Thursday, March 18, 2004
Scientists: Brain enzyme regulates appetite, weight
Scientists say an enzyme in the brain that monitors energy in cells also appears to regulate appetite and weight, a discovery that could lead to new treatments for obesity.
The enzyme is known as AMP-activated protein kinase, or AMPK. Its activity is regulated by the hormone leptin, which previously was linked to appetite suppression.
Harvard researchers found in experiments with mice that when AMPK was inhibited, the animals ate less and lost weight. When AMPK levels were boosted, the mice ate more and gained weight.
Barbara B. Kahn, the lead author of the study, said the work identifies a new leptin signaling pathway and a promising new target in humans.
"It will affect drug development and approaches for new preventions and treatments," Kahn said.
The study appears Wednesday in an online version of the journal Nature.
Dr. David Cummings, a University of Washington obesity researcher who was not involved in the work, said the findings complement recent work in Britain in which the hormone ghrelin, an appetite-stimulating hormone, also was found to affect AMPK levels.
Almost a third of American adults are obese, up from 14 percent a generation ago, according to government data. Only a few prescription weight-control drugs are on the market, and they produce only modest weight loss, either by suppressing appetite or by preventing the body from digesting and absorbing fats.
Cummings said studies show that hormone replacement therapy won't be a simple cure for the nation's obesity woes. Studies on using leptin to control weight found that obese people had lost sensitivity to the hormone, Cummings said.
Some researchers believe AMP-kinase might be more effective in weight control than leptin because its works more directly on appetite signaling at the end of the biochemical pathway in the brain. Clinical trials on human patients will take years to complete, researchers said.
Scientists say an enzyme in the brain that monitors energy in cells also appears to regulate appetite and weight, a discovery that could lead to new treatments for obesity.
The enzyme is known as AMP-activated protein kinase, or AMPK. Its activity is regulated by the hormone leptin, which previously was linked to appetite suppression.
Harvard researchers found in experiments with mice that when AMPK was inhibited, the animals ate less and lost weight. When AMPK levels were boosted, the mice ate more and gained weight.
Barbara B. Kahn, the lead author of the study, said the work identifies a new leptin signaling pathway and a promising new target in humans.
"It will affect drug development and approaches for new preventions and treatments," Kahn said.
The study appears Wednesday in an online version of the journal Nature.
Dr. David Cummings, a University of Washington obesity researcher who was not involved in the work, said the findings complement recent work in Britain in which the hormone ghrelin, an appetite-stimulating hormone, also was found to affect AMPK levels.
Almost a third of American adults are obese, up from 14 percent a generation ago, according to government data. Only a few prescription weight-control drugs are on the market, and they produce only modest weight loss, either by suppressing appetite or by preventing the body from digesting and absorbing fats.
Cummings said studies show that hormone replacement therapy won't be a simple cure for the nation's obesity woes. Studies on using leptin to control weight found that obese people had lost sensitivity to the hormone, Cummings said.
Some researchers believe AMP-kinase might be more effective in weight control than leptin because its works more directly on appetite signaling at the end of the biochemical pathway in the brain. Clinical trials on human patients will take years to complete, researchers said.
Thursday, March 11, 2004
Research: Breast cancer drug switch cuts recurrence
A drug for advanced breast cancer prevents localized tumors from returning after surgery better than the current mainstay drug, according to a large, international study that promises new hope and treatment strategies for many patients.
Recurrence of such early cancer was reduced by one-third in women who started on the gold standard treatment, tamoxifen, then switched after 21/2 years to the newer drug, exemestane, compared to those who took tamoxifen the whole time.
The women switching to exemestane, a hormonal drug sold under the brand Aromasin, also had less serious side effects, were 56 percent less likely to get cancer in the other breast and were half as likely to develop unrelated cancer in other body areas.
Dr. Jeff Abrams, the National Cancer Institute's associate chief of clinical research, said a recent study on exemestane "cousin" letrozole showed important advantages over tamoxifen for their class of drugs, called aromatase inhibitors. Abrams was not involved in the new study.
