The biguanide metformin is widely used for the treatment of type 2 diabetes. Metformin has also been shown to slow the progression from pre to full-blown type 2 diabetes. Moreover, metformin can reduce weight gain associated with psychotropic medications and polycystic ovary syndrome.
Now, a randomised controlled trial by M P van der Aa and colleagues from the Netherlands, published in Nutrition & Diabetes suggests that long-term treatment with metformin may stabilize body weight and improve body composition in adolescents with obesity and insulin resistance.
The randomised placebo-controlled double-blinded trial included 62 adolescents with obesity aged 10–16 years old with insulin resistance, who received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months.
Of the 42 participants (mean age 13, mean BMI 30), BMI was stabilised in the metformin group (+0.2 BMI unit), whereas the control group continued to gain weight (+1.2 BMI units).
While there was no significant difference in HOMA-IR, mean fat percentage reduced by 3% compared to no change in the control group.
Thus, the researcher conclude that long-term treatment with metformin in adolescents with obesity and insulin resistance can result in stabilization of BMI and improved body composition compared with placebo.
Given the rather limited effective options for addressing childhood obesity, this rather safe, simple, and inexpensive treatment may at least provide some relief for adolescents struggling with excess weight gain.
Continuing in my miniseries on arguments that support calling obesity a disease, is the simple fact that, once established, it behaves like a chronic disease.
Thus, once people have accumulated excess or abnormal adipose tissue that affects their health, there is no known way of reversing the process to the point that this condition would be considered “cured”.
By “cured”, I mean that there is a treatment for obesity, which can be stopped without the problem reappearing. For e.g. we can cure an ear infection – a short course of antibiotics and the infection will resolve to perhaps never reappear. We can also cure many forms of cancer, where surgery or a bout of chemotherapy removes the tumour forever. Those conditions we can “cure” – obesity we cannot!
For all practical purposes, obesity behaves exactly like every other chronic disease – yes, we can modify the course or even ameliorate the condition with the help of behavioural, medical or surgical treatments to the point that it may no longer pose a health threat, but it is at best in “remission” – when the treatment stops, the weight comes back – sometimes with a vengeance.
And yes, behavioural treatments are treatments, because the behaviours we are talking about that lead to ‘remission’ are far more intense than the behaviours that non-obese people have to adopt to not gain weight in the first place.
This is how I explained this to someone, who recently told me that about five years ago he had lost a substantial amount of weight (over 50 pounds) simply by watching what he eats and maintaining a regular exercise program. He argued that he had “conquered” his obesity and would now consider himself “cured”.
I explained to him, that I would at best consider him in “remission”, because his biology is still that of someone living with obesity.
And this is how I would prove my point.
Imagine he and I tried to put on 50 pounds in the next 6 weeks – I would face a real upward battle and may not be able to put on that weight at all – he, in contrast, would have absolutely no problem putting the weight back on.
In fact, if he were to simply live the way I do, eating the amount of food I do, those 50 lbs would be back before he knows it.
His body is just waiting to put the weight back on whereas my biology will actually make it difficult for me simply put that weight on.
This is because his “set-point”, even 5 years after losing the weight, is still 50 lbs higher than my “set-point”, which is around my current weight (the heaviest I have ever been).
Whereas, he is currently working hard against his set-point, by doing what he is doing (watching what he eats, following a strict exercise routine), I would be working against my set-point by having to force myself to eat substantially more than my body needs or wants.
That is the difference! By virtue of having had 50 lb heavier, his biology has been permanently altered in that it now defends a weight that is substantially higher than mine.
His post-weight loss biology is very different from mine, although we are currently at about the same weight.
This is what I mean by saying he is in “remission”, thanks to his ongoing behavioural therapy.
Today, we understand much of this biology. We understand what happens when people try to lose weight and how hard the body fights to resist weight loss and to put the weight back on.
