Posts Tagged ‘cardiovascular disease’

Look AHEAD Crashes

October 22nd, 2012


Behind Look Ahead

The National Institutes of Health (NIH) has announced that the Look AHEAD trial has been stopped in its 11th year, two years short of completion. The extensive trial, involving over 5,000 patients at 16 centers, was intended to find out if there was increased mortality from intentional weight loss and to see if intentional weight loss among obese patients with type 2 diabetes would result in fewer cardiovascular (CV) events. At the end of the trial, there was no difference between the study group, which received intensive behavioral counseling and the control group which received standard diabetes education and occasional support group meetings.  The NIH press release indicates that both arms had lower CV rates that reported for patients with diabetes in previous studies. NIHNEWS: Weight Loss Not Reduce CV events in Type 2 diabetes

While this is news is something of a shock, many folks saw it coming. Two years into the trial, which began in 2001, the monitoring board noticed that the event rate in the control arm was much lower than expected. The expected CVD event rate in the control arm was 3.125% per year; in fact it was 0.7%. A committee was formed and made changes to the original study protocol designed to capture more events. These changes went into effect in 2008. There appeared to be three reasons for the lower event rate. First, while cardiovascular disease (CVD) is still the major cause of death in the United States, mortality has gone down, resulting from better control of dyslipidemia and high blood pressure and improved care of chronic and acute coronary syndromes. (See NCHS Data Brief, NCHS DataBrief: Prevalence of Uncontrolled Risk Factors for CVD)  Second, study participants who choose to involve themselves in a long clinical trial may well be healthier than a community sample and more motivated to follow the diet and exercise and participation requirements. Finally, the Look AHEAD trial employed the Graded Exercise Test which excluded participants most likely to develop CVD. Because of the low event rate, an additional primary endpoint was added (hospitalized angina) and the trial was extended for 2 years. (See PubMed: Brancati_Midcourse Correction to clinical trial whe the event rate is underestimated: the Look Ahead Study) Readers may recall that the SCOUT trial of sibutramine also had to revise its protocol midway through the study for the same reason, resulting in a population which was older and sicker than typical clinical population. In both cases, revising the protocol did not favor the intervention.

The stopping of Look AHEAD raises a host of questions. Was the study protocol correct? Did it end up studying healthy obese diabetics? Do long-term studies produce more noise than insight? Are we really studying the aging process when we cannot control for changes in health status, drug utilization (including drugs which can increase weight) and changes in energy intake, fitness levels, etc.? What is the picture for sub-groups, such as the 60-74 age group which had good weight loss in the DPP and 4 year results of Look AHEAD? Were there specific improvements, such as reductions in medications usage, fewer hospitalizations or shorter length of stays, improvements in quality of life? Did the presence of any the alleles associated with success in bariatric surgery affect outcomes? PubMed: High allelic burden of four obesity SNPs associated with poorer wt loss.  Should future efforts be devoted to cases where the disease process is already well-established or where high-risk populations can be identified and appropriate interventions evaluated? In future trials, should comorbid management be left to the local standards of care or defined in the study protocol?

Looking Ahead of Look Ahead

Whither behavioral lifestyle interventions?

The lifestyle interventions in the DPP and Look AHEAD were regarded as the ‘gold standard.’ They involved recruiting and training health professionals who provided not only the intervention but provided a supportive environment and a community spirit. Extensive communication with the patient was maintained. PUBMED: Look AHEAD: Description of the Lifestyle Intervention. Look AHEAD  participants even received an honoraria of $100 at each annual visit to improve adherence. (FDA EMDAC Hearing, March 28, 2012, Dr. Rena Wing, transcript, p. 169).

Recently the CDC and the NIH were looking at ways to take the DPP/Look AHEAD model to a more replicable model. The CDC’s National DPP program awarded $6.75 million in grants to develop lifestyle interventions program among people at high risk. One involves using the YMCA to provide lifestyle counseling. Questions will certainly be asked if highly trained professionals with incentives for participants did not produce better results will a down-scale program do better?

Whither diabetes prevention?

Look AHEAD was designed following the Diabetes Prevention Program (DPP). The DPP established that both lifestyle changes and metformin could reduce the incidence of type 2 diabetes, through weight loss, although lifestyle was superior to metformin alone. Look AHEAD was taking this important finding one step further asking whether weight loss among type 2 diabetics would reduce the incidence of cardiovascular events.

Even though the DPP has been promoted as a model for preventing the development of type 2 diabetes through weight loss, there were problems.

