).
About 90–95% of all North American cases of diabetes are type 2[3], and about 20% of the population over the age of 65 has diabetes mellitus type 2. The fraction of type 2 diabetics in other parts of the world varies substantially, almost certainly for environmental and lifestyle reasons, though these are not known in detail. Diabetes affects over 150 million people worldwide and this number is expected to double by 2025[3]. There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 increases risks of developing type 2 diabetes very substantially. In addition there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes[4],[5]. About 55 percent of type 2 are obese[6] —chronic obesity leads to increased insulin resistance that can develop into diabetes, most likely because adipose tissue is a (recently identified) source of several chemical signals to other tissues (hormones and cytokines). Other research shows that type 2 diabetes causes obesity.[7]
Diabetes mellitus type 2 is often associated with obesity, hypertension, elevated cholesterol (combined hyperlipidemia), and with the condition often termed Metabolic syndrome (it is also known as Syndrome X, Reavan's syndrome, or CHAOS). It is also associated with acromegaly, Cushing's syndrome and a number of other endocrinological disorders. Additional factors found to increase risk of type 2 diabetes include aging[8], high-fat diets[9] and a less active lifestyle[10].
From Wikipedia, the free encyclopedia
Insufficient Sleep Raises Risk Of Diabetes, Study Suggests
ScienceDaily (Dec. 2, 2007 ) — The most common factors believed to contribute to diabetes are a decreased amount of physical activity and access to highly palatable processed foods. However, there is growing evidence that another aspect of our modern lifestyle, short sleep duration, is also contributing toward the "diabetes epidemic", according to a new study.
The study, authored by James E. Gangwisch, PhD, of
According to the results, subjects who reported sleeping five or fewer hours and subjects who reported sleeping nine or more hours were significantly more likely to have incident diabetes over the follow-up period than were subjects who reported sleeping seven hours, even after adjusting for variables such as physical activity, depression, alcohol consumption, ethnicity, education, marital status, age, obesity and history of hypertension.
The effect of short sleep duration on diabetes incidence is likely to be related in part to the influence of short sleep duration upon body weight and hypertension, said Dr. Gangwisch. Experimental studies have shown sleep deprivation to decrease glucose tolerance and compromise insulin sensitivity by increasing sympathietic nervous system activity, raising evening cortisol levels and decreasing cerebral glucose utilization. The increased burden on the pancreas from insulin resistance can, over time, compromise â-cell function and lead to type two diabetes, warned Dr. Gangwisch.
"If short sleep duration functions to increase insulin resistance and decrease glucose tolerance, then interventions that increase the amount and improve the quality of sleep could potentially serve as treatments and as primary preventative measures for diabetes," said Dr. Gangwisch.
It is unknown as to how long sleep duration contributes to diabetes, although increased time in bed to compensate for poor sleep quality is one possible explanation, noted Dr. Gangwisch.
Recent estimates show that at least 171 million people worldwide suffer from diabetes, and that, by the year 2030, this number is projected to double.
Lawrence Epstein, MD, medical director of Sleep HealthCenters, an instructor of medicine at Harvard Medical School, a past president of the American Academy of Sleep Medicine (AASM) and a member of the AASM board of directors, said that this study is one of several large studies that have shown that people who don't get enough sleep have higher rates of diabetes.
"Restricting sleep to four hours a night for only a few days causes abnormal glucose metabolism, suggesting the mechanism for increased rates of diabetes in sleep deprived individuals," said Dr. Epstein. "Additionally, sleep disorders that disrupt sleep, such as obstructive sleep apnea, also increase the likelihood of developing diabetes. Treating the sleep disorders improves glucose metabolism and diabetes control. These studies underscore the fact that sleep is integral to good health."
On average, most adults need seven to eight hours of sleep each night to feel alert and well-rested. Adolescents should sleep about nine hours a night, school-aged children between 10-11 hours a night and children in pre-school between 11-13 hours a night.
