Are Obesity Genetics Written In Stone?

In my practice, I often talk about the genetic predisposition to obesity.

Modern science has now identified over 100 genes that are associated with obesity, with each of these genes contributing a pound or two to the overall weight struggle.  So if a person has a high number of these 'bad' genes, they will have a bigger struggle with obesity, and a higher 'set point' of body weight, than someone who has only a few of these genes.   This can seem like a huge bummer - you can't change your genes (side bar: well actually you can but not in a good way - that's a story for another day) - so does this mean that the efforts to lose weight are hopeless?

The answer is, no.  Even for people who have more of the obesity-engendering genes, it is possible to lose weight, though a realistic weight goal will likely be higher than someone who has less obesity engendering genes.  In addition, a new study sheds light on gene-environment interactions in obesity, teaching us that certain behaviours can modify the effect of our genes on our body weight.

The study, published in PLOS Genetics, looked at gene-environment interactions for body mass index, using a large database of over 350,000 Caucasian people from the UK Biobank.  They found 15 lifestyle factors that influence our genes' effects on body weight, including:

• alcohol intake frequency
• usual walking pace
• socioeconomic status
• number of days per week of physical activity lasting at least 10 minutes
• time spent watching TV
• frequency of climbing stairs
• smoking 

So, the good news here is that we CAN influence our genes' effect on body weight to some extent with the lifestyles we lead. While some of the ability to use these factors may be affected by e.g. physical limitations, I think it's encouraging to know that the effect of our genetics are not set in stone.

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www.drsue.ca © 2017

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How Successful is Gastric Bypass Surgery 12 Years Later?

We know that gastric bypass surgery is a powerful tool in the management of obesity and metabolic syndrome.  However, there is not a lot of data available following patients out over the very long term.  A recent study is the first prospective study looking only at Roux-en-Y gastric bypass surgery, to give us data out as far as 12 years.

The study, published by Adams and colleagues in the New England Journal of Medicine, enrolled 418 patients in Utah, USA who underwent gastric bypass surgery, and compared them over the long term to 417 patients who wanted surgery but did not have surgery (primarily because of lack of financial insurance coverage), and a third group of 321 patients with obesity who were not interested in surgery. They had an excellent rate of follow up of over 90% of patients at 12 years.

Here are some of the key findings: (skip to take home messages below for the short version)

1.  Weight loss:

• Two years after gastric bypass surgery, the mean weight loss was 45 kg. 
• At 6 years postop, the mean weight loss was 36.3kg (so there was about 20% weight regain, which is very consistent across studies).
• At 12 years postop, the mean weight loss was 35kg – so weight was overall stable from 6 years to 12 years after surgery.

 [At 12 years, people who wanted surgery but didn’t have it had lost 2.9 kg (probably because they were part of this study), and people with obesity who did not want surgery had lost 0 kg (also notable for no weight gain over the long term).]

2.  Type 2 diabetes:

Among patients in the surgery group who had type 2 diabetes before surgery:

• At 2 years postop, 75% of diabetes had gone into remission.
• At 6 years postop, 62% of diabetes cases were in remission
• At 12 years postop, 51% of diabetes cases were in remission.
• The likelihood of diabetes being in diabetes remission at 12 years was 8.9 times higher for those who had had surgery compared to those who wanted but did not get surgery, and 14.8 times higher than those who did not want surgery in the first place.
• At 12 years, the likelihood of being in diabetes remission was highest in people who had diet controlled diabetes before surgery (remission rate 73%), less for people who needed pills to treat their diabetes before surgery (remission rate 56%), and lowest for people who required insulin to treat their diabetes before surgery (remission rate 16%). 
• At 12 years, there was a 91-92% lower risk of having new type 2 diabetes develop in patients who had had bariatric surgery, compared to the non surgery groups.