Dr. William Knowler of the National Institute on Diabetes, Digestive, and Kidney Disease (NIDDK) told the FDA Advisory Committee earlier this year,that, after three years of the DPP,

“the rates (of development of type 2 diabetes) have tended to flatten out and become parallel among all three groups. The rate of new development of diabetes has actually slowed down in the placebo and metformin groups, compared to what it was in the first three years. And the lifestyle group has flattened out a little bit at the end, but the difference that was attained has been largely maintained over time.  Notice, though, that over 10 years, although there still are remarkable treatment effects, if you look at things in an absolute sense, we can’t say that we still know how to prevent diabetes because, still, close to half of the people who enrolled in the trial developed diabetes over a 10-year period. But at least it’s been substantially delayed in those who have had the interventions.” ( FDA Endocrinologic and Metabolic Drug Advisory Committee Hearing on assessing cardiovascular safety of obesity drugs, March 28, 2012, Transcript, p 131-2).

(Figure: Diabetes Prevention Program Outcomes Study, Lancet (2009) 374; 1677-1686)

Is ‘delaying’ diabetes onset as powerful as ‘preventing’ diabetes from occurring in the competitive race for health care dollars and public attention?

Furthermore, a study earlier this year indicate poor outcomes in drug treatment of adolescents with type 2 diabetes with barely half showing glycemic control with metformin. PubMed: Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes

Will the Look AHEAD experience affect FDA approval of drugs and devices to treat obesity?

The FDA has viewed obesity as a cosmetic issue and only recently acknowledged it as a disease, worthy of attention as other cardiovascular risk factors. They (meaning the FDA Endocrinologic and Metabolic Drug Advisory Committee and FDA staff) have started, just barely, to view obesity as a cardiovascular disease risk factor, like hypertension. They have also opined, from time to time, that if folks only ate less and exercised more, they would not need drugs. So how does this decision play into these views? On one hand, they may be convinced that obesity is not so easy to treat as they thought by diet and exercise. On the other hand, they may think that there is less need for anti-obesity medications because other treatments, e.g. statins, lipid-lowering drugs, anti-hypertensives, are doing their job in reducing CV risk factors. So, this view may raise the bar for approval of new anti-obesity medications. On the other (the third?) hand, we may need a re-definition of obesity which tones down its “diabetes-metabolic syndrome-mortality” axis and raises its “disability-mobility-quality of life” axis. (Running out of hands here, I would not underestimate the potential for greater evidence of obesity’s role in the development of various cancers).

The recent trend in thinking at the FDA Endocrinologic and Metabolic Drug Advisory Committee (EMDAC) has been to view anti-obesity medications narrowly as cardiovascular disease treatments. The EMDAC met on March 28th and 29th,2012  and discussed how to assess the cardiovascular benefits and safety of anti-obesity medications. At the end of March 28, Dr. Rasmussen, who is the Industry Representative on the committee had the following exchange with Dr. Eric Coleman of the FDA.

Dr. Rasmussen: In your (Dr. Colman’s) presentation, you showed that there are different            populations pre-approval and in post-approval studies. ..Are we compromising the risk-            benefit evaluation if we impose more risk-based patients pre-approval?

Dr. Colman: I’m not sure I understood your question. Could you rephrase it?

Dr. Rasmussen: Maybe I’m preempting some of the discussion that we’ll be having                        tomorrow, whether we should require more high-risk CV patients pre-approval to rule out        a upper bound of the 95 percent confidence interval. But by doing so, we will likely be                including older patients with established cardiovascular risk disease. And I’m wondering          whether including more of those types of patients will compromise the benefits side of                doing the benefit-risk evaluation.

Dr. Coleman: Yes. And it might be that if the program had the resources to do this, that              that would just be one component of the program, and that there would be other be other,        smaller, shorter-term studies where they could study lower-risk individuals, younger                   individuals for shorter periods of time.

Dr. Rasmussen: But my concern was based on the fact that the SCOUT study didn’t really – I      mean, it looks like it wouldn’t be actually be able to be approved if it was submitted pre-            approval. ..(FDA EMDAC, March 28, 2012, transcript at p. 334-5)

On the second day of the hearing, Dr. Rasmussen returned to the topic.

Dr. Rasmussen: So I would just like to add a little bit of perspective on what “enrichment”          (Editor: “enrichment” is the term used here by the FDA referring to adding persons at high        risk of CVD to the pool of subjects in obesity drug trials) in this context will mean. I mean, I      did a little bit of “back-of-the-envelope” calculation, and maybe we’ll have that confirmed        after lunch. But, I mean, current programs, approximately 3,000 patient-years of                        exposure generate 15 MACE events or so. Even if we were to double that patient-year                  exposure with a population of a 3-percent annual event rate coming to additional 60                    events, we would still only be able to exclude a doubling of the hazard ratio. So, I mean,              what we’re talking about here is actually completely shifting the population that we’re                going to study in obesity programs to establish cardiovascular disease and not necessarily        the population that we know actually seek treatment in the real world. So, I think that’s              worth keeping in mind, that enrichment may sound appealing because it sounds like we will       add a fraction of sick patients, but in reality, this will be a complete shift of the population.        (FDA, EMDAC, March 29, 2012, at p. 169)

(Dr. Rasmussen’s calculations appear correction. The cardiovascular safety trial the FDA asked Orexigen Therapeutics to undertake surpassed its original goal of 7,000 patients in process of enrolling 9,000 patients to find 87 major CV events earlier than expected. Orexigen: Press Release Contrave CV study.)

