Tag Archives: Insulin resistance

An Increase in Leptin Could Promote Colorectal Cancer

While researchers have known that obesity increases the risk for the development of colon cancer, the underlying molecular mechanisms have remained unclear.
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Now, for the first time, researchers have found that an increase in leptin, a cytokine that is normally increased in obese or overweight individuals, may promote colorectal neoplasms by activating colorectal cancer stem cells.

Cancer stem cells constitute a small subfraction of tumor cells that are characterized by long lifespan and capacity for self-renewal, and are responsible for tumor development, resistance to treatments and cancer recurrence. In colon cancer, leptin is able to increase the growth, survival, and resistance to certain chemotherapy treatments in this key cell population.

Leptin, a fat tissue-derived pluripotent cytokine regulating appetite and energy balance in the brain, also controls many physiological and pathological processes in peripheral organs, including carcinogenesis.

Colon cancer has increased in developed countries, possibly due to sedentary lifestyles and high caloric diets. Prior research has linked obesity to colorectal cancer risk by .4-1.0 fold in men and up to 2.0 fold in premenopausal women.

“Since targeting cancer stem cells may be a translationally relevant strategy to improve clinical outcomes, interfering with leptin signaling by targeting leptin receptors might become a novel attractive option for colorectal cancer treatment, particularly in obese patients,” says senior author of the study, Eva Surmacz.

“It is important to consider that cancer stem cells have been identified in several human malignancies,” says Monica Bartucci, study co-author. “Understanding how cancer stem cells interact with a tumor environment, including hormones like leptin, is likely to have significant implications for treatment management of different cancer types in human patients. We hope, in collaboration with Dr. Surmacz, not only to test the effects of leptin antagonist compounds on colon cancer stem cells but also to study the results of leptin stimulation on cancer stem cells isolated in other cancer tissues.”

Source: Elements4Health

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Sweet Danger

“I cannot have diabetes,” exclaimed the middle-aged gentleman. “The laboratory results are wrong. My parents did not have diabetes, I am a vegetarian, and I do not even eat sweets.”

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Well, this man is living in a soap bubble that is about to burst. None of the reasons cited protects from the onset of diabetes. As far as family history is concerned, awareness and routine laboratory tests for metabolic diseases are a relatively new phenomenon. His parents may have had diabetes and may have died quietly of an undiagnosed complication like a heart attack.

India has 30 million known diabetics, the largest number in the world. The figure is mounting daily and is slated to escalate by 200 per cent. Most of the affected will be in the economically productive age group of 30-60. We have to find out ways to combat this epidemic, halt it and prevent our children from falling prey to it.
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Studies have shown that the possibility of developing diabetes depends on one’s genes, which are inherited from both parents, and the nurturing environment provided first in the womb and later by the mother.

To begin with, women should have the correct BMI (body mass index — weight divided by height in metre squared) of 23 before they become pregnant. Some women are undernourished and eat poorly. Their calorie intake is only 70 per cent of the required amount (2,000-2,200 calories for an active adult female). The protein content may be less than the recommended 075-1gm/kg. Both these situations result in poor foetal growth and an SFD (small for dates) baby.

Compensatory mechanisms come into play in SFD babies and they develop relative insulin resistance so as to maintain normal blood glucose concentrations. Vital organs like the brain and heart receive sufficient nutrition, but it is diverted away from the muscles.

These small babies exhibit a phenomenon called “catch up growth”. If fed adequately after birth, they attain normal weight for age and height within three years. In the process, they can develop impaired glucose tolerance as early as seven years of age.

Today’s teens have a different story. They are becoming obese on a diet of fast food and “time pass” television. Many girls are overweight when they get married. Pregnancy and well meaning advice to “rest and eat for two” do not help matters. Those who are obese (BMI more than 29) or diabetic during pregnancy can produce large babies (LFD or large for dates). These babies are exposed to excess nutrition in the womb. They secrete excess insulin, can develop insulin resistance and eventually diabetes. The problem is compounded if they are growing up in a family with faulty eating habits and little or no regular exercise.