Lead researcher Dr. R.C. Coombes, professor of cancer medicine at Imperial College School of Medicine in London, predicted doctors will give exemestane to many women at high risk for recurrence, such as those whose breast cancer spreads to multiple lymph nodes.
"More work needs to be done to understand what's going on" at the molecular level, he said.
The study, which included 4,742 postmenopausal women in 37 countries, focused on women with breast cancer in which the hormone estrogen fuels tumor growth -- the type causing about 70 percent of breast cancer. The results do not apply to premenopausal women or those with tough-to-treat breast cancer not driven by estrogen.
Class of drugs examined
Normally, early-stage breast cancer is treated by surgery to remove the tumor, plus radiation, if part of the breast is conserved. If tumor cells had spread to underarm lymph nodes, cell-killing cancer drugs often are given, particularly in the United States.
Then, if the cancer is undetectable and it's the type fueled by estrogen, women take daily tamoxifen pills for five years -- to prevent any microscopic cancer cells lurking in the body from later triggering cancer in another spot. Such metastasized cancer is virtually incurable.
But cancer cells grow resistant to tamoxifen in many patients, sometimes within 12 months, and prolonged use can cause uterine cancer and dangerous blood clots.
Those problems sparked interest in hormonal drugs such as aromatase inhibitors, which dramatically suppress estrogen production by adrenal glands and other tissues by blocking the effects of the enzyme aromatase. Tamoxifen binds to specific tumor cell sites to keep estrogen from attaching and directing the cells to multiply.
Aromatase inhibitors have been around since the 1970s, but high toxicity limited use. Today's "third generation" aromatase inhibitors -- including Aromasin, Femara and Arimidex -- work better and are less toxic but still increase bone loss, a serious problem for elderly women, Coombes said.
His team reported interim results through last June from the study, which is nearly complete, in Thursday's edition of the New England Journal of Medicine.
The research was partly funded by Pfizer Inc., the maker of Aromasin.
Among the women switching to exemestane, 54 died of breast cancer, compared with 67 in the tamoxifen-only group. Overall, 91.5 percent of women in the exemestane group were cancer free three years after switching drugs, compared with 86.8 percent for women who stayed on tamoxifen.
"It confirms a trend that we've been seeing in treatment with metastatic disease," said Dr. Julia Smith, clinical associate professor of oncology at the NYU school of medicine and cancer institute. "This whole class of drugs looks very promising, very active."
A drug for advanced breast cancer prevents localized tumors from returning after surgery better than the current mainstay drug, according to a large, international study that promises new hope and treatment strategies for many patients.
Recurrence of such early cancer was reduced by one-third in women who started on the gold standard treatment, tamoxifen, then switched after 21/2 years to the newer drug, exemestane, compared to those who took tamoxifen the whole time.
The women switching to exemestane, a hormonal drug sold under the brand Aromasin, also had less serious side effects, were 56 percent less likely to get cancer in the other breast and were half as likely to develop unrelated cancer in other body areas.
Dr. Jeff Abrams, the National Cancer Institute's associate chief of clinical research, said a recent study on exemestane "cousin" letrozole showed important advantages over tamoxifen for their class of drugs, called aromatase inhibitors. Abrams was not involved in the new study.
Lead researcher Dr. R.C. Coombes, professor of cancer medicine at Imperial College School of Medicine in London, predicted doctors will give exemestane to many women at high risk for recurrence, such as those whose breast cancer spreads to multiple lymph nodes.
"More work needs to be done to understand what's going on" at the molecular level, he said.
The study, which included 4,742 postmenopausal women in 37 countries, focused on women with breast cancer in which the hormone estrogen fuels tumor growth -- the type causing about 70 percent of breast cancer. The results do not apply to premenopausal women or those with tough-to-treat breast cancer not driven by estrogen.