A bit later, Dr. Rena Wing was asked about the influence of statins on the Look AHEAD trial. She responded:

Number one, that more and more people are being treated with statins. There’s better                blood sugar control. There’s better hypertension control. So you’re going to have to look          at what’s going to happen to the event rates in these studies. I was very surprised that your      event rates that you’re showing me in many of these trials looked so high compared to the        event rates we’re seeing in Look AHEAD. Now, some of that is because we did do GXTs.                (Editor: Graded Exercise Tests.) We did select healthier patients. But I also think that if you      are doing trials, in the United States especially, and with diabetics where there’s more and        more emphasis on increasing the use of lipids, increasing their blood pressure control, that      you’re going to be driving down your risk factors, and you’re going to have more and more      confounds with medication. (FDA, EMDAC, March 29, 2012 transcript, at p. 346)

At the Cleveland Clinic’s Obesity Summit earlier this month, I asked cardiologist Steve Nissen about the FDA’s pushing companies to undertake clinical trials to rule out a CVD risk. He responded that one of the challenges of cardiovascular outcome studies of obesity drugs is that in order to get enough cv events you have to study patients with existing heart disease or at very high risk of a cv event . This pushes the trial into populations which are considerably sicker than the population likely to take the obesity drug. He suggested that FDA should look at absolute risk rather than the relative risk of the drug. If one looks at the absolute risk, you can study any reasonable population likely to take the drug. This change in the statistical approach allows one to study more typical populations.


In any event, it will be sometime before we know how the newer anti-obesity medications, like Contrave if approved), Belviq™ and Qysemia™ will impact cardiovascular disease risk factors.

Bariatric Surgery: Last Man Standing?

A study out of the Cleveland Clinic published in the New England Journal of Medicine in April, 2012 followed over 90% of 150 patients for 12 months. The study, a face to face comparison of medical therapy versus surgery in patients with uncontrolled type 2 diabetes, showed a clear superiority for bariatric surgery.  The proportion of patients achieving a hemoglobin A1c level of 6% after 12 months by medical therapy alone was 12%; for those in the medical plus gastric bypass surgical group it was 42% and for the medical plus sleeve-gastrectomy group it was 37%. Weight loss was greater in the gastric bypass group (-24kg) and sleeve gastretcomy group (-25.1kg) than in the medical therapy group (-5.4kg). Use of drugs for glucose control, lipids and blood pressure control decreased in the surgical group but increased in the medical group. PubMed: Bariatric surgery versus intensive medical therapy in obese patients with diabetes

In regard to cardiovascular risk factors, a systematic review of the literature on bariatric surgery analyzed over 60 studies involving 19,543 patients. At baseline, the mean patient was 41.7 years old, female and had a BMI of 47.1. Baseline prevalence of comorbid conditions which increase risk of CVD was hypertension (44.4%), diabetes (24%) and hyperlipidemia (43.6%). After correcting for publication bias, 36% of subjects had improvements in hypertension, 26% for diabetes and 34% for hyperlipidemia. Calculating the changes for mean participants, the authors found that a woman, without baseline CVD, diabetes or smoking, who is taking anti-hypertensive drugs, will move from an 8.6% 10 year global risk for CVD to a 3.9% risk. A man, with no CVD or smoking but whose diabetes and need for anti-hypertensive drugs resolves after surgery, will move from a 10 year global risk of 18.4% to 4.7%. PubMed: Bariatric Surgery and Cardiovascular outcomes: a systematic review

So, where are we? The gold standard of lifestyle change is tarnished. The drug story is muddy at best. Bariatric surgery is clearly producing the superior results. However, access to surgery is, and will remain, a problem. The challenge for the leaders in the field is to find ways to have surgery reach more people and not be a procedure for the 1 percent. Even with greater access to surgery, the obesity-diabetes epidemic will continue to be a major health crisis. It’s time to be humble in the face of this disease and realize a lot more research is going to be needed…and soon.


