Health for life

Researchers at the Linda Crnic Institute for Down Syndrome and the University of Colorado School of Medicine have found that a single mechanism may underlie the damaging effect of cholesterol on the brain and on blood vessels.

High levels of blood cholesterol increase the risk of both Alzheimers disease and heart disease, but it has been unclear exactly how cholesterol damages the brain to promote Alzheimers disease and blood vessels to promote atherosclerosis.

Using insights gained from studying two much rarer disorders, Down Syndrome and Niemann Pick-C disease, researchers at the Linda Crnic Institute for Down Syndrome and the Department of Neurology of the University of Colorado School of Medicine found that cholesterol wreaks havoc on the orderly process of cell division, leading to defective daughter cells throughout the body.

In the new study published this week in the on-line journal PLOS ONE, Antoneta Granic, PhD, and Huntington Potter, PhD, show that cholesterol, particularly in the LDL form, called bad cholesterol, causes cells in both humans and mice to divide incorrectly and distribute their already-duplicated chromosomes unequally to the next generation. The result is an accumulation of defective daughter cells with the wrong number of chromosomes and theore the wrong number of genes. Instead of the correct two copies of each chromosome, and thus two copies of each gene, some cells acquired three copies and some only one.

Granic and Potters study of the effects of cholesterol on cell division included a prominent finding of cells carrying three copies of the chromosome (#21 in humans and #16 in mice) that encodes the amyloid peptide that is the key component of the neurotoxic amyloid filaments that accumulate in the brains of Alzheimer patients.

Human trisomy 21 cells are significant because people with Down syndrome have trisomy 21 in all of their cells from the moment of conception, and they all develop the brain pathology and many develop the dementia of Alzheimers disease by age 50. Earlier studies by Granic, Potter and others have shown that as many as 10% of cells in an Alzheimer patient, including neurons in the brain, have three copies of chromosome 21 instead of the usual two. Thus, Alzheimers disease is, in some ways, a form of acquired Down syndrome. Furthermore, mutant genes that cause inherited Alzheimers disease cause the same defect in chromosome segregation as does cholesterol, thus indicating the presence of a common cell division problem in both familial and sporadic (non-familial) Alzheimers disease.

The new research also found trisomy 21 neurons in the brains of children with what, until now, was thought to be an unrelated neurodegenerative disease (Niemann Pick type C), caused by a mutation affecting cholesterol physiology. This result suggests that neurodegeneration itself might be linked to chromosome missegregation.

Such a model is supported by the finding of Thomas Arendt, MD, and colleagues at the University of Leipzig that 90% of the neuronal cell death observed at autopsy in Alzheimer patients is due to the creation and selective loss of neurons with the wrong number of chromosomes.

Identifying the specific problem caused by cholesterol will lead to completely new approaches to therapy for many human diseases, including Alzheimers disease, atherosclerosis and possibly cancer, all of which show signs of defective cell division. Granic and Potter already have found a potentially simple approach to preventing cholesterol from causing cells to distribute their chromosomes unequally into their new daughter cells. Specifically, when cells in culture were first treated with ethanol, the subsequent exposure to bad cholesterol was without effect on cell division: Each daughter cell received the correct number of chromosomes.

A wealth of research is pointing to an ever increasing problem that is shown to increase our risk of cancer, as well as a host of other genetically influenced illnesses. The problem is with light sources in the bedroom at night when most people are asleep.

Postmenopausal women who consumed sugar-sweetened beverages were more likely to develop the most common type of endometrial cancer compared with women who did not drink sugar-sweetened beverages, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Postmenopausal women who reported the highest intake of sugar-sweetened beverages had a 78 percent increased risk for estrogen-dependent type I endometrial cancer (the most common type of this disease). This association was found in a dose-dependent manner: the more sugar-sweetened beverages a woman drank, the higher her risk.

"Although ours is the first study to show this relationship, it is not surprising to see that women who drank more sugar-sweetened beverages had a higher risk of estrogen-dependent type I endometrial cancer but not estrogen-independent type II endometrial cancer," said Maki Inoue-Choi, Ph.D., M.S., R.D., who led this study as a research associate in the Division of Epidemiology and Community Health of the University of Minnesota School of Public Health in Minneapolis. "Other studies have shown increasing consumption of sugar-sweetened beverages has paralleled the increase in obesity. Obese women tend to have higher levels of estrogens and insulin than women of normal weight. Increased levels of estrogens and insulin are established risk factors for endometrial cancer."

Because this study is the first to show the association between high sugar-sweetened beverage consumption and endometrial cancer, such findings need replication in other studies, according to Inoue-Choi.

Inoue-Choi and colleagues used data from 23,039 postmenopausal women who reported dietary intake, demographic information, and medical history in 1986, prior to the cancer diagnosis, as part of the Iowa Womens Health Study.

Dietary intake was assessed using the Harvard Food Frequency Questionnaire (FFQ), which asked study participants to report intake frequency of 127 food items in the previous 12 months. A typical portion size for each food item was provided to give study participants a sense of scale.