This is why, for all practical purposes, obesity behaves just like every other chronic disease and requires ongoing treatment to control – no one is ever “cured” of their obesity.
Not even people who have bariatric surgery – reverse the surgery and before you know it, the weight is back.
So, if for all practical purposes, obesity behaves like a chronic disease, why not just call a spade a spade?
For an illustration on why obesity acts like a chronic disease watch this short TEDx talk
Are you an impulsive eater? Do you have a hard time meal planning or keeping a food journal? Do you find it hard to remember if you had breakfast or not (never mind what you actually ate)? Do you start every new diet or exercise program with super enthusiasm, only to lose interest a few days later? Does your day lack a routine (for no good reason)?
These are just some of the ways in which Attention Deficit Hypertactivity or just Attention Deficit Disorder (ADHD/ADD) can sabotage your efforts to control your weight.
Now, an article by Philip Asherson and colleagues from Kings College London, UK, published in The Lancet Psychiatry discuss important conceptual issues regarding the diagnosis and management of ADHD/ADD in adults.
Although ADHD/ADD is largely thought to be a problem in kids and youth, it remains a considerable and often undiagnosed issue in adults.
Thus, as the authors point out,
“…treatment of adult ADHD in Europe and many other regions of the world is not yet common practice, and diagnostic services are often unavailable or restricted to a few specialist centres.”
This is all the more surprising (and disappointing) given that adult patients respond similarly to current drug and psychosocial interventions, with the same benefits seen in children and adolescents.
With regard to diagnosis it is important to note that,
“Symptoms of ADHD cluster together into two key dimensions of inattention and hyperactivity-impulsivity, are reliably measured, and are strong predictors of functional impairments, but they reflect continuous traits rather than a categorical disorder.”
“Of particular relevance to adult ADHD is the relative persistence of inattention and improvements in hyperactive-impulsive symptoms during development, so that many patients who had the combined type presentation of ADHD as children present with predominantly inattentive symptoms as adults.”
“In clinical practice, the continuous nature of ADHD should not present diagnostic difficulties in moderate-to-severe cases, but might cause difficulties in mild cases with more subtle forms of impairment. Careful attention is needed to assess the effect of ADHD symptoms on impairment and quality of life, including an understanding of the broader range of problems linked to ADHD (eg, executive function [self-regulation] impairments, sleep problems, irritability, and internal restlessness), in addition to functional impairments such as traffic accidents and occupational underachievement. Therefore, some individuals, who seem to function well, might nevertheless suffer from a substantial mental health problem related to ADHD.”
Key criteria according to DSM-5 include:
- Mind seems elsewhere, even in the absence of any obvious distraction
- Starts tasks, but quickly loses focus and is easily side-tracked
- Fails to finish tasks in the workplace
- Reporting unrelated thoughts
- Problems returning calls, paying bills, keeping appointments
- Difficulty in managing sequential tasks; difficulty in keeping materials and belongings in order; messy, disorganised work
- Poor time management
- Tends to fail to meet deadlines
- Feeling restless
- Unable or uncomfortable being still for an extended time, such as in restaurants or meetings
- Might be perceived by others as being restless and difficult to keep up with
- Butts into conversations or activities, might start using other people’s belongings without permission, might intrude into or take over what others are doing
Other common features, that do not quite rise to level of diagnostic criteria include include poor concentration, distractibility, restlessness, over-talkativeness, sleep problems, irritability, impulsiveness, and low self-esteem.
It is important to note that other mental or physical disorders can mimic some of the symptoms of ADHD. These include anxiety, depression, bipolar disorder, hyperthyroidism and sleep apnea.
While the paper does not mention obesity or difficulties managing weight as a possible “complication” of ADHD, in my experience, identifying and treating ADHD in bariatric patients can often make all the difference.
Thus, I concur with the authors’ conclusions that,
“…ADHD should be recognised in the same way as other common adult mental health disorders, and that failure to recognise and treat ADHD is detrimental to the wellbeing of many patients seeking help for common mental health problems.”