Obesity, diabetes to thwart cardiovascular improvements

May 3rd, 2012

Huffman and colleagues looked at the American Health Association’s Strategic Impact Goals target of a 20% relative improvement in overall cardiovascular health. They looked at 35,000 cardiovascular disease-free adults in the NHANES surveys from 1999 to 2008. They found that the prevalence of smoking, hypercholesterolemia and hypertension declined, whereas the prevalence of obesity and dysglycemia increased through 2008. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes could increase to affect 43% and 77% of US men and 42% and 53% of US women. Overall, population level cardiovascular health is projected to improve only 6% overall, far below the AHA 20% target. PubMed: Cardiovascular Health Behaviors Changes and Projections


American Heart Assn. Sees Tidal Wave of Cardiovascular Disease coming from Obesity Epidemic

December 16th, 2011

The American Heart Association has published an update on the burden of cardiovascular disease and stroke. They warn that the recent drop in death rates is likely to be reversed by the continuing increases in the rates of diabetes and obesity. Dr. Donald Lloyd-Jones told MedPageToday  that rising death rates in cardiovascular death in young adults is particularly troubling, “Because if they’re getting disease at this young of an age then they’re just the leading edge – the canaries in the coal mine, if you will – that suggests that we have a whole tidal wave of cardiovascular disease that is coming as a result of the obesity epidemic.” Medical News: Diabetes, Obesity Overshadow Lower CV Death Rate – in Cardiovascular, Prevention from MedPage Today 

Here are the facts:

The estimated prevalence of overweight and obesity in US adults (>20 years of age) is 149 300 000, which represents 67.3% of this group in 2008. Fully 33.7% of US adults are obese (body mass index >30 kg/m2). Men and women of all race/ethnic groups in the population are affected by the epidemic of overweight and obesity.

● Among children 2 to 19 years of age, 31.9% are overweight and obese (which represents 23 500 000 children), and 16.3% are obese (12 000 000 children). Mexican American boys and girls and African American girls are disproportionately affected. Over the past 3 decades, the prevalence of obesity in children 6 to 11 years of age has increased from <4% to more than 20%.

● Obesity (body mass index >30 kg/m2) is associated with marked excess mortality in the US population. Even more notable is the excess morbidity associated with overweight and obesity in terms of risk factor development and incidence of diabetes mellitus, CVD end points (including coronary heart disease, stroke, and heart failure), and numerous other health conditions, including asthma, cancer, degenerative joint disease, and many others.

● The prevalence of diabetes mellitus is increasing dramatically over time, in parallel with the increases in prevalence of overweight and obesity.

● On the basis of NHANES 2003–2006 data, the age adjusted prevalence of metabolic syndrome, a cluster of major cardiovascular risk factors related to overweight/obesity and insulin resistance, is 34% (35.1% among men and 32.6% among women).

● The proportion of youth (<18 years of age) who report engaging in no regular physical activity is high, and the proportion increases with age. In 2007, among adolescents in grades 9 through 12, 29.9% of girls and 17.0% of boys reported that they had not engaged in 60 minutes of moderate-to-vigorous physical activity, defined as any activity that increased heart rate or breathing rate, even once in the previous 7 days, despite recommendations that children engage in such activity >5 days per week.

● Thirty-six percent of adults reported engaging in no vigorous activity (activity that causes heavy sweating and a large increase in breathing or heart rate).

● Data from NHANES indicate that between 1971 and 2004, average total energy consumption among US adults increased by 22% in women (from 1542 to 1886 kcal/d) and by 10% in men (from 2450 to 2693 kcal/d;

● The increases in calories consumed during this time period are attributable primarily to greater average carbohydrate intake, in particular, of starches, refined grains, and sugars. Other specific changes related to increased caloric intake in the United States include larger portion sizes, greater food quantity and calories per meal, and increased consumption of sugar-sweetened beverages, snacks, commercially prepared (especially fast food) meals, and higher energy-density foods.

For the full report, see Heart Disease and Stroke Statistics—2011 Update1. About 1. About These Statistics2. American Heart Association’s 2020 Impact Goals3. Cardiovascular Diseases4. Subclinical Atherosclerosis5. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris6.

Primum Non Nocere*

November 28th, 2011

Many media outlets are reporting on the removal of a 200 lb. 8 year old from his family in Cleveland. Cleveland is, of course, the home of Toby Cosgrove, MD, head of the Cleveland Clinic, who proclaimed his desire to not hire workers who were obese. This came a year or so after the American Medical Association took the official position that persons who are obese are not entitled to compensation for being disabled for being unable to work. 

The intellectual justification for the forced removal of the child from his family is that provided by Dr. David Ludwig of Harvard Medical School.  State Intervention in Life-Threatening Childhood Obesity, July 13, 2011, Murtagh and Ludwig 306 (2): 206 — JAMA In the Commentary in July in the Dr. Ludwig had indicated that the forced removal by the state of children who were obese was justified. 

On what basis, you might ask? Well, there were several and they were all, in my opinion, intellectually bankrupt.

First, Dr. Ludwig and his co-author Lindsey Murtagh, J.D., assume “even mild parenting deficiencies such as having excessive junk food in the home or failing to model a physically active lifestyle, may contribute to a child’s weight problem.”

Excuse me? Before you go calling these “parental deficiencies,” how about defining: “excessive”, “junk food” or “failing to model a physically active lifestyle? Well, forget about it. They don’t define their terms.

