How Fatty Foods Lead to Diabetes

Findings provide further evidence of importance of choosing foods low in unhealthy saturated fats

FINALLY, new research from the University of North Carolina at Chapel Hill School of Medicine adds clarity to the connection between high saturated fat diet and type 2 diabetes.

Several decades ago scientists noticed that people with type 2 diabetes have overly active immune responses, leaving their bodies rife with inflammatory chemicals. In addition, people who acquire the disease are typically obese and are resistant to insulin, the hormone that removes sugar from the blood and stores it as energy.

But for years no one has known exactly how the connection between high levels of body fat (obesity), inflammation and insulin resistance, three factors that are known to increase type 2 diabetes risk.

The Chapel Hill study has found that saturated fatty acids ‒ but not the unsaturated type ‒ can activate immune cells to produce an inflammatory protein, called interleukin-1beta. 

Using mouse cell lines (in vitro) and genetically engineered (defective inflammasome pathway) and wild-type mice (in vivo), the researchers found that intake of the saturated fatty acid palmitate, activates the NLRP3-ASC inflammasome-triggering production of IL-1beta, as well as the additional inflammatory factors caspase-1 and IL-18.

The activation of the inflammasome then impairs insulin signaling in several target tissues, such as muscle and adipose fat, thus reducing glucose tolerance and insulin sensitivity. IL-1beta also affects insulin sensitivity through tumor necrosis factor-α-independent and dependent pathways. When fed with a high-fat diet, mice with a defective inflammasome pathway had better maintenance of glucose homeostasis and higher insulin sensitivity.

The Chapel Hill researchers found that induction of the inflammasome by saturated palmitate is distinguished by its use of the AMP-activated protein kinase and unc-51-like kinase-1 autophagy-signaling pathways, and the presence of mitochondrialreactive oxygen species.

"The cellular path that mediates fatty acid metabolism is also the one that causes interleukin-1beta production. Interleukin-1beta then acts on tissues and organs such as the liver, muscle and fat (adipose) to turn off their response to insulin, making them insulin resistant. As a result, activation of this pathway by fatty acid can lead to insulin resistance and type 2 diabetes symptoms,” explains senior study co-author Jenny Y. Ting, PhD, William Kenan Rand Professor in the Department of Microbiology and Immunology

In layman terms, a diet rich in saturated fat, in addition to causing weight gain, activates certain cells of the immune system, instructing them to produce a protein called interleukin-1beta. This molecule is known to cause inflammation throughout the body.

This molecular complex inside cells, called the inflammasome, plays an important role in immunity by triggering inflammation in response to a wide variety of harmful agents ranging from bacteria to asbestos. This inflammation, in turn, affects the tissue of muscles, the liver and other organs, impairing their ability to react to insulin. This characteristic is one of the hallmarks of type 2 diabetes

Ting and colleagues have found that palmitate, a fatty acid common in a high fat diet, triggers activation of the inflammasome. Palmitate-triggered inflammation is also responsible for interfering with the insulin sensitivity of liver cells ― a major feature of type 2 diabetes.

In addition to explaining a poorly understood set of processes that were known to increase type 2 diabetes risk, the findings also provide further evidence of the importance of choosing foods low in unhealthy saturated fats. The researchers found that unsaturated fats, like omega-3s, did not activate this process.

Study To Check If Garlic And Asparagus Can Fight Diabetes

Researchers are investigating whether foods including garlic and asparagus could help weight loss and diabetes. In news that could make ardent vegans and vegetarians feel a little smug, the charity Diabetes UK is examining whether foods rich in fibre could supress people's appetites and reduce their blood sugar levels.

Fermentable carbohydrates, a kind of fibre, are found in foods such as asparagus, garlic, chicory and Jerusalem artichokes. If the foods are found to have this effect it could revolutionise treatments to tackle obesity and type 2 diabetes. Recent research has suggested that foods high in fermentable carbohydrates are particularly good at stabilising blood sugar levels.

The three-year study by the Nutrition and Research Group at Imperial College London, aims to establish whether these carbohydrates cause the release of gut hormones that could reduce appetite and enhance insulin sensitivity, which could reduce blood sugar levels and help control weight. The carbohydrates will be given to participants in the study as a daily supplement.

Dietitian Nicola Guess, who is leading the study, said: "By investigating how appetite and blood glucose levels are regulated in people at high risk of type 2 diabetes, it is hoped that we can find a way to prevent its onset. Type 2 diabetes accounts for 90% of diabetes cases and, if left untreated, can lead to serious health complications including heart disease, stroke, blindness, kidney failure and amputation, according to Diabetes UK.