The article, "Sleep Duration as a Risk Factor for Diabetes Incidence in a Large U.S. Sample", is published in the December 1 issue of the journal Sleep.
Study Adds To Links Between Sleep Loss And Diabetes
ScienceDaily (Sep. 19, 2006) — Short or poor quality sleep is associated with reduced control of blood-sugar levels in African Americans with diabetes, report researchers from the University of Chicago in the Sept. 18, 2006, issue of the Archives of Internal Medicine.
The finding suggests that one inexpensive way to improve the health of patients with type 2 diabetes might be to improve the duration and quality of their sleep.
"Sleep is modifiable," said Kristen Knutson, research associate (assistant professor) in the department of health studies at the
"Although we can't be certain whether sleep loss makes diabetes worse or the diabetes interferes with sleep, it only makes sense for everyone, but especially patients with diabetes, to give themselves the opportunity to get enough sleep," Knutson said.
The study focused on 161 African-American patients being treated at the University of Chicago Hospitals for type 2 diabetes. The researchers asked participants how much sleep they thought they needed at night and how much sleep they managed to get on weeknights and weekends. They also assessed the quality of their sleep using a standard 19-item questionnaire, the Pittsburgh Sleep Quality Index (PSQI).
To assess blood sugar control they measured glycosylated hemoglobin, a standard tool for management of patients with diabetes. Glycosylated hemoglobin, or HbA1c, reflects the average blood glucose level over the previous three months. A normal HbA1c result is between four and six percent. Higher levels represent poor glucose control. Patients with diabetes are considered to be under good control if they can keep their levels below seven percent.
The researchers found that, on average, the 161 diabetes patients got very little sleep and had poor glucose control. Mean sleep duration was six hours a night. Only six percent reported getting eight hours of sleep on weeknights and only 22 percent reported getting at least seven hours. Seventy-one percent had poor sleep quality. The median HbA1c score was 8.3 percent.
Many patients with diabetes have painful complications that can interfere with sleep. Even after the researchers excluded 39 patients who reported such pain, however, two out of three of the remaining 122 patients reported poor quality sleep. The average HbA1c among those patients was almost as high: 8.2 percent.
Insufficient or poor quality sleep was closely associated with higher HbA1c results. For patients with no complications of their diabetes, a three-hour "perceived sleep debt"--the difference between how much sleep they felt they needed and how much they think they got--was associated with a 1.1 percentage-point increase in HbA1c levels, for example from 7.5 percent up to 8.6 percent.
For patients with at least one complication of diabetes--such as nerve pain, kidney damage or coronary artery disease--decreased sleep quality appeared to be more important. An increase of five points (out of 21) on the PSQI was associated with a 1.9 percentage-point increase in HbA1c, for example from 8.7 percent up to 10.6 percent.
"The magnitude of these effects," the authors note, "is comparable to those of widely used oral antidiabetic agents."
A long series of laboratory and epidemiologic studies has suggested that cutting back on sleep has a harmful effect on glucose control, insulin secretion and metabolism in ways that might increase diabetes risk, said Eve Van Cauter, professor of medicine at the
"Our findings suggest, at least in this study population, that short or poor sleep is associated with decreased blood-sugar control in patients who already have diabetes," she said. "The growing tendency to burn the candle at both ends may be a significant contributor to the current epidemic of diabetes. One way to slow down this epidemic may be to avoid building a chronic sleep debt."
The MacArthur Foundation, the American Diabetes Association and the National Institutes of Health funded this study. Additional authors are Armand Ryden, of the University of Chicago, and Bryce Mander, now at
Adapted from materials provided by University of Chicago Medical Center.
Lack Of Deep Sleep May Increase Risk Of Type 2 Diabetes
ScienceDaily (Jan. 2, 2008) — Suppression of slow-wave sleep in healthy young adults significantly decreases their ability to regulate blood-sugar levels and increases the risk of type 2 diabetes, report researchers at the University of Chicago Medical Center.