What do they mean by “may contribute” to a child’s weight problem? If you are arguing that these “mild parental deficiencies” cause life-threatening conditions, is “may” good enough? What is the degree of evidence? If you are arguing that these conditions merit breaking up a family should not the evidence be like, beyond a reasonable doubt or a preponderance of the evidence? Is “may” good enough?

Second, they posit that severe obesity (a BMI at or beyond the 99th percentile) represents a fundamentally different situation than most overweight and obese children who have “the opportunity to ameliorate these risks through behavior change and weight loss as adults.” So, they say that severe obesity is fundamentally different “suggesting profoundly dysfunctional eating and activity habits”. Obesity of this magnitude can cause immediate and potentially irreversible consequences, most notably type 2 diabetes”.

Excuse me? Where is it written that persons with severe obesity as a child have a much smaller likelihood of reversing it as an adult than those with a lower level of obesity?

And what makes the BMI, which we know is a limited measure of body adiposity, at the 99th percentile different from the 97th percentile or the 95th percentile or the 92nd  percentile for that matter?

They argue that  severe obesity ‘suggests’ profoundly dysfuncitional eating and physical activity habits? ‘Suggests?’ They aren’t sure? If they are proposing breaking up a family maybe something more than ‘suggests’ is warranted. More importantly, could it not be that we are confusing cause and effect.  If there is anything to the increases in height and weight over the past 350 years, if there is anything to the contribution of genetic inheritance to obesity, if there is anything to the contribution of epigenetic factors to obesity, then, we must at least allow the suggestion that some children are born programmed to be overweight or obese. Upon achieving that status, one would assume they would overeat and underexercise compared to their normal weight peers. Would these be acquired ‘habits’ or the adaptions to their body habitus?

When they say that obesity of this magnitude can cause immediate and potentially irreversible consequences, most notably type 2 diabetes, what do they mean? Only a subset will develop type 2 diabetes immediately and for many, it will be manageable by lifestyle, drugs or surgery. Others, at a BMI lower than the 99th percentile and some who are merely overweight or normal weight will develop diabetes as well.

Third, (here’s the rub) the authors point with alarm that these patients may have to have bariatric surgery, whose long-term safety and effectiveness is not established. Therefore, they propose an alternative “therapeutic approach” i.e., placement of the severely obese child under state protective custody. The authors state, “Indeed, it may be unethical to subject such children to an invasive and irreversible procedure without first considering foster care.”

Doh? Did I get this right? Because at some point in the future, a child has continued to suffer with obesity and decides to have bariatric surgery, Ludwig and Murtagh propose the state comes in when the child is a juvenile and break up the only family the child has ever known?

Friends, I have worked for years with the professional jealousy of surgeons and internists and non-physician health care professionals. For the most part, they keep these often bitter inter-professional competitions to themselves. But this approach of Ludwig and Murtagh is nothing more than saying that breaking up a family, taking an obese child away from their mother and father and siblings, making them a ward of the state, having them raised by strangers who are paid for their care is better than even the potential that someday that person may want/be eligible for/can pay for bariatric surgery. 

The bias is demonstrated by the additional point raised by the authors that, “Although removal of the child from the home can cause families great emotional pain, this option lacks the physical risks of bariatric surgery. Moreover, family reunification can occur when conditions warrant, whereas the most common bariatric procedure (Roux-en-Y anastomosis [gastric bypass]) is generally irreversible.” Well, this is factually wrong. Roux-en-Y is not the most common bariatric procedure. The reversible laproscopic gastric banding is. Metabolic/bariatric surgery Worldwide 2008. [Obes Surg. 2009] – PubMed – NCBI  And  emotional pain may play a  particularly important role on the development of obesity. See this recent post.

And what does family reunion “when conditions warrant” mean? There are several options here which are starkly different and completely unaddressed by the authors. One option is that the obese child has returned to normal weight. The second option is that the obese child is still obese or has lost some weight but has improved eating or physical activity behaviors. The third option is that one parent or both have improved their ‘deficiencies’ by (a) removing only ‘excessive’ junk food in the home and/or (b) modeling a physically active lifestyle, independent of any change in the child. (Did I mention that the NIH guidelines for pediatricians on weight management did not find much support for physical activity?)

The fourth option is that that the foster care parents are both removing excessive junk food and modeling a physically active lifestyle and the child is continuing to gain weight. In some cases, there may be no “family reunification” but a succession of foster homes, all equally unable to affect the child’s excess adiposity. 

At the very end of their Commentary, Ludwig and Murtagh do a bit of a CYA, stating, “Nevertheless, state intervention would clearly not be desirable or practical, and probably not be legally justifiable, for most of the approximately 2 million children in the United States with a BMI at or beyond the 99th percentile. Moreover, the quality of foster care varies greatly; removal from the home does not guarantee improved physical health, and substantial psychosocial morbidity may ensure. Thus, the decision to pursue this option must be guided by carefully defined criteria such as those proposed by Varness et al with less intrusive methods used whenever possible.”

