Last Resorts: When Altering
Your Environment Isn’t Enough
Jared is a fifteen-year-old who has been obese his whole life. He is very self-aware and knows the repercussions, both medically and socially. We test him for genetic mutations, and nothing turns up. His oral glucose tolerance test exhibits massive insulin release, but no insulin resistance. We place him on octreotide, which stabilizes his weight for a total of ten months; but then his weight continues to increase. Other medicines are of no use. In his senior year of high school, he undergoes a laparoscopic adjustable gastric band (LAGB) procedure. Over the next year, his appetite abates, his weight reduces from 366 to 222 pounds. His mother reports, “We just went out to dinner, and I overheard someone at the next table say, ‘What a good-looking family,’ and I thanked God and started to cry.”
Obesity is not a behavior. It is not even a disease (as that would assume a common pathophysiology). Indeed, obesity is a phenotype (a composite trait) of many different pathologies. Remember, there are three different organ systems that could be dysfunctional—the brain (see chapters 4–6); the fat (see chapters 7–9); or the hormones that affect the brain or the fat (see chapter 18). Obesity was, is, and will be, forever. But it need not exist at this frequency. The problems of hunger (hypothalamic dysfunction), reward (nucleus accumbens dysfunction), or stress (amygdala dysfunction) can overwhelm just about anyone. And if you create extra fat cells along the way (e.g., steroid use for cancer therapy, or extra insulin before birth due to the mother’s prenatal diet or her gestational diabetes), those cells aren’t going to give up their energy without a fight. Alterations in the food and hormonal environments will work for 50–60 percent of the population, but there will still be people who can’t overcome those biochemical forces. To the best of our ability, we need to determine the individual basis for the obesity to best treat its underlying causes. Otherwise, we are fighting the wrong problem. The key to successful therapy in these patients is accurate diagnosis. Unfortunately, our diagnostic armamentarium is not yet fully developed, so matching treatment to diagnosis remains uncertain.
There is not, and never will be, a magic bullet for obesity or metabolic syndrome, especially if you consume four sodas a day. This chapter is written with the working assumption that a formal six-to-twelve-month period of food and hormonal environmental alteration—including psychodynamic, cognitive, and/or family therapy where necessary—has been attempted, and has not been effective. What then? It’s time to move to the bigger guns.
Drilling Down Through the Fat:
Laboratory Tests and Your Health
Chapter 8 reviewed methods for ascertaining your level of visceral fat. Every other method to assess your metabolic risk is relatively expensive and requires blood drawing, specialized equipment, and/or professional data analysis. These tests and their analysis should be left to your physician. But you should know what they mean, as they are important for gauging your health.
The Lipid Conundrum
Virtually everyone in America now gets a fasting lipid profile (aka cholesterol test) to assess their risk for heart disease. But there’s a lot more to the lipid profile than meets the eye (see chapter 10), and this field is continually evolving. In the 1970s, scientists determined that LDL (low-density lipoproteins) were the bad type of cholesterol, whereas HDL (high-density lipoproteins) were beneficial. In the early 2000s, we learned that the triglyceride (TG) level also correlated with heart disease risk, especially in light of the obesity pandemic. The TG-to-HDL ratio is a surrogate marker of oxidized LDL (the LDL that lines arteries), insulin resistance, and metabolic syndrome. When you get a fasting lipid profile, your doctor needs to look at all the lipid fractions, as they cannot be viewed in isolation.
Alanine Aminotranferase (ALT)
Diagnosing metabolic syndrome is all about assessing the fat in the liver.1 While not specific for liver fat accumulation, the liver enzyme ALT is easy to assess and is a good predictor of future diabetes.2 Most doctors get nervous with an ALT above 40, but recent data argue that even an ALT of 25 predicts liver fat.
Fasting Insulin, Glucose, and Hemoglobin A1c
Every doctor gets a fasting glucose on his adult patients, looking for type 2 diabetes. This parameter is the very last one to change; by the time it has gone south, metabolic syndrome is in full force, and there are no options for prevention anymore. The body will do everything it can to maintain the serum glucose in the normal range, including increasing the insulin. (That’s insulin resistance!) So the way to interpret a fasting glucose is by getting a simultaneous fasting insulin level, which tells you how hard the pancreas is working. However, a fasting insulin will tell you only about insulin resistance. It won’t tell you about excessive pancreatic insulin secretion.
In our clinic, we assume insulin resistance when we see a patient for the first time, because it is so common. If the patient responds to an environmental intervention (see chapter 18), there is no further need for testing. If she doesn’t, we use an oral glucose tolerance test to see if she releases too much insulin3 (see chapter 4), and then determine the best course of therapy to lower insulin release.
Doctors have started to screen patients with hemoglobin A1c (HbA1c), the blood test that assesses glucose control over the preceding three months and is used to monitor diabetic patients. By everyone’s estimation, under 5.5 percent is normal, over 6.5 percent is diabetes, while 6.0–6.5 percent requires a glucose tolerance test to determine if diabetes is present.4
Inflammation Markers
Metabolic syndrome is also about inflammation and cell damage. All these tests (such as high-sensitivity C-reactive protein) are very expensive, none is paid for by standard commercial insurance, and none has been shown to predict with precision the timing of a heart attack or stroke. Thus, while they show promise, all tests remain subjects of research and have not yet been adopted clinically.