Since we now know that the majority of us carries a gene which predisposes us to develop diabetes, it makes sense to thwart the march to disease.

Check your blood sugars once a year after the age of 25, even if you are asymptomatic, to be sure you don’t fall in the “prediabetic” category. Those who are prediabetic have a fasting blood sugar between 100 and 126mg/dl and a two-hour post prandial or oral glucose tolerance test value between 140 and 200mg/dl. Abnormal values may occur 15 years before the onset of overt diabetes. Without active intervention eventually 35 per cent go on to develop the disease. With effort and a change in lifestyle, 45 per cent can revert to normal.

Medical complications — which cause heart disease, stroke, peripheral vascular diseases, and eye and kidney problems – begin to set in during the prediabetic stage. Early identification and treatment can reduce the damage.

The BMI should be maintained at 23. This can be done by keeping the caloric intake between 1,500-2,000 calories a day. The diet should be low in fat, and contain four to six helpings of fruit and vegetables. But dieting alone will not help, as weight loss through starvation cannot be sustained. Food restriction should be combined with physical activity for 60 minutes every day. A brisk walk (five kilometres), or one hour of swimming or cycling will do the trick.

Blood pressure should be maintained at 130/80 or less. Salt restriction and weight loss alone may be sufficient to achieve this. If not, medication may be needed.

Lipid levels also need to be monitored in prediabetes as dyslpidaemia and altered glucose tolerance go hand in hand. Elevated lipid levels predispose to a stroke and heart attack. LDL should be below 100 mg/dl, HDL above 40mg/dl (above 50 mg/dl for women), and triglycerides below 150mg/dl. Reducing the total oil intake to 500 ml a month, checking labels for hidden fats in processed foods, and eating more soluble fibre (beans and oats) will help. If levels remain high the statin group of medications can be started.

If parents adopt a healthy lifestyle, children will soon follow suit. Perhaps this way we can reduce the impact of this devastating disease in the next generation.

Source
:The Telegraph (Kolkata, India)

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Advantage Aggression

Evolutionary shifts from hunting to farming and beyond brought about bodily changes that may have led to diseases such as diabetes.

The brain versus brawn debate has taken a curious turn. The collective decision taken by mankind over thousands of years to switch from a muscle-flexing “soldier’s” lifestyle to that of a brain-dominated “diplomat” is an underlying cause of the ticking diabetes time bomb, says a new theory proposed by a team of Indian researchers.

The hypothesis by Milind Watve — professor of biology at the Indian Institute of Science Education and Research (Iiser), Pune — and his colleagues argues that the loss of physical aggression, which our forefathers used abundantly to fend for food and mating opportunities, has resulted in a host of irreversible hormonal and metabolic changes. These evolutionary cues seem to have led to metabolic syndrome, a precursor to diabetes and many other life-threatening diseases, the researchers argue in a paper published in the journal Medical Hypothesis earlier this month.

More than 200 million people worldwide suffer from diabetes and the number is feared to shoot up to 366 million by 2030, according to a study in a journal of the American Diabetes Association. One in four of them will be from India. Some other major diseases associated with metabolic syndrome are hypertension, coronary artery disease and atherosclerosis.

In prehistoric societies, aggression was important for easier access to food and better mating opportunities. However, aggression has an energy cost, in terms of increased risk of getting injured. Therefore, when there is no need for aggression, or aggression is unlikely to be effective, it has to be controlled. A satiated individual does not need to be aggressive and therefore cues of food satiety — such as having a stomach full or energy reserve in the form of fat — should signal aggression control. Sexual satiety is also expected to arrest aggression. There is evidence to show that the underlying hormonal mechanisms for both are similar, say the scientists.

“We are talking about the normal and natural forms of physical aggression that were a routine part of our hunter-gatherer life. We are not referring to pathological aggression (which is caused by hypertension or behavioural disorders),” says Watve.

According to the Iiser scientist, such changes started to become prominent when humans began farming, about 10,000 years ago.