Now, dear reader, when one comes upon a statement like this, one assumes that Varness, et al, is in at least broad agreement with Ludwig and Murtagh. So it came as some surprise to actually read the cited Varness articles. See Childhood obesity and medical neglect. [Pediatrics. 2009] – PubMed – NCBI 

What Varness says is that, for a child to be removed from their home, all 3 of the following criteria have to be met: (1) a high likelihood that serious imminent harm will occur; (2) a reasonable likelihood that coercive state intervention will result in effective treatment and (3) the absence of alternative options for addressing the problem.

Regarding #1, a high likelihood that serious imminent harm will occur, Varness states, “The mere presence of childhood obesity does not predict serious imminent harm…Although childhood obesity is a risk factor for the development of multiple diseases as an adult, increased risk for adult diseases does not constitute serious imminent harm.” At the other end of the spectrum are current risks, such as severe obstructive sleep apena with cardiorespiratory compromise, uncontrolled type 2 diabetes and advanced fatty liver disease with chirrhosis. In some cases, like advanced hepatic fibrosis, the harm cannot be reversed in adulthood. Varness et al state, contrary to Ludwig and Murtagh, “There is no clear threshold level of childhood obesity (overweight, obese, or severely obese) that automatically predicts serious imminent harm….Although it is true that childhood obesity can lead to adult obesity, childhood obesity itself does not seem to lead to irreversible changes that are significant enough to mandate coercive state intervention.”

Regarding #2, a reasonable likelihood that coercive state intervention will result in effective treatment, Varness states, “In other words, is it truly reasonable to demand that families be able to achieve effective weight loss for their children? In addition, if it has been impossible for a family to reduce weight, what evidence is there to suggest that removal from the home would be more successful?” 

Regarding #3, the absence of alternative options for addressing the problem, Varness clearly does not share Ludwig and Murtagh’s antipathy for bariatric surgery. He states, “In summary, medications and surgery hold some promise but still have a questionable risk/benefit ratio, in both the short term and the long term. Although these may seem to be attractive options for some motivated adolescents with severe obesity, they are not options that are likely to be mandated for a child over the family’s objections. In contrast to the Ludwig-Murtagh paradigm of “mild parenting deficiencies,” Varness observes, “ In most cases of obesity, families make a good-faith effort to address the problem when they are made aware of the condition and the potential adverse health consequences. The development of a serious comorbidity can serve as a “wake-up call” for families, prompting full cooperation with intensified medical services.”

In sum, Varness makes the case that state intervention for obese children with no comorbidity is not justified; for those with a serious imminent harm, e.g. obstructive sleep apnea with cardiorespiratory compromise, intervention is probably justified. In between, only those risks known to be irreversible as an adult, such as hepatic fibrosis resulting from nonalcoholic fatty liver disease as opposed to cardiovascular disease, seems to be justified.

Finally, contrary to the misinformation about bariatric surgery, Varness notes that, “If a medical or surgical intervention that has a very high probability of decreasing weight with minimal adverse events is developed, then the availability of this effective treatment might result in a stronger intervention on behalf of children. For instance, gastric banding is a reversible procedure that involves the laparoscopic placement of an adjustable band around the proximal stomach. This procedure is not approved by the Food and Drug Administration for adolescents, and long-term data on its efficacy and complications are lacking. However, this procedure may hold some promise for extremely obese children, particularly as it is reversible.” In other words, coercive state action may be justified for bariatric surgery, rather than as an alternative to bariatric surgery, as desired by Ludwig and Murtagh. Not to belabor the point, but it seems Varness contradicts every major point Ludwig and Murtagh make. Curious, no?

My problem with the Ludwig-Murtagh commentary is not just on its intellectually bankruptcy and the harm it is bringing on persons who have enough pain it their lives. It is the question of what is Organized Medicine doing? So the position of Organized Medicine is this: Persons with obesity should be denied jobs (and, presumably, employer-provided health care), denied disability compensation when they cannot work, empathetic treatment by their physician and now the support of their own families in favor of unknown, paid-to-be-parents in foster care? Shouldn’t medicine be looking for better treatments? Maybe diagnosing their own patients? Maybe making appropriate referrals? Why don’t Dr. Ludwig and Attorney Murtagh call on pediatricians to develop better treatment protocols for children and adolescents with obesity? Why don’t they call on the American Academy of Pediatrics to lobby for dedicated funding for research on new treatments? Why don’ they criticize their fellow pediatricians who neglect to advise their patients on weight loss, in my opinion, unethically so. Pediatricians, in particular, have spent decades telling parents their children will ‘grow out of’ their weight problems. Now that obesity has become epidemic, they have done next to nothing to actually treat the disease, instead pointing to food companies’ marketing, television viewing, computers, vending machines, and parents as the culprits. Is it too much to ask them to develop treatments for their patients and quit blaming everyone else?

This blaming is only driving parents away from consulting with primary care providers, as discussed in Dr. Arya Sharma’s blog today.