Seeing Is Believing: Imaging Studies
When it comes to obesity, a picture truly is worth a thousand words. Is there any way to tell what your belly and your liver are up to? Yes, but they are all expensive, research-based, and not likely to be readily available soon. Liver ultrasounds have a high specificity for detecting fatty liver (meaning when it’s there, you can see it), but the sensitivity is relatively low (meaning that you can think it’s there, but it’s not). Another test is called dual emission X-ray absorpiometry (DEXA). While fat tissue can very easily and nicely be quantified, it’s impossible to tell what type it is (subcutaneous, visceral, or liver), so such a measure is of limited use. Two more methods are CT and MRI of the abdomen, which can differentiate the different storehouses of fat. Both MRI and CT cost more than $1,000 a pop and are not covered by insurance, which puts them out of the reach of most patients.
Once you know whether you’re fat or sick or both, and once your doctor has ruled out specific genetic or biochemical abnormalities, you and your doctor can make a conscious decision as to the most appropriate mode of therapy, and how best to monitor your progress.
The Obesity Drug Pipeline—a Trickle, Not a Gusher
Sadly, drug therapy for obesity has hit the skids. It seems incredible that in the face of the relative lack of efficacy of lifestyle interventions, the ever-expanding knowledge of the physiology of energy balance, and a veritable gold mine for successful candidates, most pharmaceutical companies have closed their obesity research programs.
A new anticancer therapy that can show an increase in survival for four extra months can get FDA approval despite severe side effects, yet the bar has been set so high on obesity drugs that any that demonstrate even the slightest toxicity are doomed to failure. The FDA is tasked to do a cost-benefit analysis on every new drug. Are the potential side effects worth the risk? FDA commissioner Margaret Hamburg believes that obesity is about “making healthy choices,” therefore, why would you need drugs? There are numerous medications for the diseases within metabolic syndrome, but virtually none targeting patients before these illnesses develop. The FDA has recently withdrawn three medications (ephedrine, sibutramine, and phenylpropanolamine) due to concerns over potential toxicity. Only orlistat (Xenical or its over-the-counter version, Alli) is still with us. It barely works, has adverse effects galore, and is in a fight for its life over possible liver toxicity. The FDA recently voted down three combination drugs (although one of these, phentermine-topiramate, or Qsymia, made it through on the second try in 2012). And they just gave the go-ahead to lorcaserin in July 2012.
What’s Left of Pharmacotherapy—Last Drug Standing?
This leaves very few medications to talk about. Furthermore, obesity drugs don’t have a great track record. Energy balance is so crucial to survival that we want to hold on to our fat at any cost. Every obesity drug works for about four months, and then that negative plateau kicks in (see chapter 4). Every drug has side effects, some of them serious. Each drug is tested in combination with a low-calorie diet, therefore every drug must currently be considered an adjunct to standard environmental modification, which is not the way people use them in real life. You have to do the right thing anyway. Obesity drugs work on different aspects of energy balance. Currently, the approaches are: reducing calories eaten (phentermine), reducing energy absorbed (orlistat), increasing energy expended (nothing left here), and improving either insulin resistance (metformin) or suppression of insulin release (a low-carb diet).
While many new drugs are currently under study, and many of them are attempts at targeted therapy, proof of safety and efficacy are hard to come by. One reason is that obesity is not one disease but many, so each drug will work only in a percentage of people. Another reason is that the mechanisms to maintain your weight are redundant and strong, so treating one pathway is often not enough. Many experts have abandoned the idea of a big blockbuster agent that will “cure” obesity,5 and have instead started advocating combination drugs that target different parts of the energy balance pathway. But that means drug companies would have to work together, which is like expecting Apple to love Microsoft. And that means no home runs, only the occasional single. Just as in baseball, don’t expect the pharmaceutical houses to invest the bankroll for a singles hitter.
Bariatric Surgery—Not a “Magic Scalpel”
In adults with comorbidities and in adolescents with extreme and life-threatening obesity, surgical therapy may be necessary. Bariatric surgery can not only promote weight loss, but also reverse type 2 diabetes in up to 50 percent of patients, and might help you live longer.6 Yet it is virtually impossible to perform randomized controlled trials of bariatric surgery due to ethical concerns; you can’t do a sham surgery on people. And no studies take the causes or mechanisms of the obesity into account. So the efficacy of targeting any approach to any given patient will continue to be suspect.
Bariatric surgery is most effective in preventing the development of the various comorbidities associated with obesity before they take hold, such as diabetes and obstructive sleep apnea. By the time you have developed these disorders, surgery may improve them but will likely not reverse their presence. However, many insurance companies will not approve this procedure until you qualify with one of these life-threatening diseases. Also, if you wait until you are severely obese (more than 450 pounds), you are unable to have the surgery anyway, as you cannot fit in an MRI scanner, which is needed to observe your post-op progress. A catch-22.
