Diabetes increases risk of breast cancer and physical activity reduces the risk

Diabetes confers 27% increase in breast cancer risk

By: BRUCE JANCIN, Ob.Gyn. News Digital Network
SAN ANTONIO – Diabetes is independently associated with a 27% increased risk of breast cancer, but this elevated risk is confined to postmenopausal type 2 diabetic patients, a large meta-analysis has shown.

The meta-analysis, which included 40 published studies and 56,111 women with breast cancer, found no association between risk of the malignancy and circulating serum insulin level, insulin growth factor–1 level, fasting blood glucose level, or C-peptide concentration.

These findings suggest that the hyperinsulinemic theory of the pathogenesis of breast cancer may need to be reevaluated in order to account for the increased risk being confined to postmenopausal patients and unrelated to indices of metabolic control, Dr. Peter Boyle said at the annual San Antonio Breast Cancer Symposium.

The key risk factors for breast cancer that emerged from the meta-analysis were adiposity and lack of physical activity. Both are also well established as risk factors for diabetes.

Based on the findings from this meta-analysis, efforts to avoid overweight and increase physical activity should form the basis of a common public health strategy simultaneously aimed at preventing diabetes and breast cancer, according to Dr. Boyle of the International Prevention Research Institute in Lyon, France.

High levels of physical activity, whether occupational or recreational, were independently associated with a 17% reduction in the relative risk of being diagnosed with breast cancer in premenopausal women and a 12% decrease in the postmenopausal population.

The relationship between adiposity and breast cancer was less straightforward. Premenopausal women who were overweight or obese had a significantly lower breast cancer risk than did leaner women, while breast cancer risk was increased in adipose postmenopausal women. More specifically, a 5-U increase in body mass index – equivalent to an extra 14.5 kg in a woman 1.7 m tall – was associated with an 11% increased risk of breast cancer in postmenopausal women but a 10% reduction in risk in premenopausal women.

Dr. Boyle and coworkers also presented a related meta-analysis looking at breast cancer risk in women using insulin glargine (Lantus). The study was prompted by recent evidence linking pioglitazone to a possible increase in bladder cancer, liraglutide and pancreatic cancer, insulin use and lung cancer, and exenatide and pancreatic cancer.

This meta-analysis included 18 epidemiologic studies published within the past 3 years. Collectively the studies involved 4,080 cases of breast cancer in 903,675 patients followed for 2.7 million person-years.

The meta-analysis demonstrated no increase in breast cancer risk in insulin glargine users, compared with users of other insulins. Indeed, the risk of all forms of cancer was 9% lower in insulin glargine users, a statistically significant reduction. This was driven by a 14% reduction in the relative risk of colorectal cancer.

Another reassuring finding was that breast cancer risk did not increase with longer use of insulin glargine, as would be expected if a causal relationship existed, he added.

Both meta-analyses were funded by Sanofi-Aventis, which markets glargine. Dr. Boyle reported having no relevant financial conflicts, although several of his coinvestigators have served on advisory boards for Sanofi-Aventis and other insulin manufacturers.

Why Afternoon May Be the Best Time to Exercise

Original Article

Does exercise influence the body’s internal clock? Few of us may be conscious of it, but our bodies, and in turn our health, are ruled by rhythms. “The heart, the liver, the brain — all are controlled by an endogenous circadian rhythm,” says Christopher Colwell, a professor of psychiatry at the University of California, Los Angeles’s Brain Research Institute, who led a series of new experiments on how exercise affects the body’s internal clock. The studies were conducted in mice, but the findings suggest that exercise does affect our circadian rhythms, and the effect may be most beneficial if the exercise is undertaken midday.

For the study, which appears in the December Journal of Physiology, the researchers gathered several types of mice. Most of the animals were young and healthy. But some had been bred to have a malfunctioning internal clock, or pacemaker, which involves, among other body parts, a cluster of cells inside the brain “whose job it is to tell the time of day,” Dr. Colwell says.

These pacemaker cells receive signals from light sources or darkness that set off a cascade of molecular effects. Certain genes fire, expressing proteins, which are released into the body, where they migrate to the heart, neurons, liver and elsewhere, choreographing those organs to pulse in tune with the rest of the body. We sleep, wake and function physiologically according to the dictates of our body’s internal clock.

But, Dr. Colwell says, that clock can become discombobulated. It is easily confused, for instance, by viewing artificial light in the evening, he says, when the internal clock expects darkness. Aging also worsens the clock’s functioning, he says. “By middle age, most of us start to have trouble falling asleep and staying asleep,” he says. “Then we have trouble staying awake the next day.”

