The Gene Pool is Getting Murky

February 2nd, 2012 No comments »

Copyright New York Times

Researchers have now found an entirely new line of ancestors of modern humans  - the Denisovans- whose genes we carry.  Gains in DNA Are Speeding Research Into Human Origins – NYTimes.com The article contains speculation that the mating between different early humans allowed for the transfer of genes helping the immune system. However, the archaic immune genetic material may be responsible for autoimmune diseases such as multiple sclerosis, arthritis and diabetes.

Why mention this? The point is that whenever someone mentions the influence of genetics of obesity, the common retort is that ‘the gene pool doesn’t change so fast.” The problems with this answer are (a) as indicated by the above study we are still sorting out what exactly is in the gene pool, (b) it ignores other recent findings showing that there are changes occurring more recently in our genes, (c) it ignores the long, 300 year picture of increasing height and weight in humans, and (d) it ignores the strong, developing evidence of the intrauterine environment and epigenetics.

Further evidence has just come out in a study of obesity across three generations. The researchers found that BMI is highly transmissible across generations, and especially involving the maternal line. The fundamental link between BMI of mother and child was not explained by shared environmental factors alone. Both mothers and fathers contribute equally to the child’s height. This was a prospective study with data collected from 3 generations of one family, with data taken prior to pregnancy and in early childhood. The authors conclude, “BMI in early childhood may be transmitted through a combination of genetic and intrauterine effects possibly operating via epigenetic mechanisms”.  Body mass index and height over three gene… [BMC Public Health. 2012] – PubMed – NCBI

 

Powerful New Study Underscores Obesity-Pain Relationship

January 28th, 2012 No comments »

A new survey of one million Americans found a high association between obesity and pain. Obesity and Pain Are Associated in t… [Obesity (Silver Spring). 2012] – PubMed – NCBIThey found the association was “robust” among both men and women. This survey involved an unusually high number of subjects and confirmed earlier studies.

New View on the Origins of Our Obesity Predicament

December 24th, 2011 No comments »

As readers know, there is a certain disconnect about when the obesity    epidemic began. Personally, I am quite persuaded that the historical record for the increase in human weight and height (the two parts of the BMI formula) goes back at least 350 years. (See, The Techno-physiological Revolution). On the other hand, something seemed to happened in the United States around the 1970s to send the rates skyward. There are no end of theories, all of which have some plausibility. So now comes Melinda Sothern, a well-respected and highly published obesity researcher, with a new look at mothers in the 1950’s. (Ouch! That’s a little close to home.) Her thoughts in this article do meet up with current research on genetic and, especially, epigenetic factors influencing the development of obesity. 

Many knowledgeable researchers have avoided going into this territory, not because of the science but because of the fear of being blamed for blaming mothers. This is not an inconsequential factor as parents may defer medical care for fear of being blamed for their child’s weight problems. (See the Cleveland obese boy incident.)

Sothern’s experiences and scientific credibility gives impetus to seriously consider her thoughts on the origin of our current predicament, given in this article in The Republic, ’50s women may have triggered obesity epidemic | The Republic

Below the Radar

December 23rd, 2011 No comments »

Before leaving for his holiday in Hawaii, President Barack Obama signed the appropriations bill to keep the government running. Included in the bill is a provision establishing the National Center for Advancing Translational Sciences (NCATS). This center is the brainchild of NIH Director Francis Collins. Statement by NIH Director Dr. Francis Collins – NIH Launches National Center for Advancing Translational Sciences, December 23, 2011 – The NIH Director – National Institutes of Health (NIH) It is intended to develop resources at NIH to facilitate moving basic biomedical research into treatments and removing roadblocks to incorporating new findings into patient care. Off the record, NIH officials are concerned that one of the bigger roadblocks is the failure of new drugs to gain approval by the Food and Drug Administration. Obviously, this includes drugs to treat obesity. While addressing this specific issue is not part of the NCATS mission, it clearly provides a platform to move in this direction. The very first activity of this center is a collaboration with FDA and DARPA to develop a chip to screen new drugs for toxicity. NIH, DARPA and FDA collaborate to develop cutting-edge technologies to predict drug safety, September 16, 2011 News Release – National Institutes of Health (NIH)