Dr Iain Frame, the charity's director of research, said: "It is unlikely that any single measure used on its own will bring about improved prevention of type 2 diabetes. But it's hoped that the research being funded at Imperial College will help by aiming to develop an easy and affordable way to help people to reduce their risk of developing type 2 diabetes and managing their blood glucose levels."

Thank you David Batty/Guardian

Surgical Procedure Can Control Type 2 Diabetes, Claims Brazilian Surgeon

A new procedure which requires surgical intervention through Ileal Transposition (or small intestinal switch) can effectively control Type 2 diabetes, a Brazilian surgeon claimed in Hyderabad, India on August 21.

Dr Aureo Ludovico de Paula, was in the city to address the first international conference and live workshop on this procedure along with his Indian counterpart Dr Surendra Ugale.

Ugale who is also the organizing secretary of the workshop said, “the new research has shown that there are some intestinal hormones which have a great effect on the pancreas and insulin secretion especially in response to food intake. Dr Paula has devised a laparoscopic operation which he claims is proving to be a cure for Type 2 diabetes.”

Paula said, “The surgery can control diabetes without insulin, arrest the metabolic syndrome of the body organ deterioration, thus avoiding future diabetic complications.”

The doctor who has performed 700 surgeries with 95% remissions said the operation involves a long segment of ilium (ending portion of small intestine) which is shifted to the upper small intestinal area, where food particles will reach it very soon on eating a meal.

This causes an immediate secretion of good hormone GLP-1 which acts on the B cells of pancreas to secrete insulin and control blood sugar.

The fall out is a biochemical process that facilitates insulin secretion in the presence of undigested food and controls Type 2 diabetes, a metabolic disorder that is marked by the failure to absorb sugar and starch due to lack of the hormone insulin, Paula said.

Type 2 diabetes is the most common form of diabetes. In this disease, either the body does not produce enough insulin or the cells ignore it.

Ugale explained that Type 2 Diabetes affects several organs. The solution therefore is to stimulate these hormones in lower intestine that in turn secrete GLP which in turn stimulates the pancreas to stimulate the insulin and get fresh beta cells.

He said patients who already have diabetes for ten years and using medication, and are suffering from five associated diseases are ideal candidates for this kind of surgical intervention which costs less than US $10,000 (in India).

The surgery not only controls high blood pressure but also improves kidney cholesterol nerves reduces excess weight and also one need not take any medicines. He also can eat normally post surgery, including sweets.

However, doctors insist that first of all in any patient they would advise lifestyle changes, exercise followed by medication, if there is diabetes and if the patient is not doing well only then surgery is advised.

Presently a centre in Mumbai and Hyderabad are performing this surgery. A centre has also come up in Coimbatore.

Over hundred doctors from all over the country and endocrinologists are participating in the two-day seminar

Drugs Cannot Treat The Underlying Cause of Diabetes!

If you or someone you know is diabetic and taking medication for it, please understand that you cannot successfully treat the underlying cause of diabetes with drugs.

Avandia - the controversial drug that is linked to increased incidents of heart attacks (see my earlier posts) - works by making diabetes patients more sensitive to their own insulin, helping to control blood sugar levels.

In fact, most conventional treatments for type 2 diabetes utilize drugs that either raise insulin or lower blood sugar. Avandia, for example, lowers your blood sugar levels by increasing the sensitivity of liver, fat and muscle cells to insulin.

But you must understand that diabetes is NOT a blood sugar disease you may have been led to believe.

Type 2 diabetes is actually a disease caused by insulin resistance and faukty leptin signalling, both of which are regulated through your diet.

Conventional treatment, which is focused on fixing the symptom of elevated blood sugar rather than addressing the underlying disease, is doomed to fail in most cases.

Type 2 diabetes is virtually 100 percent avoidable, and can be effectively treated without medications in about the same percentage of cases.

Leptin, a relatively recently discovered hormone produced by fat, tells your body and brain how much energy it has, whether it needs more (saying "be hungry"), whether it should get rid of some (and stop being hungry) and importantly what to do with the energy it has (reproduce, upregulate cellular repair, or not).

In fact, the two most important organs that may determine whether you become (type 2, insulin resistant) diabetic or not are your liver and your brain, and it is their ability to listen to leptin that will determine this.

How is this done?

Well, that's the kicker. The only known way to reestablish proper leptin and insulin signaling is through a proper diet and exercise!