Deep sleep, also called "slow-wave sleep," is thought to be the most restorative sleep stage, but its significance for physical well-being has not been demonstrated. This study found that after only three nights of selective slow-wave sleep suppression, young healthy subjects became less sensitive to insulin. Although they needed more insulin to dispose of the same amount of glucose, their insulin secretion did not increase to compensate for the reduced sensitivity, resulting in reduced tolerance to glucose and increased risk for type 2 diabetes. The decrease in insulin sensitivity was comparable to that caused by gaining 20 to 30 pounds.
Previous studies have demonstrated that reduced sleep quantity can impair glucose metabolism and appetite regulation resulting in increased risk of obesity and diabetes. This current study provides the first evidence linking poor sleep quality to increased diabetes risk.
"These findings demonstrate a clear role for slow-wave sleep in maintaining normal glucose control," said the study's lead author, Esra Tasali, MD, assistant professor of medicine at the University of Chicago Medical Center. "A profound decrease in slow-wave sleep had an immediate and significant adverse effect on insulin sensitivity and glucose tolerance."
"Since reduced amounts of deep sleep are typical of aging and of common obesity-related sleep disorders, such as obstructive sleep apnea these results suggest that strategies to improve sleep quality, as well as quantity, may help to prevent or delay the onset of type 2 diabetes in populations at risk," said Eve Van Cauter, PhD, professor of medicine at the University of Chicago and senior author of the study.
The researchers studied nine lean, healthy volunteers, five men and four women between the ages of 20 and 31. The subjects spent two consecutive nights in the sleep laboratory, where they went to bed at 11 P.M., slept undisturbed but carefully monitored, and got out of bed 8.5 hours later, at 7:30 A.M.
The same subjects were also studied for three consecutive nights during which they followed identical nighttime routines. During this session, however, when their brain waves indicated that they were drifting into slow-wave sleep they were subtly disturbed by sounds administered through speakers beside the bed.
These sounds were loud enough to disrupt deep sleep but not so loud as to cause a full awakening. This technique enabled the researchers to decrease slow-wave sleep by about 90 percent, shifting the subjects from the onset of deep sleep (stage 3 or 4) to a lighter sleep (stage 2) without altering total sleep time.
"Our system proved quite effective," Tasali said. When asked about the sounds the next morning, study subjects vaguely recalled hearing a noise "three or four times," during the night. Some recalled as many as 10 to 15. On average, however, subjects required about 250-300 interventions each night, fewer the first night but more on subsequent nights as "slow-wave pressure," the body's need for deep sleep, accumulated night after night.
"This decrease in slow-wave sleep resembles the changes in sleep patterns caused by 40 years of aging," Tasali said. Young adults spend 80 to 100 minutes per night in slow-wave sleep, while people over age 60 generally have less than 20 minutes. "In this experiment," she said, "we gave people in their 20s the sleep of those in their 60s."
At the end of each study, the researchers gave intravenous glucose (a sugar solution) to each subject, then took blood samples every few minutes to measure the levels of glucose and insulin, the hormone that controls glucose uptake.
They found that when slow-wave sleep was suppressed for only three nights, young healthy subjects became about 25 percent less sensitive to insulin. As insulin sensitivity decreased, subjects needed more insulin to dispose of the same amount of glucose. But for eight of the nine subjects, insulin secretion did not go up to compensate for reduced effects. The result was a 23 percent increase in blood-glucose levels, comparable to older adults with impaired glucose tolerance.
Those with low baseline levels of slow-wave sleep had the lowest levels after having their sleep patterns disrupted and the greatest decrease in insulin sensitivity.
The alarming rise in the prevalence of type 2 diabetes is generally attributed to the epidemic of obesity combined with the aging of the population. "Previous studies from our lab have demonstrated many connections between chronic, partial, sleep deprivation, changes in appetite, metabolic abnormalities, obesity, and diabetes risk," said Van Cauter. "These results solidify those links and add a new wrinkle, the role of poor sleep quality, which is also associated with aging."