If medicine, and especially, pediatrics, cannot help, at least stop making matters worse. 

See County places obese Cleveland Heights child in foster care |

Associated Press, MSNBC News: U.S. News – Ohio puts 200-pound third-grader in foster care

ABC News: Health » Obese Third Grader Taken From Mom, Placed in Foster Care Comments Feed

Background: Should parents lose custody of super obese kids? – Washington Times 

* Latin for “First, Do No Harm”

What’s Up with the FDA? Part 1

May 6th, 2011

Faithful readers will recall that I spent two days last July at the FDA Endocrinologic and Metabolic Advisory Committee reviewing rosiglitizone (Trade name Avandia). Avandia, for type 2 diabetes has been interesting to follow not just because so many persons with obesity develop type 2 diabetes but because, due to its review coming amid the same Advisory Committee’s review of four obesity drugs, provided additional insights, especially into how the FDA evaluated safety concerns.

This became all the more interesting when the FDA decided to keep Avandia on the market, albeit with endhanced warning, but had Abbott Laboratories take sibutramine (trade name Meridia) off the market.  The point was made that Avandia had a number of fatal events, in its intended population while Meridia had no fatal events in a population which was specifically excluded on its label. Yet Meridia was spiked and Avandia was not.

Now comes a meta-analysis of Avandia’s class of drugs, called thiazolidinediones, which also includes pioglitazone, (Trade name Actos). The study, covering 16 studies with 810,000 patients found 170 excess myocardial infactions, 649 excess cases of heart failure and 431 excess deaths for every 100,000 patients who receive Avandia rather than Actos. Probably, this will not be enough for the FDA to take any stronger action against Avandia. See Comparative cardiovascular effects of thiazolidine… [BMJ. 2011] – PubMed result

A DASH of Salt?

May 6th, 2011

So salt is back in the news. On May 3, 2011 Gina Kolata (one of the best reporters on nutrition issues around) reported on a new study which found that a low salt diet increased the risk of death from heart attacks and strokes and did not prevent high blood pressure. Study Finds Low-Salt Diet Ineffective but Draws Criticism From C.D.C. – See the abstract  at Fatal and nonfatal outcomes, incidence of hyperten… [JAMA. 2011] – PubMed result. But the real story she reported was the pushback from the Centers for Disease Control and Prevention which seemed to be going out of its way to attack the study. The discussion pointed out the differences in the scientific literature on low salt diets, noting that lowering salt consumption can increase insulin resistance which can increase the risk of heart disease, contrary to prevailing wisdom.  Dr. Lawrence Alderman is quoted with the insight every weight watcher knows, “Diet is a complicated business.” But beyond that, the article shows the complexity ofblood pressure and hypertension, two conditions often associated with obesity but often unpredictable in their response to changes in body weight.

The Obesity Society Meeting-Day Two

October 26th, 2009

Today’s sessions of the Obesity Society’s annual scientific meeting covered a lot of ground.  I think the most interesting  was the session on the relationship of cancer and obesity organized by Ruth Ballard-Barash of the National Cancer Institute and Ted Adams of the University of Utah School of Medicine. Christine Friedenreich, Ph.D. of the Alberta Health Services presented a comprehensive overview of the association between specific cancers and obesity, reviewing the published literature for each cancer. At the end, she proposed that obesity was responsible for about 20% of all cancers. If (in an ideal world) obesity levels could be resolved to normal BMIs, she speculated 1.6 million deaths due to cancer could be saved, 2.2 million new cancer cases could be avoided and we could avoid having 5 million persons living with cancer.

Other key presentations addressed the powerful influence of sleep and circadian rhythms, or the lack thereof, on rising rates of obesity. This led one presenter to suggest that we should have our biggest meals at breakfast and gradually reduce caloric input throughout the day to a light salad at dinner. Rena Wing reported on the 4 year results of the Look Ahead Trial which provided persuasive information for intensive lifestyle counseling over less intensive interventions in reductions in body fat and related metabolic indicators.

Sometimes these meetings morph into abstract, perhaps irrelevant, discussions of minutia   among researchers.  At other times, you feel you are witnessing an emerging new insight into obesity and its effects. So it was today in a session, Is There Good and Bad Body Fat? chaired by Richard Bergman, editor of Obesity, and including prominent researchers, Tamara Harris, Michael Jensen (who readers may remember from our conference at the 2008 Republican National Convention) and Sam Klein. Their task was to unravel which fat was bad and which was good. Their presentations covered detailed, precise research into these tangled issues.  Why are there some obese individuals who were, nevertheless, metabolically normal? Why did bariatric surgery resolve diabetes in some cases but not others?  Why does weight loss resolve some metabolic disorders but not others? For many in the audience, these are the cutting edge questions – today – to understand the metabolic sequela of weight gain, insulin resistance, diabetes and cardiovascular disease. The presenters provided exciting new data interspersed with a camaraderie and jocularity which is the realm of highly accomplished and competitive scientists who admire each other’s works but are not going to give them an inch. Bottom line: adipose cell build up in the liver may explain many of the inconsistencies in present views of the obesity-insulin resistance-metabolic disorders axis. But, build up of adipose cell in the liver is hard to measure given today’s technology and bio-statistical resources. On the other hand, there may well be another factor, not yet identified (kind of like dark matter in astrophysics), which modulates the effects of obesity, insulin resistance and metabolic disorders. The large, enthusiastic audience no doubt left with many possible research proposals in mind to unravel this conundrum. Stay tuned, as they say, “we wait with bated breath,” for the next insight.