In adolescents, performing surgery early in the game (only among the severely obese) will likely add years to their lives. They may even be spared the ravages of metabolic syndrome. However, the insurance company will opt to wait as long as possible, when the patient is no longer covered under his parents’ insurance. Therefore, guidance is needed to determine the ideal circumstances when the balance of risk versus benefit favors health improvement and reversion of complications, yet with the lowest risk of morbidity and mortality.
Surgical outcomes in adults vary between surgeons and institutions. The only method to validate and refine the use of these procedures comes from following patients carefully and long term,7 which is of no use to the patients undergoing surgery today. It is absolutely essential that bariatric surgery be performed in regionalized academic centers with programs equipped to handle the data acquisition, long-term follow-up, and multidisciplinary nature of these difficult patients.8 However, by restricting the number of sites, you limit the number of surgeries that can be performed, and access to them.
One of the biggest public misconceptions is that bariatric surgery consistently works in the long term. That’s the party line toed by the media, the bariatric centers, celebrities such as Al Roker, Sharon Osbourne, and Star Jones, and the “cut-and-run” surgeons. But for how long? Virtually everyone loses weight for the first twelve months.9 But the real story is told after the one-year breakpoint. Up to 33 percent of patients gain much if not all their weight back.10 The stomach can easily restretch to accommodate excessive food intake. In many procedures, the stomach is reduced from the size of a baseball glove to that of a golf ball. The sensation of hunger is reduced, and the feeling of fullness is achieved after smaller portions are consumed. Great. But, as mentioned, many of the obese don’t only eat when they are hungry. The underlying causes of the obesity—the “behaviors” of reward and stress (see chapters 5 and 6)—are not even remotely alleviated by these procedures, and not addressed by most patients or doctors. And the procedure doesn’t prevent you from drinking your calories, which will bring you back to your initial weight even faster. These patients need long-term psychotherapy in addition to surgery. The point is that bariatric surgery is an adjunct to dietary and environmental change, not a “magic scalpel.”
You Can Pay Me Now, or You Can Pay Me Later
Very few people can afford to have these procedures, as they can cost anywhere from $15,000 to $40,000 just for the surgery, let alone the pre-op evaluation, any complications, and the long-term follow-up. If Al Roker and Sharon Osbourne can get it, why can’t you? Because your insurance company doesn’t want to pay for it. Yet several cost-benefit analyses have been done that say that bariatric surgery increases both longevity and quality of life.11 It actually reduces health-related costs, especially those associated with treating type 2 diabetes. And the strain on the medical system—by 2030 we will be taking care of a hundred million diabetics in the United States alone—might just ease slightly.
Bariatric Procedures
Bariatric procedures (colloquially referred to as “stomach stapling”) can be divided into malabsorptive (food goes out in the stool), restrictive (food can’t get into the stomach), and a combination of the two. Purely malabsorptive procedures (such as the duodenal switch and the jejuno-ileal bypass) have extremely high morbidity and mortality, and cannot be recommended. The Roux-en-Y gastric bypass (RYGB) is a combination procedure, which not only leads to extraordinary weight loss but can reverse type 2 diabetes as well.12 The restrictive procedures reduce stomach volume to decrease the volume of food ingested. They include the Bioenteric Intragastric Balloon (BIB),13 laparoscopic adjustable gastric band (LAGB),14 and sleeve gastrectomy (SG).15 Unfortunately, the general safety of these procedures correlates inversely with the degree of weight loss—the safer the procedure, the less weight lost—so there is no “favored” type.
Unlike with adults, stricter and more conservative criteria must be applied to adolescents, since only 85 percent of obese adolescents will become obese adults; the slightly improved rate of lifestyle and pharmacotherapeutic efficacy versus that of adults; a longer time interval before comorbidities become life-threatening; and children’s inability to give legal consent. For all these reasons, an expert panel with representation from the American Pediatric Surgical Association and the American Academy of Pediatrics has suggested that bariatric surgery for adolescents should be done only in institutions committed to long-term management of these patients,16 and is justified in situations when obesity-related comorbid conditions (such as obstructive sleep apnea) threaten the child’s health. While I must accede to this view, my personal feeling is that usually the horse is out of the barn by then. Waiting until a child is fully grown can mean many more pounds and much more comorbidity, which could be avoided by confronting the problem earlier. It is easier to stabilize weight gain than it is to induce weight loss. But the degree to which this surgery should be used as a solution will have to wait until we have further data.
Last Resorts versus First Passes
The fact that any of the medications or procedures in this chapter exist, let alone are common, speaks to the breakdown of our energy balance pathway and the alterations in our environment that have led to that breakdown. These last resorts are clearly necessary for the 5 percent of the population who have a biochemical abnormality, and who would have been obese ten, one hundred, or even a thousand years ago. But for the other 95 percent of people, of whom 60 percent are overweight or obese, and for the 40 percent of normal-weight people who have metabolic syndrome, do we have to jump to last resorts first? Do we have the money for last resorts for every obese patient in America? Clearly, something needs to happen on the first pass. And that’s where public health comes in. Part 6 will make the argument that public health is our best and only chance worldwide to turn this juggernaut around.