The nature of chronic diseases is that they are (by definition) rarely (if ever) “cured”, meaning that the best you can generally hope for is “control”, which in some cases may only amount to “stabilisation” or “slowing of progression”.
In the context of obesity, one could perhaps define “control” as achievement AND maintenance of your “best weight”; “stabilisation” could be defined as prevention of further weight gain; “slowing of progression” would be defined as continuing to gain weight but at a slower rate than before.
Now, a paper by Janelle Coughlin and colleagues published in OBESITY, shows (surprise, surprise!) that continued intervention involving personal contact leads to better weight-loss maintenance (at five years) than time-limited self-directed management.
The paper describes the results of the the Weight Loss Maintenance (WLM) Trial, in which participants were essentially randomised to either a personal contact (PC) intervention or a self-directed (SD) group over 30 months with continued follow-up for another 30 months (for a total of 5 years).
Overall, the WLM had 3 phases. Phase 1 was a 6-month weight loss program. In Phase 2, those who lost ≥4 kg were randomized to a 30-month maintenance trial. In Phase 3, PC participants (n = 196, three sites) were re-randomized to no further intervention (PC-Control) or continued intervention (PC-Active) for 30 more months; 218 SD participants were also followed.
In the study overall at 5 years, mean weight change was −3.2 kg in those originally assigned to PC (PC-Combined) and −1.6 kg in SD (this rather modest amount of weight loss maintenance is unfortunately typical for all behavioural weight-management interventions, highlighting the ongoing need for better treatments!).
None of this is surprising.
As with any chronic disease, personal contact interventions by a trained health professional are likely to be superior to patients trying to manage on their own (self-directed).
At some point (the time may well be 30 months), continued regular intervention for everyone will likely provide diminishing returns.
This is evident from the finding in this study that in the PC group, continued intervention after 30 months did not appear to provide a significant additional benefit in terms of weight-loss maintenance.
In fact, one would probably want to vary frequency and intensity of any further intervention for patients who are relapsing (i.e. regaining their weight faster than expected).
This is not unlike patients in a diabetes or hypertension clinic. After an initial phase of a more intense intervention during which patients are titrated to a target blood pressure or HbA1c level, frequency of on-going follow-up should naturally be tailored to how well the patient in managing.
Some individuals will need more attention more often than others – this need will also be expected to vary over time for individual patients.
For many patients with chronic diseases, proper education and development of self-management skills (such as regular self-monitoring of blood pressure or blood sugar levels), may often allow on-going support to be limited to brief encounters largely involving brief assessments and prescription renewals.
As I have said before, long-term management of obesity is no different than managing any other chronic disease.
Tailoring the intensity and rate of follow-up to each patient’s specific needs should be no different in obesity management than in managing someone’s hypertension or diabetes.
Any follower of media reports or even research papers on the relationship between obesity and mortality should be righty confused by now.
Not only are there publications suggesting that the relationship between obesity and mortality isn’t that strong after all and that perhaps the BMI levels associated with the longest survival are somewhere around 30 (and not below 25) but then there is the issue of the obesity paradox, or the finding that among people with chronic (and some acute illnesses), a higher BMI is associated with better survival than being of “normal” weight.
On the other hand, there is overwhelming evidence that higher BMI’s are associated with an increased risk of a wide range of health problems – from diabetes to cancer.
This is not to say that everyone with a higher BMI is sick – they are not! But there is no doubt that the risk of illness does increase with higher BMIs.
In our own study on the Edmonton Obesity Staging System (EOSS), which classifies individuals based on their actual health rather on their BMI, we found that while about 50% of individual in the BMI 25-30 range can be considered healthy (EOSS Stage 0 or 1), this number drops to below 15% for individuals in the BMI 40+ range.
So, if obesity is such a risk factor for disease, why do epidemiological studies struggle to consistently show an effect of obesity on mortality?