Class of drugs examined
Normally, early-stage breast cancer is treated by surgery to remove the tumor, plus radiation, if part of the breast is conserved. If tumor cells had spread to underarm lymph nodes, cell-killing cancer drugs often are given, particularly in the United States.
Then, if the cancer is undetectable and it's the type fueled by estrogen, women take daily tamoxifen pills for five years -- to prevent any microscopic cancer cells lurking in the body from later triggering cancer in another spot. Such metastasized cancer is virtually incurable.
But cancer cells grow resistant to tamoxifen in many patients, sometimes within 12 months, and prolonged use can cause uterine cancer and dangerous blood clots.
Those problems sparked interest in hormonal drugs such as aromatase inhibitors, which dramatically suppress estrogen production by adrenal glands and other tissues by blocking the effects of the enzyme aromatase. Tamoxifen binds to specific tumor cell sites to keep estrogen from attaching and directing the cells to multiply.
Aromatase inhibitors have been around since the 1970s, but high toxicity limited use. Today's "third generation" aromatase inhibitors -- including Aromasin, Femara and Arimidex -- work better and are less toxic but still increase bone loss, a serious problem for elderly women, Coombes said.
His team reported interim results through last June from the study, which is nearly complete, in Thursday's edition of the New England Journal of Medicine.
The research was partly funded by Pfizer Inc., the maker of Aromasin.
Among the women switching to exemestane, 54 died of breast cancer, compared with 67 in the tamoxifen-only group. Overall, 91.5 percent of women in the exemestane group were cancer free three years after switching drugs, compared with 86.8 percent for women who stayed on tamoxifen.
"It confirms a trend that we've been seeing in treatment with metastatic disease," said Dr. Julia Smith, clinical associate professor of oncology at the NYU school of medicine and cancer institute. "This whole class of drugs looks very promising, very active."
Tuesday, March 02, 2004
Asians choosing fat over fad as dietary habits undergo heavy change
SINGAPORE (AFP) - Asians are eating fewer carbohydrates but, unlike in the West where fad diets are leading people away from potatoes and pasta, a growing love of fatty foods is to blame, nutrition experts say.
Dieticians and nutrition researchers told AFP that Asians have yet to latch on to the increasingly popular Western diets such as the Atkins and South Beach formulas that preach low-carbohydrate and high-protein intakes.
But dietary habits in Asia are undergoing a perhaps even more profound change as consumption of rice and grain falls while eggs, edible oils, dairy products and other more fatty products become more popular.
"(Fad diets) exist in this part of the world but haven't really taken hold, although there is a lot of concern among Asians about putting on weight," Asian Food Information Centre (AFIC) executive director Georgina Cairns said.
"Twenty years ago, the Asian diet consisted of less than 15 percent of fat and in some countries even less than 10 percent, but now we're heading up to 30 percent."
Senior scientist at the Philippine-based International Rice Research Institute (IRRI) David Dawe attributed this dramatic shift in the Asian dietary pattern to rising incomes.
"Rice consumption will fall in every country in Asia as they get richer," he said.
"It's a universal law, every society is that way. As you become wealthier you eat less of your staple food and diversify your diet."
Figures collected by the IRRI showed that consumption of rice has almost halved in Japan, tumbled almost 30 percent in Malaysia and fallen about 20 percent in Thailand and South Korea over the past 40 years.
Globalization has also contributed to the rising popularity of fats in Asia, according to Cairns.
She said travel, international trade and cross-border expansions of Western food outlets had led to the growing intimacy between the Asian palate and rich Western fare.
"Even in Southeast Asia, with no tradition of eating cheese, more and more people like the taste of cheese," she said, adding this was contributing to taller Asian children, but also heavier ones.
"We're getting fat. The figures are worrying."
Although obesity is not as big a problem in Asia as it is in the United States, Britain and Australia, it is becoming increasingly common, AFIC said on its website.
Danny Oh, 38, a manager of a coffee chain outlet in Singapore, fits the stereotype of the fattening Asian and calls himself a "classic heart attack case".