There is NO drug that can accomplish this, but following these simple guidelines can help you do at least three things that are essential for successfully treating diabetes: recover your insulin/leptin sensitivity, help normalize your weight, and naturally normalize your blood pressure.

As an aside, none of these will drastically raise your risk of a heart attack the way Avandia will … and in fact will have only positive benefits on your heart and your entire body:

• Severely limit or eliminate sugar and grains in your diet, especially fructose which is far more detrimental than any other type of sugar.Finding out your nutritional type will help you do this without much fuss. While nearly all type 2 diabetics need to swap out their grains for other foods, some people will benefit from using protein for the substitution, while others will benefit from using more vegetable-only carbohydrates. Therefore, along with reducing grains and sugars, determining your nutritional type will give you some insight into what foods you should use to replace the grains and sugars.
• Exercise regularly -- a must for anyone with diabetes or pre-diabetes. Typically, you'll need large amounts of exercise, until you get your blood sugar levels under control. You may need up to an hour or two a day. Naturally, you'll want to gradually work your way up to that amount, based on your current level of fitness.
• Avoid trans fats
• Get plenty of omega-3 fats from a high quality, animal based source.
• Get enough high-quality sleep every night.
• Optimize your Vitamin D levels. Recent studies have revealed that getting enough vitamin D can have a powerful effect on normalizing your blood pressure and that low vitamin D levels may increase your risk of heart disease.
• Monitor your fasting insulin level. This is every bit as important as your fasting blood sugar. You'll want your fasting insulin level to be between 2 to 4. The higher your level, the worse your insulin receptor sensitivity is.

So please remember that a drug will never treat the underlying cause of type 2 diabetes the way these lifestyle changes will.

It looks like Avandia is set to go the way of Vioxx, which was also pulled from the market after killing 60,000 people. You don't need to wait for the red tape to be removed to start looking out for your own health.

(Adapted from an article in Mercola.com) 

Scientists Uncover Novel Anti-Diabetes Mechanism

In a joint study, scientists from The Scripps Research Institute and the Dana-Farber Cancer Institute at Harvard University have uncovered a novel mechanism that dramatically increases insulin sensitivity and reduces the risk of developing type 2 diabetes and cardiovascular disease.

These findings offer a potent new target in the continuing search for new and improved anti-diabetic treatments. 

The new study, which focuses on controlling a fat-regulating protein known as PPARy, was published July 22, 2010, in the journal Nature (Volume 466, Issue 7304).

"The field has become interested in finding drugs that can promote increased insulin sensitization but not activate the classical fat cell generating pathway of PPARγ," said Patrick R. Griffin, chairman of the Department of Molecular Therapeutics at Scripps Florida who headed up the Scripps Research part of the study.

"We examined the mechanism of action of compounds that bind to PPARγ that improve insulin sensitivity but have minimal induction of fat. It was clear from the studies that these compounds have a unique but overlapping mechanism with the class of drugs used clinically that target PPARγ."

Adipose or fat tissue lies at the center of the metabolic syndrome, a cluster of risk factors that increases the possibility of type 2 diabetes, as well as stroke, coronary artery disease, even certain cancers. Of those risk factors, excessive body fat is considered the most problematic.

PPARγ can be considered the master gene of fat cell biology because it drives the conversion of cellular precursors into fat cells.

The collaborative studies showed obesity causes a modification on PPARγ that leads to alterations in the expression of a number of genes, including a reduction in the production of an insulin-sensitizing protein (adiponectin). This leads to an increase in insulin resistance.

The reprogramming of genes controlled by PPARγ occurs when it undergoes phosphorylation (a phosphate group is added to a protein) by the cdk5 kinase, an enzyme that is involved in a number of important sensory pathways and that can be activated by pro-inflammatory proteins.

The scientists were able to use both full and partial agonists (compounds that activate a cellular response) to reverse these phosphorylation effects and improve the production of adiponectin.

These results strongly suggest that cdk5-mediated phosphorylation is involved in the development of insulin-resistance and open the door to a novel opportunity for creating an improved generation of anti-diabetic drugs.

In 2007, Griffin and his colleagues published a study in the journal Structure (October 16, 2007, Volume 15, Number 10, pp.1258-1271) that explained the difference between how full and partial agonists interacted with PPARγ. Full agonists interacted strongly with a region of the receptor known to be important for the classical fat generation program.

On the other hand, partial agonists, which are poor agonists of the receptor, did not interact with this region at all but interacted more strongly with a potentially critical region of the receptor. From a drug development point of view, these results offered a new area of the protein to focus on to optimize therapeutic molecules that would be potent insulin sensitizers without driving fat generation.