As reported in the study, the FFQ included four questions asking usual intake frequency of sugar-sweetened beverages, including 1) Coke®, Pepsi®, or other colas with sugar; 2) caffeine-free Coke®, Pepsi®, or other colas with sugar; 3) other carbonated beverages with sugar (e.g., 7-Up®); and 4) Hawaiian Punch®, lemonade, or other noncarbonated fruit drinks.

"Sugar-free soft drinks" included low-calorie caffeinated and caffeine-free cola (e.g., Pepsi-Free®), and other low-calorie carbonated beverages (e.g., Fresca®, Diet 7-Up®, and Diet Ginger Ale®).

The "sweets and baked goods" category comprised 13 items in the FFQ, including chocolate, candy bars, candy without chocolate, cookies (home-baked and ready-made), brownies, doughnuts, cakes (home-baked and ready-made), sweet rolls, coffeecakes or other pastries (home-baked and ready-made), and pies (home-baked and ready-made).

The researchers categorized the sugar-sweetened beverage consumption patterns of these women into quintiles, ranging from no intake (the lowest quintile) to between 1.7 and 60.5 servings a week (the highest quintile).

Between 1986 and 2010, 506 type I and 89 type II endometrial cancers were recorded among the women Inoue-Choi and colleagues studied. They did not find any association between type I or type II endometrial cancers and consumption of sugar-free soft drinks, sweets/baked goods, and starch.

"Research has documented the contribution of sugar-sweetened beverages to the obesity epidemic," said Inoue-Choi. "Too much added sugar can boost a persons overall calorie intake and may increase the risk of health conditions such as obesity, diabetes, heart disease, and cancer."

"Hi doc! I used my on-line portal to make an appointment!"

Hey there Accountable Care Organization executive.

Youre probably willing to continue to commit millions of dollars toward an electronic health record (EHR) coupled to an online patient portal.  Thats because youve been told by your leadership team that electronic consumer empowerment, patient-provider communication and the substitution of efficient two-way messaging for costly face-to-face visits will increase quality, reduce expenses, generate shared savings and guarantee that your life-sized portrait will be prominently displayed in your flagship hospitals lobby.

Well, after youve read a just-published JAMA research study by Ted Palen, Colleen Ross, David Powers and Stanley Xu, you may want to tell your administrative assistant to cancel that appointment with the portrait artist.

The articles title is Association of Online Patient Access to Clinicians and Medical Records With Use of Clinical Services.

How the study was done:

Kaiser Permanente Colorado added "MyHealthManager" (MHM) to their EHR in May 2006. MHM allows patients to view tests, records, problem lists as well as care plans, schedule appointments, request ills and message their doctors. By June of 2009, over 375,000 Kaiser patients had signed up for MHM. Of those, about 45% had used the system at least once.  Of this number, Kaiser researchers pulled the records of 44,321 persons who had been continuously enrolled in the Kaiser system for at least two years. 

This group was retrospectively matched to a control group of Kaiser patients who had not signed up for MHM.  The authors did this through "propensity matching." This found a similar number of patients, based on age, gender, race, number of chronic illnesses and baseline office visits who, using logistic regression analytics, appeared to be the type of patient who would otherwise sign up for MHM.

The results:

Compared to non-MHM patients, the MHM experienced an increase in hospitalization rates (20 per thousand patients) and emergency room visits (11 per thousand).  In other words, for every hundred patients, the on-line portal seemed to lead to 2 extra hospitalizations and 1 extra ER visit. Both differences were statistically significant.

There were also increases in the number of office visits (.7 per patient per year), telephone calls (.3 per patient per year) and after-hour clinic visits (18.7 per thousand patients per year).

Caveats:

The authors correctly point out that this study is not perfect.  Retrospective propensity matching is not as good as a randomized clinical trial; its possible that the patients who self-selected for MHM were already realtively more interested in or likely to increase their use of health care services.  Results at Kaiser may not apply elsewhere.

Implications:

Despite the limitations, this study should be a wake-up call for those who believe EHR portals is a savings panacea.  By increasing access to on-line services, physicians and patients may paradoxically use the system to address concerns that otherwise wouldnt come to medical attention.  In other words, the EHR portal exacerbates the classic health care economics problem of supplier-induced demand.

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Two components of red meat — dietary protein and dietary iron — may combine to form powerful carcinogens, N-nitroso compounds, which increase risk for bladder cancer. Moreover, individuals with reduced ability to reverse the effects of N-nitroso compounds because of a genetic variation in their RAD52 gene could be at particularly high risk.

Chelsea Catsburg, a doctoral student at the Keck School of Medicine of the University of Southern California, Los Angeles, presented these data at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held here Oct. 16-19, 2012.

Dietary protein is made up of amino acids, which can be naturally metabolized into biogenic amines, according to Catsburg. Research has shown that the processing and storage of meat increases amine concentrations. When these amines are in the presence of nitrites, they generate nitrosamines, which have carcinogenic properties. In addition, heme iron, found in red meat, has been shown to increase the formation of nitrosamines from amines.

"Nitrosamine formation occurs predominantly in the stomach and intestines, so these exposures have been studied extensively in relation to gastric cancer and somewhat in relation to colorectal cancer," Catsburg said. "However, there is evidence that these reactions also take place in the bladder, particularly in the presence of infection."