Now, a paper by Andrew Stokes and Samuel Preston, published in the Proceedings of the US National Academy of Science, suggests that it is not current weight (as used in many studies) but rather the highest lifetime weight that is most clearly associated with mortality.
Their reasoning is as follows. “Intentional” weight loss in the population is rare (very few people in the general population ever consciously manage to lose a significant amount of weight and keep it off)
In contrast, “unintentional” weight loss, when it occurs is generally a bad sign. Indeed, one of the best indicators of poor prognosis (for almost any health condition) is when someone loses weight. In many cases, this “spontaneous” weight loss can precede overt illness or death by many years.
Thus, the authors argue that most of the literature on this issue is simply confounded by the confusion caused by all the people who have unintentionally lost weight due to an underlying health problem (diagnosed or undiagnosed).
As these people would be at higher risk of death, despite measuring in at a lower weight, they muddy the waters making lower BMI levels look more dangerous (or in comparison higher BMI levels look safer) than they are.
To test their hypothesis, the researcher looked at data from the US NHANES study linked to death registers using four different approaches:
Model 1: BMI measured at the time of survey (this is the method most commonly used in epidemiological studies)
Model 2: The highest reported lifetime BMI at the time of survey
Model 3: Individuals surveyed in their current BMI class who had never been heavier compared to individuals in that BMI class who reported formerly being in a higher BMI class.
Model 4: Individuals surveyed in their current BMI class compared to people who were formerly in that BMI class but had moved to a lower BMI class by the time of the survey.
In both models 1 and 2, there was a greater risk of mortality with higher BMI class, but the relationship was stronger in model 2 (highest lifetime BMI) than in model 1 (current BMI).
In model 3, there was still an increased risk with higher BMI class but within each current BMI class, risk was higher in individuals who had previously belonged to a higher BMI class.
In model 4, mortality also rose with the highest weight achieved but was markedly higher in individuals who lost weight after achieving a particular BMI category compared to those who remained at that maximum.
These findings have important implications for our understanding of the relationship between BMI and mortality.
As the authors note,
“Confining analytic attention to survey BMI alone thus sacrifices important information provided by an individual’s maximum BMI. The poor performance of the survey-only model is especially salient because models using only BMI at survey dominate the set of findings in the literature on the relation between BMI and mortality.”
The errors in not considering highest BMI are not trivial.
“33.9% of individuals in the sample who were normal weight at survey were formerly overweight, and this group had three times the prevalence of diabetes and cardiovascular disease CVD) relative to those who were in the normal-weight category at both max and survey.”
Here is how you would interpret the data,
“Disease prevalence and mortality both rise with increases in maximum BMI and rise even further for those who reach a particular maximum BMI category and then lose weight. These patterns strongly suggest that obesity raises the risk of diabetes and CVD and that, once acquired, these diseases often precipitate weight loss….Only by using weight histories can this pattern of erasure be identified and corrected.”
The use of historical data in determining risk would not be a new concept,
“The introduction of historical data in the analysis of smoking occurred more than a half century ago, when studies began to distinguish among current-, former-, and never-smokers.”
Similarly, in the context of obesity one would need to differentiate between people who currently have obesity, people who previously had obesity, and people who never had obesity.
All of this only works, because in these type of epidemiological studies, “intentional” weight loss, be it through behaviour change, medication or surgery, is so rare as to be non-existent. Virtually all weight loss seen at a population level in “unintentional” and probably related to underlying health issues.
Thus, one should not interpret these findings to mean that someone intentionally losing weight through behavioural, medical or surgical treatments is at a higher risk for mortality – the intervention studies we have on that (this cannot be studied in population studies as there are so few cases of “treated” obesity), suggest otherwise.
For clinicians, these data point to the importance of noting the highest BMI and not just current BMI – if the patient has lost weight (especially if this is not explained by obesity treatment), then this may be a high-risk patient.