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Sleep Apnea Linked to Carb Craving in Diabetes

Sleep Apnea study at Palm Beach Research
June 15, 2012 (Boston, Massachusetts) — In a small study of patients visiting a sleep clinic in New Jersey, researchers found that those with type 2 diabetes were at high risk for sleep apnea and that sleep apnea was associated with carbohydrate craving. "Since the prevalence of sleep apnea among diabetics was high in this study, along with the fact that the risk of carbohydrate craving was also very elevated in this group, primary care physicians as well as endocrinologists need to routinely screen for sleep apnea among type 2 diabetics," Mahmood I. Siddique, DO, from Sleep & Wellness Medical Associates LLC, Hamilton, New Jersey, told Medscape Medical News. He presented the study findings this week at SLEEP 2012: Associated Professional Sleep Societies 26th Annual Meeting. Changes in Leptin and Ghrelin "Studies among the general population have shown that sleep apnea and sleep deprivation may affect carbohydrate craving by hormonal changes in leptin and ghrelin," said Dr. Siddique, associate clinical professor of medicine, Robert Wood Johnson Medical School in New Brunswick, New Jersey. "The impact of sleep apnea, however, on carbohydrate craving among diabetics has not been extensively studied, especially in a real-world setting," he explained. "Studies have shown that sleep apnea can worsen diabetes but self-reported carbohydrate craving among this group has not been examined." The study involved 55 adults with a mean age of 62.5 years; 43% were men. The researchers assessed the risk for sleep apnea using the validated Berlin questionnaire, which predicts sleep apnea by incorporating body mass index (BMI), hypertension status, and characterization of snoring and daytime sleepiness. They assessed carbohydrate craving using the Likert scale from 1 (highest) to 5 (lowest). Fifty-four percent of study participants were diabetic, and 82% of these individuals were at high risk for sleep apnea, scoring 2 to 4 on the Berlin questionnaire. Compared with participants without diabetes, the risk for sleep apnea among patients with diabetes was high (odds ratio [OR], 5; 95% confidence interval [CI], 1.8 - 18.9), the researchers found. Further, the diabetic patients had almost double the risk for carbohydrate craving as their nondiabetic counterparts (33% vs 14%). The odds of moderate to high carbohydrate craving was more than double in all patients at high risk for sleep apnea (Berlin score, 2 - 4) vs those at low risk (Berlin score, 0 - 1). The odds ratio was 2.27 (95% CI, 0.76 - 6.7). "Novel Study" Clete Kushida, MD, PhD, professor and medical director of the Stanford Sleep Medicine Center in Palo Alto, California, and past president of the American Academy of Sleep Medicine, told Medscape Medical News, "This is a fairly novel study in that I don't think carbohydrate craving has been looked at in the context of diabetics and sleep apnea. However, it's a small sample size and requires further study." Dr. Kushida was not involved in the study. In a conference statement, the study's principal investigator, Anthony Cannon, MD, American Diabetes Association regional president for central and southern Pennsylvania and southern New Jersey, said, "Current national guidelines on the management of diabetes need to consider sleep apnea as an independent risk factor more vigorously." "The management of patients with diabetes and or metabolic syndrome based solely on pharmacotherapy, exercise and nutritional modifications without taking into account the risk of sleep apnea may not lead to optimal outcomes for patients suffering from these chronic diseases," Dr. Cannon added. He said, "Clearly, a greater awareness among physicians is needed, as sleep apnea is often undiagnosed by primary care physicians. Public policy can play a key role in the educational awareness of the association between sleep apnea and diabetes among both physicians and patients." The study authors and Dr. Kushida have disclosed no relevant financial relationships. SLEEP 2012: Associated Professional Sleep Societies 26th Annual Meeting. Abstract #0912. Presented June 13, 2012

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Gene May Link Diabetes and Alzheimer’s

In recent years it became clear that people with diabetes face an ominous prospect – a far greater risk of developing Alzheimer’s disease. Now researchers at The City College of New York (CCNY) have shed light on one reason why. Biology Professor Chris Li and her colleagues have discovered that a single gene forms a common link between the two diseases. They found that the gene, known to be present in many Alzheimer’s disease cases, affects the insulin pathway. Disruption of this pathway is a hallmark of diabetes. The finding could point to a therapeutic target for both diseases. The researchers report their finding in the June 2012 issue of the journal Genetics. "People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy," said Professor Li, explaining why the link is not far-fetched. Although the cause of Alzheimer’s is still unclear, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients’ brains. Mutations in the human "amyloid precursor protein" (APP) gene, or in genes that process APP, show up in cases of Alzheimer’s that run in families. In the study, Professor Li and her colleagues scrutinized a protein called APL-1, made by a gene in the worm Caenorhabditis elegans (C. elegans ) that happens to be a perfect stand-in for the human Alzheimer’s disease gene. "What we found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted," said Professor Li. "We began to examine how the worm-equivalent of APP modulated different metabolic pathways and found that the APP equivalent inhibited the insulin pathway." This suggested that the human version of the gene likely plays a role in both Alzheimer’s disease and diabetes. They also found that additional mutations in the insulin pathway reversed the defects of the APP mutation. This helped explain how these genes are functionally linked. The APL-1 is so important, they found, that “when you knock out the worm-equivalent of APP, the animals die," Li explained. “This tells us that the APP family of proteins is essential in worms, as they are essential in mammals,” like us. Professor Li and her colleagues hope that this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer’s disease and diabetes. "This is an important discovery, especially as it comes on the heels of the U.S. government’s new commitment to treat and prevent Alzheimer’s disease by 2025," said Dr. Mark Johnston, editor-in-chief of "Genetics." "We know there’s a link between Alzheimer’s and diabetes, but until now, it was somewhat of a mystery. This finding could open new doors for treating and preventing both diseases." The research has identified one link in the chain, an Alzheimer's disease-related protein to the insulin pathway. This may provide insights into why type II diabetes patients are at higher risk for Alzheimer's. However, the protein fragments into many parts, each of which may attach to and signal neurons and other cells along the way. "The big question," said Professor Li, “Is how the amyloid precursor protein and its cleavage products intersect with the insulin pathway.” Each intersection offers a possible target for drugs and other treatment. Professor Li plans to continue down the pathway, mapping its crossroads as she goes. Source: City College of New York