Catsburg and colleagues had previously found that meat groups with high heme and high amine concentrations, such as salami and liver, increased risk for bladder cancer. In this study, they examined whether genetic variation in DNA repair enzymes, available to correct the damage caused by these endogenously formed carcinogens, modified these associations.

The researchers tested 627 single-nucleotide polymorphisms in 27 genes involved in N-nitroso compound metabolism or DNA repair. They collected data from 355 bladder cancer cases and 409 controls in the Los Angeles Bladder Cancer Study.

"We found that a polymorphism in the RAD52 gene modified the effect of these exposures," Catsburg said. "This polymorphism is suspected to reduce the DNA repair activity of the RAD52 protein, and the association of these meat groups and bladder cancer risk was significantly higher in individuals with one or more copies of this polymorphism."

These results further support recommendations by the World Cancer Research Fund to limit red meat intake and to avoid processed meats to reduce risk for stomach and bowel cancer, according to the researchers.

"This study suggests that these exposures may also affect secondary organs such as the bladder," Catsburg said. "Individuals at risk for bladder cancer may wish to avoid intake of red and processed meats, especially if they have genetic polymorphisms that reduce DNA repair activity and make them more vulnerable to the effects of carcinogens."

Further replication of this study to support an association between heme and meat intake and the risk for bladder cancer is necessary, she added.

Chronic inflammation appears to play a key role in the development of cancer, along with heart disease and diabetes. Now a new study presented today suggests that eating a diet high in sugar, saturated fats and others foods that promote inflammation increases the risk of premature death from any cause, including cancers of the gastrointestinal tract.

The study was one of the approximately 130 poster presentations featured at the American Institute for Cancer Research (AICR) Annual Research Conference.

Study researchers used an inflammatory index of foods and nutrients developed by University of South Carolina (USC) researchers.

“Studies have shown that diet can modify inflammation, and inflammation can drive the growth of many cancers, such as colorectal cancer,” says Susan E. Steck, PhD, MPH, RD, USC Associate Professor and co-author of the study. “In previous studies, we found that dietary inflammatory index scores were associated with levels of C-reactive protein, a marker of inflammation.

This new study extends the research to examine disease outcomes, and suggests that consuming fewer pro-inflammatory dietary factors and more anti-inflammatory dietary factors may reduce risk of gastrointestinal tract cancer death.”

The study followed 10,525 men and women in the Aerobics Center Longitudinal Study from 1987 through 2003. Participants had completed three-day food records when the study began.

At the end of the study, 259 people had died; 30 from gastrointestinal tract cancers. Gastrointestinal tract cancers include cancers of the esophagus, stomach, colon and rectum.

Compared to those consuming the most anti-inflammatory diet, participants consuming the most pro-inflammatory diet had a 53 percent higher risk of mortality during the course of the study. (The risk slightly decreased after adjusting for cardiorespiratory fitness.)

For gastrointestinal tract cancers, there was a four-fold increase among the group consuming the most pro-inflammatory diet compared to the most anti-inflammatory.

According to a report issued jointly by the American Diabetes Association and the American Cancer Society, people with diabetes are at a significantly higher risk of certain forms of cancer.^{1, 2}

They are at least twice as likely to get cancer of the liver, pancreas and endometrium. Their risk of colon, breast and bladder cancer is 20 to 50 percent higher than people without diabetes.

Just how diabetes (primarily type 2 diabetes) increases cancer risk is not well understood. (It should be said ... the etiology of type 2 diabetes is not completely understood either.) Current thinking includes:

• Shared risk factors such as poor diet, smoking, inactivity, and obesity.
  
• Exposure to higher levels or insulin and blood glucose, either of which may promote cancer growth.
  
• Diabetes characteristics such as insulin resistance and chronic inflammation.
  
• Multidrug therapy for diabetes treatment.

People with diabetes and their healthcare providers should be attentive to changes that may indicate early signs of cancer.
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¹ Diabetes and Cancer: A Consensus Report, CA: A Cancer Journal for Clinicians, June 2010
² Mysterious Link Connects Diabetes And Cancer, NPR, June 2010

A new study in Diabetes Care found that eating eggs may raise the risk for developing type 2 diabetes:¹

"These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women."

The data came from two large cohorts, the Physicians Health Study I (1982–2007) that included 20,703 men, and the Womens Health Study (1992–2007) that included 36,295 women.

Men experienced an increased risk for diabetes of:

• 18% for 2-4 eggs/week
  
• 46% for 5-6 eggs/week
  
• 58% for 7 or more eggs/week

Women experienced an increased risk for diabetes of:

• 19% for 2-4 eggs/week
  
• 18% for 5-6 eggs/week
  
• 77% for 7 or more eggs/week

An earlier study from May of this year that used the same Physicians Health Study I cohort found that men who ate more eggs had a higher risk of dying during a 20-year follow-up than men who ate fewer eggs. For men who also had diabetes, the increased risk rose from 25% to 200%.
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¹Egg Consumption and Risk of Type 2 Diabetes in Men and Women, Diabetes Care, published online ahead of print November 18, 2008.