3.  Mortality rates:

At 12 years, mortality in people who had gastric bypass surgery was lower than those who wanted surgery but didn’t get it, but there no different between those who had gastric bypass surgery than those who didn’t want surgery in the first place, likely because the group not wanting surgery was healthier at baseline. There were 5 suicides in the group that had bariatric surgery, compared to 2 suicides in the non surgical group.  (see here and here and here for discussion of suicide risk after bariatric surgery ) 

Take home messages from this study:

• On average, weight loss is stable over the long term after gastric bypass surgery – though the results can be different for different people, and certainly lifelong dedication to permanent lifestyle changes are essential for continued success.

• Gastric bypass surgery can be a powerful tool to not only put diabetes into remission, but also to decrease the risk of developing diabetes later on.  Earlier intervention is better, because the longer a person has diabetes, the more tired their pancreas gets (ie decreased beta cell function, which are the cells that produce insulin), and a tired pancreas may be too tired to control blood sugars after bariatric surgery without help from medication.  Thus, considering bariatric surgery early in the course of diabetes, or even in the prediabetes phase, may have the most powerful impact.

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www.drsue.ca © 2017

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Mental Health and Bariatric Surgery - Canadian Data

We know that there is a relationship between mental health and obesity, with mental health issues such as depression being associated with an increased risk of obesity, and with the risk of mental health issues developing increasing as weight increases. In people with more pronounced obesity who are considering bariatric surgery as a treatment option, it is important to consider how mental illness may impact the efficacy and safety of surgical treatment for obesity.

These issues were beautifully summarized in a recent review by Val Taylor and colleagues, published in the Canadian Journal of Diabetes, with a focus on Canadian data.

Here are a few of the highlights:

1. How common are mental health issues in Canadian bariatric surgery patients? 

Over half of patients presenting in Ontario for bariatric surgery had a history of mental illness (most commonly depression). Neither a history of depression nor bipolar disorder seem to be associated with success of weight loss with bariatric surgery, but stability and control of mental health issues preoperatively is important to optimize success.  The prevalence and severity of depression in the bariatric population are consistently decreased after surgery – but there is a risk of development of depression for some people as well, which may be related to some of the psychological challenges that can present after surgery.  Many people with mental health issues are taking medications to treat these conditions, and absorption of these meds may be affected after surgery, so close monitoring to ensure good control of the mental health issue after surgery is important.

2. Eating disorders:

Binge eating disorder (BED) has a prevalence of up to 30% in people presenting for bariatric surgery, with the data conflicting on whether BED reduces the success of weight loss with bariatric surgery. Management of the feeling of loss of control and regulation of emotions in these individuals are important factors to help reducing binge eating in this group.

Active bulimia is a contraindication to bariatric surgery.

3. Suicide risk:

While depression usually improves after surgery, the risk of suicide is increased after bariatric surgery, with a multitude of possible reasons/contributors behind this fact.  The risk of self harm seems to be increased at least 3 years after surgery, so long term psychological follow up and support of bariatric patients is essential.

4. What if there is a past history of sexual abuse?

A history of sexual abuse is present in 21.5% of people in the Ontario Bariatric Surgery Registry.  While this does not appear to influence the success of surgery, these individuals are at a higher risk of mental health issues such as depression, speaking to the need for proper assessment and follow up.

5.  Substance use/abuse:

A history of substance use (alcohol, tobacco, or recreational/illicit drugs) seems to be correlated with a risk of substance use after surgery, particularly if the substance use history is near to the time of surgery.  Alcohol abuse is a particular risk, as alcohol hits harder and fasterafter surgery.  A ‘transfer’ of addictions from one thing to another (eg, from food to gambling) after surgery has been described, and should be discussed and managed ahead of time.

Most often, mental health issues can generally be well managed to optimize success of the individual undergoing bariatric surgery.  Identifying and managing these issues before surgery is essential, and long term support after surgery is key as well.

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www.drsue.ca © 2017

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Blood Sugar and Insulin Levels As A Biomarker For Weight Loss Success?

To date, no particular diet composition has been shown to be superior to another for weight loss success in the general population.  However, we haven't yet ruled out that some types of diets may work better for certain specific groups of people.  For the first time, a new study suggests that people with prediabetes or diabetes, and people with higher fasting insulin levels, may have better weight loss success with either a lower glycemic load diet, or a diet containing a large amount of fiber and whole grains.