"Chronic shallow non-REM sleep, decreased insulin sensitivity and elevated diabetes risk are typical of aging," the authors conclude. "Our findings raise the question of whether age-related changes in sleep quality contribute to the development of these metabolic alterations."
This research was reported in the "Early Edition" of the Proceedings of the National Academy of Science, available online Dec. 31, 2007.
The National Institutes of Health funded this research. Additional authors include Rachel Leproult and David Ehrmann of the University of Chicago Medical Center.
Adapted from materials provided by University of Chicago Medical Center.
Why Wounds Are Slow To Heal In Diabetics
ScienceDaily (May 6, 2007 ) — Individuals with diabetes often experience slow or limited wound healing. Endothelial progenitor cells (EPCs), which derive from bone marrow, normally travel to sites of injury and are essential for the formation of blood vessels and wound healing.
In a study reported in the May 1st issue of the Journal of Clinical Investigation, Omaida Velazquez and colleagues from University of Pennsylvania Medical Center reveal why the numbers of these vital EPCs are decreased in the circulation and at wound sites in diabetes.
The authors examined diabetic mice and found that increased oxygen levels (hyperoxia) enhanced the mobilization of EPCs from the bone marrow to the peripheral blood circulation. The high oxygen levels increased the activation of the bone marrow enzyme eNOS, which stimulated nitric oxide production, helping to produce greater numbers of EPCs.
However, local injection of the chemokine stromal cell--derived factor 1 alpha (SDF-1alpha) was required to recruit these EPCs from the circulation to the wound site. The increased presence of EPCs at the wound site resulted in accelerated wound healing. The authors concluded that impaired eNOS activation and decreased SDF-1alpha expression in diabetes are responsible for the defect in diabetic wound healing.
In an accompanying commentary, Harold Brem and Marjana Tomic-Canic from Columbia University and Cornell University, respectively, reinforce that future therapeutics for diabetic wound healing will have to correct multiple deficiencies simultaneously. Therapeutic interventions, including correcting EPC activation via hyperbaric oxygen therapy and correcting EPC homing via administration of SDF-1alpha, may significantly accelerate diabetic wound healing by correcting the deficit in EPC number that is inherent to diabetic wounds.
Article: Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1alpha
Adapted from materials provided by Journal of Clinical Investigation.
Wednesday, December 12, 2007
Why Wounds Are Slow To Heal In Diabetics
ScienceDaily (
In a study reported in the May 1st issue of the Journal of Clinical Investigation, Omaida Velazquez and colleagues from University of Pennsylvania Medical Center reveal why the numbers of these vital EPCs are decreased in the circulation and at wound sites in diabetes.
The authors examined diabetic mice and found that increased oxygen levels (hyperoxia) enhanced the mobilization of EPCs from the bone marrow to the peripheral blood circulation. The high oxygen levels increased the activation of the bone marrow enzyme eNOS, which stimulated nitric oxide production, helping to produce greater numbers of EPCs.
However, local injection of the chemokine stromal cell--derived factor 1 alpha (SDF-1alpha) was required to recruit these EPCs from the circulation to the wound site. The increased presence of EPCs at the wound site resulted in accelerated wound healing. The authors concluded that impaired eNOS activation and decreased SDF-1alpha expression in diabetes are responsible for the defect in diabetic wound healing.
In an accompanying commentary, Harold Brem and Marjana Tomic-Canic from Columbia University and Cornell University, respectively, reinforce that future therapeutics for diabetic wound healing will have to correct multiple deficiencies simultaneously. Therapeutic interventions, including correcting EPC activation via hyperbaric oxygen therapy and correcting EPC homing via administration of SDF-1alpha, may significantly accelerate diabetic wound healing by correcting the deficit in EPC number that is inherent to diabetic wounds.
Article: Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1alpha
Adapted from materials provided by Journal of Clinical Investigation.
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