“Agricultural people naturally show more restraint than do hunter-gatherers, as their neighbours are fixed. But they still need to control their oxen with a whip, drive wolves or mad dogs, shoo away birds and rats, catch chicken, and so on. These are moderately aggressive activities and very useful, in terms of maintaining the hormonal balance,” Watve says. “But in urban life, we have given up even this form of physical aggression.”

The new theory is set to replace or encompass the “thrifty” gene hypothesis proposed by American population geneticist James Neel more than 40 years ago. According to this, insulin resistance — the way diabetes manifests in a human body — may have evolved as an adaptive trait that later turned pathological due to the changed lifestyle and diet. He hypothesised a “thrifty” genotype that helped survival in primitive life, which was characterised by intermittent periods of “feast and famine”.

One of the major shortcomings of this theory is that it deals only with energy metabolism, says Watve. “It offers no explanation as to why the immune system changes and why sexual functions alter,” he explains.

In defence of their hypothesis, the Pune researchers have listed 32 biochemical changes that are associated with both insulin resistance and loss of physical aggression. One of them is serotonin, a brain chemical. Studies in the past have shown that aggressive individuals have a low serotonin level as compared to submissive people. Similarly, a high level of serotonin is implicated in reducing sexual motivation. In a complex way, increased serotonin levels also lead to obesity and insulin resistance.

The study throws up another interesting aspect — the biological changes linked to reduced injury-proneness associated with a “diplomat” lifestyle. Aggressive behaviour facilitates the secretion of epidermal growth factor (EGF) — a protein that plays a role in healing wounds — in the saliva and other body fluids. This is in anticipation of wounds during fights. “EGF is also important in pancreatic beta cell regeneration. So chronic lack of injuries will ultimately lead to insulin deficiency as well,” Watve says.

To support their hypothesis, they also gathered evidence of similar changes in many hormones and biomolecules such as dopamine, melatonin, cholesterol, the sex hormones, ghrelin and endorphin.

Watve, however, says the study is more of a synthesis. “Everything in support already exists in literature,” he says. A huge volume of work had accumulated in the last 15 years. There were many unexplained aspects. “Someone had to join the pieces of the big puzzle. Only evolutionary biologists could have done it — and it happened to be us,” says Watve.

But not everybody is convinced. Anoop Misra, an internal medicine specialist at Fortis Hospital in New Delhi, thinks that though an interesting hypothesis, it has several contradictory facets. “The metabolic syndrome is multi-factorial and so is diabetes. Even if eventually proven, it may explain only 5-10 per cent cases of diabetes,” he says.

To Watve, the response is not unexpected. In the last three years, wherever he presented the work, it elicited three types of reactions. One is of curiosity and interest. Some are excited by the novelty of the concept and despite some scepticism, agree that it is worth serious thought. Some others simply ignore it as something from India not worth looking at. The third type of response is from people who have a very religious approach to science. They will oppose anything against their belief system as unscientific, although they may not have any sound argument against it.

The Pune team — which included researchers from the University of Pune and KEM Hospital and Research Centre — also designed an exercise regime based on their findings. “We tested it on a small number of patients. It actually worked,” smiles Watve.

Source: The Telegaph (Kolkata, India)

 

Drop that Pill

Multi-vitamin medicines may take you closer to diabetes:-

For decades, health-conscious people have been popping multi-vitamin tablets to stay healthy and prevent their body from “rusting”. But it may not be such a good idea, scientists now say, as the pills may actually make you prone to diabetes. In a major blow to the multi-billion dollar vitamin industry, researchers in Australia have gathered enough scientific evidence to show that synthetic antioxidants contained in multi-vitamin pills stunt the body’s ability to release insulin, an important hormone required to maintain healthy blood glucose levels.

Antioxidants, which are primarily multi-vitamin supplements, help the body maintain good health and vitality by mopping up what scientists call “reactive oxygen species” or ROS, a natural by-product of metabolism. Extremely reactive, the latter are capable of damaging cell structures and DNA, if not continuously removed from the system. Normally, a healthy body is capable of scavenging these harmful compounds on its own. But when one is chronically ill, this ability is severely compromised, thus creating a need for an external supply of antioxidants.