As it happens, my paper on the FDA approval process, written with colleagues,] Christopher Still and Arya Sharma, specifically called for a NIH-FDA-industry-patient group collaboration to find ways to overcome obstacles to the approval of drugs to treat obesity. What’s Up with the FDA – Part 5 | The Downey Obesity Report

So, keep an eye on NCATS. It may become very important and relevant to advancing the treatment of obesity. Proposed NCATS « Feedback NIH

Genetics and Treatments

December 20th, 2011 No comments »

The Diabetes Prevention Program (DPP) is regarded as a hallmark of behavioral intervention in the treatment of adult obesity. Now comes a paper from the DPP Study Group, as well as drug therapy via metformin. It recognizes that genetic factors affect the success of participants in achieving and maintain weight loss. Genetic Predictors of Weight Loss and Weight R… [Diabetes Care. 2011] – PubMed – NCBI

Gingrich Gets Brain Science Politics Wrong

December 15th, 2011 No comments »

In a Washington Post blog, Gingrich at University of Iowa: ‘I want to talk to you about brain science’ – Election 2012 – The Washington Post, Presidential candidate Newt Gingrich is quoted as saying,  “This (brain science)  is a very big idea in an area that many political leaders won’t attack.” Well, I spent most of the 1990s dealing with neuroscience research funding in Congress and there were many political leaders willing to support (as opposed to “attack”) neuroscience research.

I responded with this comment, “Gingrich has got it all wrong on the politics of neuroscience. In fact, many politicians have embraced it, going back to the 1980s, when the late Congressman Silvio Conte (R-MA), led the efforts on the Appropriations Committee to expand neuroscience research funding, principally at the National Institutes of Health. He also introduced and led enactment by Congress of the Decade of the Brain Resolution which President George Bush (41) signed, declaring the 1990s as “The Decade of the Bran.” There were numerous Congressional briefings and events during the 90s, some sponsored by the Library of Congress, and many by patient and professional groups as well as organizations I was associated with, such as the National Foundation for Brain Research. Congressman Claude Pepper, Senators Pete Domenici, Tom Harkin, Ted Kennedy, and Lowell Weicker were outstanding leaders. Gingrich was not one of them although to be fair he did support expansion of NIH funding overall.”

The blog also had a reference which seemed to indicated that someone was complaining about the lack of action by the FDA to approve anti-obesity drugs. However, the question appeared to pit obesity against neurology. My response, There is a curious reference in the blog, seemingly from a member of the audience, on whether obesity should be stressed over neurology. The question is odd. Obesity is a neuro-endocrine disease and the brain plays a critical, actually the critical, role in regulating body weight. So, one can’t really posit obesity or neurology. This is not to say all treatments have to be neurological. Many, like lap-band or the OTC drug, Alli, do not work on the neurological system.”

As readers have seen, obesity is playing a prominent role in this campaign so far. See Politics. Take the opportunity to comment on news articles such as this one to set the record straight.

New Insight in Obesity Progression

November 4th, 2011 No comments »

Every now and then a study appears and you realize no one has ever done this before. Here’s one which may have profound impact.  A group from Kings College London looked at 1,000 women aged 45-68 years who were annually checked for BMI. Now, at this point, most studies would report the mean or average BMI. But they went further. They looked at each individual’s weight trajectory, i.e. did their weight change or stay the same. What they found was a great stability in individual BMI during the years of follow-up. 30% had no change in their weight. Nonetheless, weight increased in 58%, decreased in 11.4%. The authors note that simply combining all individuals into groups and overlooking the distinctive patterns of BMI change may lead to biased inferences in epidemiologic and etiologic research in the future. Longitudinal study of variation in body mass ind… [Age (Dordr). 2011] – PubMed – NCBI