Oh said his breakfast always consists of oily foods such as Indian pancakes known as roti prata and fried noodles. But he is not overly concerned about the health implications.
"I must have my cholesterol everyday," he said. "If I go, I go."
Equally nonchalant is 14-year-old Singaporean student Celestine Song, who eats at fast food outlets four times a week.
"I'm not very worried (for my health), because I exercise every week," she said.
Although fad diets, which have drawn criticism for promoting unbalanced eating, have not garnered a large following in Asia, Cairns said it did not mean Asians were free from other unhealthy misperceptions about weight loss.
"There is a tendency for people (in Asia) to see some food as having a miracle constituent in them -- something that will burn fat or block the calorie content of the food," Cairns said.
She cited grapefruits, green tea and herbal pills as popular items consumed by Asians seeking to shed weight.
"It's not good to see some food as miracles -- there aren't any miracle food."
Sales consultant Samantha Lu, 23, said she has not placed her faith in any specific food, but she is trying out a nutritional replacement diet programme, in which she drinks a special diet milkshake in place of certain meals.
Munching on a hamburger at a US fast food chain outlet in Singapore's business district, she looked down at herself and commented: "I haven't noticed any difference."
SINGAPORE (AFP) - Asians are eating fewer carbohydrates but, unlike in the West where fad diets are leading people away from potatoes and pasta, a growing love of fatty foods is to blame, nutrition experts say.
Dieticians and nutrition researchers told AFP that Asians have yet to latch on to the increasingly popular Western diets such as the Atkins and South Beach formulas that preach low-carbohydrate and high-protein intakes.
But dietary habits in Asia are undergoing a perhaps even more profound change as consumption of rice and grain falls while eggs, edible oils, dairy products and other more fatty products become more popular.
"(Fad diets) exist in this part of the world but haven't really taken hold, although there is a lot of concern among Asians about putting on weight," Asian Food Information Centre (AFIC) executive director Georgina Cairns said.
"Twenty years ago, the Asian diet consisted of less than 15 percent of fat and in some countries even less than 10 percent, but now we're heading up to 30 percent."
Senior scientist at the Philippine-based International Rice Research Institute (IRRI) David Dawe attributed this dramatic shift in the Asian dietary pattern to rising incomes.
"Rice consumption will fall in every country in Asia as they get richer," he said.
"It's a universal law, every society is that way. As you become wealthier you eat less of your staple food and diversify your diet."
Figures collected by the IRRI showed that consumption of rice has almost halved in Japan, tumbled almost 30 percent in Malaysia and fallen about 20 percent in Thailand and South Korea over the past 40 years.
Globalization has also contributed to the rising popularity of fats in Asia, according to Cairns.
She said travel, international trade and cross-border expansions of Western food outlets had led to the growing intimacy between the Asian palate and rich Western fare.
"Even in Southeast Asia, with no tradition of eating cheese, more and more people like the taste of cheese," she said, adding this was contributing to taller Asian children, but also heavier ones.
"We're getting fat. The figures are worrying."
Although obesity is not as big a problem in Asia as it is in the United States, Britain and Australia, it is becoming increasingly common, AFIC said on its website.
Danny Oh, 38, a manager of a coffee chain outlet in Singapore, fits the stereotype of the fattening Asian and calls himself a "classic heart attack case".
Oh said his breakfast always consists of oily foods such as Indian pancakes known as roti prata and fried noodles. But he is not overly concerned about the health implications.
"I must have my cholesterol everyday," he said. "If I go, I go."
Equally nonchalant is 14-year-old Singaporean student Celestine Song, who eats at fast food outlets four times a week.
"I'm not very worried (for my health), because I exercise every week," she said.
Although fad diets, which have drawn criticism for promoting unbalanced eating, have not garnered a large following in Asia, Cairns said it did not mean Asians were free from other unhealthy misperceptions about weight loss.
"There is a tendency for people (in Asia) to see some food as having a miracle constituent in them -- something that will burn fat or block the calorie content of the food," Cairns said.