Goodbye Prostate Cancer

 How do you know when your new cancer drug is working better than expected? When they shut down the clinical trial so that every participating patient can receive it.

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Study: 'Smart bomb' drug attacks breast cancer

Doctors have successfully dropped the first "smart bomb" on breast cancer, using a drug to deliver a toxic payload to tumor cells while leaving healthy ones alone.

In a key test involving nearly 1,000 women with very advanced disease, the experimental treatment extended by several months the time women lived without their cancer getting worse, doctors planned to report Sunday at a cancer conference in Chicago.

More importantly, the treatment seems likely to improve survival; it will take more time to know for sure. After two years, 65 percent of women who received it were still alive versus 47 percent of those in a comparison group given two standard cancer drugs.

That margin fell just short of the very strict criteria researchers set for stopping the study and declaring the new treatment a winner, and they hope the benefit becomes more clear with time. In fact, so many women on the new treatment are still alive that researchers cannot yet determine average survival for the group.

"The absolute difference is greater than one year in how long these people live," said the study's leader, Dr. Kimberly Blackwell of Duke University. "This is a major step forward."

A warning to hopeful patients: the drug is still experimental, so not available yet. Its backers hope it can reach the market within a year.

The treatment builds on Herceptin, the first gene-targeted therapy for breast cancer. It is used for about 20 percent of patients whose tumors overproduce a certain protein.

Researchers combined Herceptin with a chemotherapy so toxic that it can't be given by itself, plus a chemical to keep the two linked until they reach a cancer cell where the poison can be released to kill it.

This double weapon, called T-DM1, is the "smart bomb," although it's actually not all that smart — Herceptin isn't a homing device, just a substance that binds to breast cancer cells once it encounters them.

Doctors tested T-DM1 in 991 women with widely spread breast cancer that was getting worse despite treatment with chemotherapy and ordinary Herceptin. They were given either T-DM1 infusions every three weeks or infusions of Xeloda plus daily Tykerb pills — the only other treatments approved for such cases.

The median time until cancer got worse was nearly 10 months in the women given T-DM1 versus just over 6 months for the others. That is about the same magnitude of benefit initially seen with Herceptin, which later proved to improve overall survival, too, Blackwell said.

T-DM1 caused fewer side effects than the other drugs did. Some women on T-DM1 had signs of liver damage and low levels of factors that help blood clot, but most did not have the usual problems of chemotherapy.

"People don't lose their hair, they don't throw up. They don't need nausea medicines, they don't need transfusions," said Blackwell, who has consulted in the past for Genentech, the study's sponsor.

"The data are pretty compelling," said Dr. Michael Link, a pediatric cancer specialist at Stanford University who is president of the American Society of Clinical Oncology, the group hosting the Chicago conference where the results were being presented.

"It's sort of a smart bomb kind of therapy, a poison delivered to the tumor ... and not a lot of other collateral damage to other organs," he said.

Dr. Louis Weiner, director of Georgetown Lombardi Comprehensive Cancer Center, said the results strongly suggest T-DM1 improves survival. It delivers more drug directly to tumors with less side effects, "a clear advance," he said.

Denise Davis, 51, a customer service representative at a propane company, was diagnosed three years ago with breast cancer that had spread to her liver and bones. Since February of last year, the Lynchburg, Va., woman has made the two-hour trip to Duke in Durham, N.C., every three weeks to get infusions of T-DM1.

"I call it 'Herceptin-plus,'" she said. Scans every six weeks show "everything is still shrinking or stable," she said. "Right now, I'm feeling pretty good about it. The only way I'd feel a little better is if it took care of everything, but I'll take what I can get."

Genentech, part of the Swiss company Roche, plans to seek approval later this year to sell the drug in Europe and the United States. Another company, ImmunoGen Inc., made the technology combining the drugs.

Genentech says the price of T-DM1 has not been determined. Herceptin costs more than $4,000 a month plus whatever doctors charge to infuse it. Herceptin's U.S. patent doesn't expire until 2019.