The consequences of clock disruptions extend beyond sleepiness. Recent research has linked out-of-sync circadian rhythm in people to an increased risk for diabetes, obesity, certain types of cancer, memory loss and mood disorders, including depression.

“We believe there are serious potential health consequences” to problems with circadian rhythm, Dr. Colwell says. Which is why he and his colleagues set out to determine whether exercise, which is so potent physiologically, might “fix” a broken clock, and if so, whether exercising in the morning or later in the day is more effective in terms of regulating circadian rhythm.

They began by letting healthy mice run, an activity the animals enjoy. Some of the mice ran whenever they wanted. Others were given access to running wheels only in the early portion of their waking time (mice are active at night) or in the later stages, the equivalent of the afternoon for us.

After several weeks of running, the exercising mice, no matter when they ran, were found to be producing more proteins in their internal-clock cells than the sedentary animals. But the difference was slight in these healthy animals, which all had normal circadian rhythms to start with.

So the scientists turned to mice unable to produce a critical internal clock protein. Signals from these animals’ internal clocks rarely reach the rest of the body.

But after several weeks of running, the animals’ internal clocks were sturdier. Messages now traveled to these animals’ hearts and livers far more frequently than in their sedentary counterparts.

The beneficial effect was especially pronounced in those animals that exercised in the afternoon (or mouse equivalent).

That finding, Dr. Colwell says, “was a pretty big surprise.” He and his colleagues had expected to see the greatest effects from morning exercise, a popular workout time for many athletes.

But the animals that ran later produced more clock proteins and pumped the protein more efficiently to the rest of the body than animals that ran early in their day.

What all of this means for people isn’t clear, Dr. Colwell says. “It is evident that exercise will help to regulate” our bodily clocks and circadian rhythms, he says, especially as we enter middle age.

But whether we should opt for an afternoon jog over one in the morning “is impossible to say yet,” he says.

Late-night exercise, meanwhile, is probably inadvisable, he continues. Unpublished results from his lab show that healthy mice running at the animal equivalent of 11 p.m. or so developed significant disruptions in their circadian rhythm. Among other effects, they slept poorly.

“What we know, right now,” he says, “is that exercise is a good idea” if you wish to sleep well and avoid the physical ailments associated with an aging or clumsy circadian rhythm. And it is possible, although not yet proven, that afternoon sessions may produce more robust results.

“But any exercise is likely to be better than none,” he concludes. “And if you like morning exercise, which I do, great. Keep it up.”

Fruits and Veggies!

Nutrients in Fruits, Vegetables May Help Prevent Breast Cancer: Study

THURSDAY Dec. 6, 2012 -- Women with higher levels of micronutrients found in many fruits and vegetables may be less likely to develop breast cancer, a new study finds.

Previous research has shown that the nutrients, called carotenoids, can inhibit tumor growth and reduce the spread of breast cancers.

"Carotenoids are found in carrots, spinach, kale, tomatoes, bell peppers, sweet potatoes and other vegetables," noted one expert not connected to the study, Dr. Stephanie Bernik.

"There has been some evidence in the past that these substances are helpful in reducing the risk of cancer," said Bernik, who is chief of surgical oncology at Lenox Hill Hospital in New York City.

In the new study, researchers led by A. Heather Eliassen of Brigham and Women's Hospital and Harvard Medical School, in Boston, analyzed data from thousands of women who took part in eight previous studies on carotenoid levels and breast cancer.

They found a statistically significant association between higher levels of carotenoids and reduced breast cancer risk, especially so-called ER-negative breast cancers -- tumors that aren't reliant on estrogen to fuel their growth. The findings highlight carotenoid levels as one of the first modifiable risk factors to be identified for ER-negative breast cancers, the team said.

While there is some evidence that carotenoids also inhibit the growth of ER-positive breast cancers (cancers that respond to estrogen), it's possible that this benefit is hidden by hormone-related associations that overpower other risk factors, the researchers added.

"A diet high in carotenoid-rich fruits and vegetables offers many health benefits, including a possible reduced risk of breast cancer," they concluded.

Bernik agreed. She said the researchers "have shown that there appears to be a real benefit to higher circulating levels of the micronutrients. The present study has more conclusively shown that there probably is some truth to what we tell patients regarding their diets ... the foods that your mother always told you are good for you, truly are good for you."

The study was published Dec. 6 in the Journal of the National Cancer Institute.

The study found a link between carotenoid levels and breast cancer risk, but it did not prove that the nutrients prevent the disease.

More information