“Whether antioxidants really help depends on the user’s state of health,” says Tony Tiganis, associate professor of biochemistry and molecular biology at the Cellular Signalling and Human Disease Laboratory, Monash University, Australia, and leader of the study team.

The study, which appeared in the latest issue of the journal Cell Metabolism, suggests that mopping up the entire quantity of ROS from the body is not a good idea. That is because a low level of ROS can promote insulin response and attenuate insulin resistance in the early stages of type 2 diabetes. Insulin response can be best described as the body’s ability to release insulin — which removes sugar (or glucose) from blood, storing it away in muscles and fat cells.

“This is the first ever study to show that ROS can promote insulin sensitivity in vivo to prevent the development of insulin resistance,” Tiganis told KnowHow.

Experimenting with laboratory mice, Tiganis and his colleagues showed that the animals which lacked the ability to eliminate normal levels of ROS do not become insulin resistant even when put on a high-fat diet as they otherwise would have. These health benefits could be attributed to the increased release of insulin and uptake of ROS in their muscles, say the researchers.

“It is a pathbreaking study, the conclusions of which go against the prevailing scientific opinion that increase in oxidation (release of ROS) inhibits insulin action and predisposes one to diabetes,”
says Anoop Misra, internal medicine specialist at Fortis Hospital, New Delhi.

However, one must be careful in embracing the findings, cautions Misra. “The authors themselves say that only a subtle increase (and not gross) in oxidation can enhance sensitivity to insulin and that too in the early phase of the onset of diabetes.”

In practical terms, the general use of antioxidants (which are available in India in a wide variety, as vitamins and “strength giving” and “anti-ageing” pills) is best avoided, he observes.

It is not for the first time that the growing multi-vitamin industry is getting a bad press. Early last year, a study by Danish researchers — which appeared in the Journal of American Medical Association — showed that certain antioxidants could cut short the lifespan of an individual.

The study, which was an analysis of 67 random studies covering 2,00,000 people on antioxidant supplements, showed that some supplements — including vitamin A, beta-carotene and vitamin E — were capable of increasing mortality. Yet another suggested that an overdose of antioxidants could make men vulnerable to prostrate cancer.

In May this year, a team of researchers from Germany and the US showed that vitamin supplements could negate the health-promoting benefits of physical exercise. Published in the Proceedings of National Academy of Sciences, the study said supplements might lower the activity of several genes that are responsible for the body’s natural ROS scavenging mechanism.

Tiganis and other scientists, however, argue that they are not totally against intake of antioxidants. The body requires them and there are several natural sources of antioxidants such as fruits and vegetables. “There is a delicate balance; too much of a good thing… might be bad,” he says.

“I think healthy individuals should not take antioxidant supplements, but exercise and follow a healthy diet. It is possible that antioxidants may improve insulin sensitivity in obese diabetics,” he observes.

As a next step, the scientists are planning to work out at what stage ROS change from being beneficial to harmful.

So think again before you pop those pills in the morning.

Source: The Telegraph (Kolkata, India)

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Coconut Oil Could Ward Off Type 2 Diabetes.

Diet Rich  Coconut Oil Could Stop Type 2 Diabetes.  A diet rich in coconut oil could ward off Type 2 diabetes.

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The oil, used in foods such as margarine, helps prevent insulin resistance.

This is where muscle and fat cells stop reacting to insulin, the hormone that helps to mop up excess sugar in the blood.
Australian scientists used mice to compare the effects of coconut oil-rich foods with a lard-based diet, consumed by many in the developed world.
The results showed coconut-fed mice were much less likely to develop resistance to insulin. Previously, coconut oil has had a mixed reception because it is high in saturated fat, which is linked to high cholesterol.

But coconut fat is now known to be made up of so-called ‘medium chain’ fatty acids, regarded as healthier than the long-chain fatty acids found in animal products such as butter or lard.

Source: Mail online:23rd. Sept. 2009

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