She cited grapefruits, green tea and herbal pills as popular items consumed by Asians seeking to shed weight.
"It's not good to see some food as miracles -- there aren't any miracle food."
Sales consultant Samantha Lu, 23, said she has not placed her faith in any specific food, but she is trying out a nutritional replacement diet programme, in which she drinks a special diet milkshake in place of certain meals.
Munching on a hamburger at a US fast food chain outlet in Singapore's business district, she looked down at herself and commented: "I haven't noticed any difference."
Wednesday, February 25, 2004
Very-Low-Calorie Diet Controls Teens' Diabetes
A high-protein, low-carb, very-low-calorie diet is effective short-term treatment for obese adolescents with type 2 diabetes, according to a new study.
The rate of type 2 diabetes has risen exponentially among adolescents, Dr. Steven M. Willi and colleagues from the Medical University of South Carolina, Charleston, point out in the medical journal Diabetes Care, but there are few studies comparing the relative merits of diet, exercise, insulin, and other drug therapies in treating such patients.
The team evaluated the ability of a ketogenic, very-low-calorie diet to reduce weight, reduce high blood sugar levels, and decrease the dependence on anti-diabetes medications in 20 obese teens -- 5 males and 15 females -- with type 2 diabetes.
The diet consisted of about 100 grams of protein and less than 30 grams each of fat and carbohydrates per day, which delivered between 680 and 800 calories. That translates to approximately 13 ounces of lean meat and 3 cups of vegetables. The participants also needed to take in 8 cups of fluid and supplemental salt daily.
Mean daily blood glucose levels fell from 162 to 100 mg/dL within three days of beginning the diet, and all but one teen managed to discontinue all antidiabetic therapy.
After voluntarily stopping the diet after an average of 60 days, participants' average weight loss was 25 pounds (9.3 percent of total body weight), the researchers report.
In fact, the average body weight was still significantly reduced two years later. This amounted to a 5.4 percent reduction, compared with a 3.7 percent increase in an age-matched control group.
Average blood pressure also fell during the diet, and none of the patients experienced side effects such as nausea and cramps reported in previous trials of the diet in youngsters, Willi's team found.
The investigators call for further studies, but conclude that "the very-low-calorie diet has the potential to improve diabetes control over the short term and perhaps empower diabetic individuals over the long term."
A high-protein, low-carb, very-low-calorie diet is effective short-term treatment for obese adolescents with type 2 diabetes, according to a new study.
The rate of type 2 diabetes has risen exponentially among adolescents, Dr. Steven M. Willi and colleagues from the Medical University of South Carolina, Charleston, point out in the medical journal Diabetes Care, but there are few studies comparing the relative merits of diet, exercise, insulin, and other drug therapies in treating such patients.
The team evaluated the ability of a ketogenic, very-low-calorie diet to reduce weight, reduce high blood sugar levels, and decrease the dependence on anti-diabetes medications in 20 obese teens -- 5 males and 15 females -- with type 2 diabetes.
The diet consisted of about 100 grams of protein and less than 30 grams each of fat and carbohydrates per day, which delivered between 680 and 800 calories. That translates to approximately 13 ounces of lean meat and 3 cups of vegetables. The participants also needed to take in 8 cups of fluid and supplemental salt daily.
Mean daily blood glucose levels fell from 162 to 100 mg/dL within three days of beginning the diet, and all but one teen managed to discontinue all antidiabetic therapy.
After voluntarily stopping the diet after an average of 60 days, participants' average weight loss was 25 pounds (9.3 percent of total body weight), the researchers report.
In fact, the average body weight was still significantly reduced two years later. This amounted to a 5.4 percent reduction, compared with a 3.7 percent increase in an age-matched control group.
Average blood pressure also fell during the diet, and none of the patients experienced side effects such as nausea and cramps reported in previous trials of the diet in youngsters, Willi's team found.
The investigators call for further studies, but conclude that "the very-low-calorie diet has the potential to improve diabetes control over the short term and perhaps empower diabetic individuals over the long term."