"Bruce Spiegelman at Dana-Farber was starting to uncover the fact that the phosphorylation of PPARγ takes place in the very region where MRL-24, one of the partial agonists interacted," Griffin said. "I suggested that compounds like MRL24 might be better at antagonizing the cdk5 site given their strong interaction in this region of the receptor. For the new study, we provided significant amounts of compound to support the animal studies and provided an plausible mechanism for how partial agonists might recruit co-activator proteins to the cdk5 surface of PPARg."

While the team found that PPARγ phosphorylation effects were reversed by both full and partial agonists, partial agonists indeed accomplished this as well or better than the full agonists. Mimicking the effects of just blocking the phosphorylation event by mutation of the site on the receptor showed improvements in the production of adiponectin.

The new study also suggests a unified framework for understanding the relationship between fat cell dysfunction in obesity and anti-diabetic therapies based on PPARγ. In animal studies, high fat diets activate the cdk5 kinase, initiating phosphorylation, disrupting a number of key metabolic regulators including adiponectin and adipsin, a fat cell-selective gene whose expression is altered in obesity.

"The great paradox of this whole effort is we're targeting a receptor critical for fat production to offset the problem of fat overproduction," Griffin said. "Unfortunately, current drugs that target PPARg increase fat as one of their unwanted long-term side effects."

While the study is a big step forward, important questions still remain such as does a high fat diet and obesity lead to activation of cdk5 in non-fat tissues, Griffin said, since the negative effects of obesity extend far beyond metabolic syndrome to diseases like cancer and neurodegeneration.

More information: "Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARγ by Cdk5," Jang Hyun Choi, et al. Nature Volume 466, Issue 7304

Courtesy: The Scripps Research Institute

Coffee Ameliorates Effects Of Hyperglycemia, Say Researchers

Drinking coffee may help prevent diabetes, according to a new study published in the Journal of Agricultural and Food Chemistry (2010;58(9):5597-603).

Researchers fed either water or coffee to a group of laboratory mice commonly used to study diabetes. Coffee consumption prevented the development of high-blood sugar and also improved insulin sensitivity in the mice, thereby reducing the risk of diabetes.

Coffee also caused a cascade of other beneficial changes in the fatty liver and inflammatory adipocytokines related to a reduced diabetes risk. Additional lab studies showed that caffeine may be “one of the most effective anti-diabetic compounds in coffee,” the scientists said.

Researchers at Nagoya University have also reported evidence that drinking coffee may help prevent diabetes, and that coffee can ameliorate the effects of fatty liver, hyperglycemia and improve insulin sensitivity.

The research, published in the Journal of Agricultural and Food Chemistry, fed diabetes-prone mice either water or diluted coffee for five weeks. The coffee-drinking mice showed improved insulin sensitivity, reduced fatty liver and lower levels of inflammatory adipocytokines - all factors known to reduce the risk of type 2 diabetes.

Previous research has also linked coffee drinking to lowered risk of diabetes. A meta-analysis of research, conducted last year at the George Institute for International Health at the University of Sydney, found that each cup of coffee was associated with a 7% reduction in the excess risk of diabetes, and those drinking 3-4 cups a day had a 25% lower risk between those drinking 0-2 cups.

Even decaffeinated coffee had an effect, with those drinking 3-4 cups of decaf a day clocking a 33% lower risk than non-drinkers. Tea had less of an effect, with 3-4 cups a day translating to one-fifth lower risk than those who drank none.

These protective effects appeared to be independent of other potentially confounding variables. The link between decaf coffee and lowered risk suggests that the active component is more than just caffeine, although the Nagoya research suggests it may be one of the most effective components.

Diabetes: Preventing Hypoglycemia

A team of Boston researchers has developed an artificial pancreas that prevented blood sugar from falling perilously low (hypoglycemia) in a trial

 

Boston researchers have made a major step toward the development of an artificial pancreas that overcomes the bugaboo of most previous such attempts -- dangerously low blood sugar caused by injection of too much insulin.

Their experimental device secretes two hormones normally produced by the pancreas -- insulin and its counterbalancing hormone, called glucagon -- and has been shown to control blood sugar levels in about a dozen people for at least 24 hours, they reported Wednesday.

The team is now planning longer trials as they gear up for what they hope will be approval by the Food and Drug Administration in as little as seven years.

"This is a very important proof-of-concept study," said Dr. Irl B. Hirsch, an endocrinologist at the University of Washington School of Medicine, who was not involved in the research. "It was becoming obvious that if we were ever going to get [an artificial pancreas], we would have to use both hormones. . . . The fact that they have been able to do so successfully is very big and very exciting news."