Time for Obesity in Health Care Reform

September 27th, 2009

January 30, 2009 :: By Morgan Downey

These are exciting times for health care reformers. We seem to have a President who is truly committed to reform of the health care system with the political strength to get his program enacted, at least a good part of it. What is the President’s program and how does or can, obesity be part of it?

First, some parts have already been enacted in the American Recovery and Reinvestment Act (ARRA), aka the Stimulus Bill. Millions of federal dollars are starting to flow into (a) expanded Health Care Information Technology, (b) comparative-effectiveness research and (c) expanded research at the National Institutes of Health. In addition, President Obama and several of his key aides, such as Melody Barnes, Director of Domestic Policy Council, and Peter Orszag, director of Office of Management and Budget have both addressed obesity and its important role in reducing health care costs and increasing the nation’s health.

Second, a major component to be worked on this summer is providing health insurance to millions of Americans without health insurance.

How might these plans affect obesity?

Healthcare Information Technology (HIT) may provide some interesting opportunities. In a few places, extensive clinical databases are already in use which track patients receiving bariatric surgery. The Surgical Review Corporation, for one, has 100,000 surgical patients which are being tracked for long-term outcomes. The Geisinger Medical Center in central Pennsylvania also has extensive database on patients in surgical and medical treatment. Such clinical registries can provide a vast improvement in understanding obesity and its co-morbidities as well as tracking long-term improvements. Doing this in real time with real-world patients can add tremendous information to clinical trials, which, by their nature, have more restrictive populations and end-points. Last year, the National Committee on Quality Assurance (NCQA) expanded the widely used HEDIS system which measures quality in managed care plans to capture Body Mass Index (BMI) for adults and children. The Administration’s emphasis on electronic medical records (EMR) in primary care practice, by requiring capture of BMIs, along with other clinical indicators, such as blood pressure, cholesterol levels and lipids, can provide a tremendous database for researchers and has the potential to greatly improve patient care. But there is a third level as well. Private entities, such as Google and Microsoft, are developing Personal Health Records (PHR) for individuals to track their own information, which might include nutritional and exercise patterns. One can almost envision a system whereby food and exercise diaries, clinical indicators, pharmaceutical and surgical information is available for patients, health care professionals and researchers.

Of course, such systems take a lot of effort. Common terminology must be agreed to. Data has to be able to be verified. Systems have to interface and patient privacy has to be protected. Who owns this information is a critical issue.

Comparative effectiveness research has already received a great deal of funding under ARRA. The Institute of Medicine has a panel recommending research priorities and, given the discussion at a public meeting on March 20, 2009, there is good reason to anticipate that obesity will be one of the priorities. But the question should not be just what is the best way to lose weight. The research should look at weight loss by various interventions against standard treatments for a number of the co-morbid conditions associated with obesity. And, while there is good data on the efficacy of weight loss for resolution of type 2 diabetes and cardiovascular disease, less is know about its efficacy in mobility problems, such as knee and hip replacements, asthma or breast cancer.

Finally, the Obama Administration has an enormous opportunity in the coverage of the uninsured to make a real change for persons with obesity. First, the Administration should oppose using overweight or obesity as a pre-existing exclusion. While we do not know what percent of the uninsured population is overweight or obese, it is unlikely that the rate is any lower than the national averages. To exclude 30-60% of the uninsured population because of their weight would be poor policy indeed. Next, the Administration should provide a full range of interventions from counseling on nutrition and physical activity to pharmaceutical and surgical interventions. Not only would this directly address the source of many of the uninsured population’s health care problems, it could break the logjam of resistance to coverage of obesity prevention and treatment. While these two steps will be costly, we have seen the rising rates of health care costs and obesity go hand-in-hand. Economists today see obesity as a major contributor to chronic illness and its costs. Finally, coverage should be tied into electronic records which can track long term outcomes.

In the April 15, 2009 issue of the Journal of the American Medical Association, Johathan Q. Purnell and David R. Flum estimate that gastric bypass surgery could save 14, 310 diabetes-related deaths over five years. The evidence on the power of weight loss to prevent and improve chronic disease is there, if not yet perfect. The Administration has an opportunity to make a major leap forward in addressing obesity. It should not miss this chance.