The study, published in the American Journal of Clinical Nutrition, evaluated data from three studies and stratified weight loss results by fasting blood sugar and insulin levels.

The first trial, called the DioGENES study (as blogged previously), looked at the ability to maintain weight loss using a high vs low glycemic index and high vs lower protein diet.   The results of this study overall showed that a low GI, higher protein diet was superior to a high GI, lower protein diet to maintain lifestyle-induced weight loss.  In the current analysis, they found that people with prediabetes regained 5.83kg more on a high GI diet than a low GI diet, whereas people with normal blood sugar regained only 1.44kg more on a high GI diet than a low GI diet.

The second study, called the SHOPUS study, was designed to test the New Nordic Diet, which is high in fiber and whole grains. People with prediabetes lost a mean of 6 kg on this diet, whereas people with normal blood sugars lost only 2.2kg.

Finally, in the NUGENOB study, which was designed to test nutrient-gene interactions in obesity, people with diabetes lost a mean of 2kg more on the high fat/low carb diet than on the low fat/high carb diet, whereas people with normal sugars lost only 0.43kg more on the above comparison.

When the authors incorporated fasting insulin levels into these analysis, the associations above were strengthened further.  Some interesting phenotypes were also revealed:

• people with lower fasting blood sugar and high fasting insulin levels responded equally on all 3 pairs of diets 
• people with high fasting sugars and low fasting insulin levels did better on diets with a lower glycemic load and more fiber and whole grains
• people with lower blood sugar and lower fasting insulin did better on a low fat/high carb diet. 

We often talk about precision medicine - customization of health care decisions based on each individual's genetics, lab results, hormone levels, and so on; yet in obesity medicine, we have very little routinely measured information that can help us determine what type of management program may be best for our patient.  Finally we have some data, using easily measurable blood tests, that may help to guide us.

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www.drsue.ca © 2017

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Obesity, Addiction, Alcohol and Bariatric Surgery Part II

We know that the factors behind each individual's struggle with obesity are unique, with a long list of physiologic, psychological, and environmental factors as potential contributors.  We are also learning increasingly that there are many areas of neurophysiologic (brain), psychological and behavioral overlap in the realms of obesity and addiction.

In part I of this two-part blog post, we discussed some of the changes that happen after bariatric surgery, as discussed in a recent review.

Now, some threads that weave a connection for some people between obesity and addiction: 

1.  For some people, food is an addictive substance.  People who have high scores on food addiction questionnaires have similar patterns of brain activation as in people with other addictions.  Also, overconsumption of certain nutrients (eg sugar) elicits chemical responses in our brains, similar to those that result from consumption of drugs or alcohol.

Some people think that combatting a food addiction is no different than trying to quit smoking.  But remember, a person who quits smoking can (and ideally will) lead their life without ever touching another cigarette.  But the person battling a food addiction can't stop eating - they have to continue to eat for the rest of their lives, while controlling the addictive component that leads to overeating: a very, very difficult thing to do. 

2.  Some people with obesity have more 'turbo-charged' food reward circuits in their brains, which results in a powerful drive to seek high calorie food.  Obesity can also be accompanied by a reduced brain-driven ability to resist temptation and control impulses to eat, with data suggesting that there is a genetic component to these differences.  After gastric bypass surgery, research has identified some changes in this brain activity, and these changes may be associated with the amount of weight lost after surgery.

Know that feeling of: I am so hungry I don't care what it is it just has to happen RIGHT NOW...?
For some people, this feeling may come only if meals are skipped for many hours, or after a fierce workout.  For others, they may feel like this until their body is at a higher body weight 'set point'.  The level of energy reserves, or time from last meal that contributes to the threshold for this feeling to set in, is very different from person to person.

So for people who have a food addiction, as well as for people who have a more powerful reward circuitry, weight management will be difficult, but not impossible - having a psychologist with professional training in obesity management is an important part of the team to help manage their weight struggles.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2017

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