Most people know that Type 1 diabetes, which affects more than a million Americans, is caused by the loss of insulin-secreting beta cells in the pancreas.

Few realize, however, that the disease also affects alpha cells of the pancreas, which secrete glucagon to raise the level of sugar in the blood. Together, the two hormones help the body in the delicate balancing act of maintaining blood sugar levels that are neither too high nor too low.

Researchers have made tremendous advances in controlling blood sugar levels with continuous monitors and insulin pumps, "but one of the challenges is that we have an accelerator but not a brake," which means blood sugar levels can fall too much, said molecular biologist Aaron Kowalski, a vice president of the Juvenile Diabetes Research Foundation, which partially sponsored the new research. The glucagon research, reported in the journal Science Translational Medicine, may provide that brake.

The brake is crucial, Kowalski added, because low blood sugar, or hypoglycemia, can cause seizures and even be fatal. For people who have been on insulin for long periods, the risk of hypoglycemia appears to grow over time, but it is also a problem in young children. "That's what keeps us awake at night," said Hirsch, who has been diabetic for 46 years.

What the Boston team has invented is a computer algorithm that responds to changes in blood sugar and computes how much insulin or glucagon to inject. Biomedical engineer Edward Damiano of Boston University began developing it a decade ago when his then-11-month-old son, David, was diagnosed with diabetes. He put the algorithm in a laptop and paired it with off-the-shelf insulin pumps -- which could also be used to inject glucagon -- and glucose monitors that are implanted under the skin.

After Damiano proved the system would work in diabetic pigs -- which are remarkably similar to humans physiologically -- Dr. Steven Russell of Massachusetts General Hospital suggested that it be tested in humans. Their first trials were conducted with 11 diabetics, who were hospitalized for 27 hours for the tests.

It was "a really rigorous test," Russell said. "We fed them three very-high-carbohydrate meals, which is the most challenging part of automated control."

Six of the patients experienced no hypoglycemia, but five had episodes that required they drink orange juice to recover. Subsequent analysis showed that those patients absorbed and metabolized insulin more slowly than normal. When Damiano adjusted the algorithm to account for this slowed absorption, all passed a repeat of the trial with flying colors -- as did the six who did well the first time around.

The next test, perhaps beginning next month, will involve a larger group who will be on the devices for at least two days in the hospital. They will use a portable form of the system that will allow them to walk around and exercise on a treadmill, which is another challenge for automated systems.

A key problem is developing a stable solution of glucagon that can be used in the pump without decomposing, an effort that is being pursued by several companies.

But because that may produce delays in commercializing a pump that uses both hormones, Damiano and Russell think an insulin-only device will be first to market, in about five years. A device that uses both hormones might follow within a couple of years.

"I am committed to trying to get something along fast enough that it could develop into a commercial product before my kid goes to college," Damiano said.

thomas.maugh @latimes.com

Lack Of Sleep New Risk For Diabetes

A new small-scale study reveals sleeplessness has a negative effect on insulin in the body. Researchers examined insulin sensitivity in healthy people after 8 hours of sleep then again after 4 hours of sleep. Less sleep caused more insulin resistance.

(I can say there's some truth in this thesis. Any time I have a late night, my fasting sugar next morning is in the 140-50 range as opposed to 100-120 when I've had 7-8 hours of sleep.)

The goal of the study was to understand whether insulin sensitivity is a fixed entity in people with normal glucose levels. Sleeplessness however, exposed insulin sensitivity in people without diabetes. The study raised questions on whether Western society's sleeping habits are helping the rising diabetes rates.

Other entities are factors as well, lifestyle choices, obesity or juvenile diabetes, but if one or more factor is prevalent, the risks are higher for developing full-blown diabetes.

"Sleep duration has shortened considerably in western societies in the past decade and simultaneously, there has been an increase in the prevalence of insulin resistance and type 2 diabetes," stated Dr. Esther Donga, of the Leiden University Medical Center in the Netherlands in Health Day News.

"The co-occurring rises in shortened sleep and diabetes prevalence may not be a coincidence. Our findings show a short night of sleep has more profound effects on metabolic regulation than previously appreciated."

Lack of sleep produces other health concerns as well, but consecutive nights of very little sleep could be contributing to diabetes risks. Glucose tolerance is therefore affected by rest according to the study.

The study is schedule for release in June and will be published in the Journal of Clinical Endocrinology & Metabolism.

Thank you Amy Munday for the info