 I have been sending this paper to a number of researchers, suggesting they look at databases available to them, such as the placebo arms of intervention studies, to replicate this study. If it is replicated, it may have a great effect on future clinical trials. The authors of the paper call for an examination of genetic polymorphisms according to this weight paradigm. This might mean that future clinical trials might be able to exclude those expected to naturally lose weight and concentrate on those likely to gain weight. This may be doubly important if the FDA requires more studies of cardiovascular endpoints. Such studies, like the SCOUT trial, necessitate an older population, some of whom, it appears, are losing weight naturally.

Cancer and Obesity Explored

November 3rd, 2011 No comments »

The Institute of Medicine’s National Cancer Policy Forum this week convened a two-day workshop, “The Role of Obesity in Cancer Survival and Recurrance.” So this is a good opportunity to re-visit the relationship between these two deadly diseases. Susan Gapstur of the American Cancer Society noted the growing list of cancers associated with obesity. For men, these include cancers of the colon, esophagus, kidney, colorectum, pancreas, gallbladder and liver. Women are affected by the same cancers as well as of the endometrium and postmenopausal breast cancer. Evidence is accumulating for an association with non-Hodgkin’s lymphoma, ovarian cancer in women and aggressive prostate in men. Obesity, she pointed out, is not the second (to tobacco) leading risk factor of cancer. Ominously, she pointed out we do not know what the health effects will be for the children now obesity who will obese for a lifetime.

Pamela J. Goodwin of the University of Toronto explored potential mechanisms in the progression to cancer including inflammation, adipokines, hyperinsulinemia, diabetes/diabetes drugs and sex steroids. She pointed to studies showing reductions in cancer risk with intentional weight loss of 20 pounds or more. Intentional weight loss and in… [Int J Obes Relat Metab Disord. 2003] – PubMed – NCBI and reduction in the relative risks of death and of cancer following bariatric surgery. Metabolic surgery and cancer: protective effects of b… [Cancer. 2011] – PubMed – NCBI.  Specifically, she showed the positive effect of intentional weight loss on breast cancer risk   Does intentional weight loss reduce canc… [Diabetes Obes Metab. 2011] – PubMed – NCBI and the impact of physical activity on improvements in insulin in breast cancer survivors Impact of a mixed strength and endurance exerci… [J Clin Oncol. 2008] – PubMed – NCBI.

Bruce Wolfe of the Oregon and Science University and a bariatric surgeon reminded the participants that the Swedish Obesity Study found the reduction in mortality after bariatric surgery was greater for cancer than for cardiovascular events Effects of bariatric surgery on mortality in Sw… [N Engl J Med. 2007] – PubMed – NCBI. In a Utah study, bariatric surgery reduced deaths from cancer by 60% compared to a 48% reduction in cardiovascular events. Long-term mortality after gastric bypass surgery. [N Engl J Med. 2007] – PubMed – NCBI

Rachel Ballard-Barbash of the National Cancer Institute, who has been a leader in exploring the obesity-cancer connection for many years, moved the discussion to look at the co-morbid conditions of obesity and their relationship to cancer mortality, including renal disease, congestive heart failure, cerebrovascular disease, citing A refined comorbidity measurement algorithm fo… [Ann Epidemiol. 2007] – PubMed – NCBI

Patricia Ganz of the UCLA Schools of Medicine picked up the point and explained that about half of all deaths of breast cancer survivors are due to causes other than breast cancer. She recommended prevention of weight gain and/or weight loss in those breast cancer survivors who are obese. 

Thomas Wadden described the non-surgical approaches to weight loss used in the Diabetes Prevention Program and the LOOK Ahead study and the contribution of intensive behavioral counseling to reduction in comorbid conditions associated with obesity

Some of the workshop’s presentations are on-line at Workshop on the Role of Obesity in Cancer Survival and Recurrence – Institute of Medicine. Watch that site for future information on a publication from the workshop.