Human Hypothalamic Obesity
The second day of the 21st Europena Congress on Obesity in Sofia, Bulgaria, featured a plenary talk by Herman Mueller from Oldenburg, Germany, on the important lessons to be learnt from human forms of hypothalamic obesity.
As readers are well aware, the hypothalamus is the key region in the brain for the regulation of energy balance – through its influences both on hunger and satiety as well as energy expenditure.
The best example of severe obesity caused by damage to the hypothalamus comes from patients with craniopharyngoma, a tumour that can partially or fully destroy the hypothalamus.
Indeed, craniopharyngoma are the most common form of sellar tumours.
Mueller presented his findings from a series of over 300 patients with craniopharyngoma recruited from Germany, Austria and Switzerland.
About half of the patients with craniopharyngoma develop severe obesity, whereas the other half maintain normal body weights.
It turns out that obesity may be one of the first signs of craniopharyngoma in children, sometimes preceding the diagnosis of this problem by over 24 months.
As expected, quality of life significantly reduces the quality of life in patients with hypothalamic obesity.
Interestingly, Mueller was unable to find marked differences in energy intake in patients with craniophyrongoma. Rather, accelerometric studies demonstrated reduced physical activity, increased daytime sleepiness and reduced night-time melatonin levels.
In fact, many of these patients had severe dysregulation of sleep cycles, which may in turn have contributed to weight gain.
Unfortunately, systematic study of this issue is complicated due to the fact that most centres see very few cases of this rather rare tumour.
Mueller emphasized that once hypothalamic obesity is established in patients with hypothalamic involvement, obesity becomes lifelong even if the tumour is fully surgically resected.
Thus, Mueller warns agains “radical” surgery in individuals without hypothalamic involvement to avoid damaging the hypothalamus.
With regard to treating severe obesity in patients with craniopharyngoma, Mueller notes that surgery may provide some relief. He described the case of a patient with severe hypothalamic obesity, who responded favourably to adjustable gastric banding, although not all patients experience sustainable weight loss. Nevertheless, the best results have been reported for gastric bypass and sleeve gastrectomy, although data on long-term follow-up remains scarce.
As for medical and behavioural therapy, Muellar was less optimistic – his extensive review of these studies showed rather modest and inconsistent results, often limited by side effects.
As for future interventions, one will need to await further developments in the pharmacological management of obesity and perhaps more radical treatments such as deep brain stimulation.
@DrSharma
Sofia, Bulgaria
Gut Bugs Play Central Role in European Obesity Congress
I am currently attending the 21st European Congress on Obesity in Sofia, Bulgaria, where the opening plenary talk was given by Karin Clement on gut microbiota-host interactions in obesity.
As a regular reader, you are probably well aware of the fast-evolving research on this issue, suggesting that the bugs that live in your gut may have a causal role to play in the development of obesity.
Indeed, there is now abundant evidence that obesity, both in animal models and humans, is very much related to variations in gut bug populations and diversity.
There is also considerable evidence to suggest that, rather than this being a mere consequence of excess weight, these differences may well play a causal role in the development of excess weight gain.
In her talk, Clement discussed the latest findings on how dietary interventions can results in a “healthier” pattern of gut bacteria, but she also emphasized that the differences in gut bugs found between obese and non-obese individuals cannot be explained by dietary patterns alone.
Clement also presented studies on gut bacteria changes seen in patients who underwent bariatric surgery.
Again, while patients with gastric-bypass surgery showed a marked change in gut microbial pattern, these changes were not fully explained by changes in dietary food intake.
Rather, it appears that bariatric surgery may exert some of its benefits through alteration of the gut bacteria.
Some of the most compelling data on the role of gut bacteria in obesity (and other metabolic problems) comes from fecal transplant studies in animals (and a few human studies).
Clearly, these findings open up a whole new avenue for obesity research, which may well lead to new approaches to manage obesity and related metabolic disorders.
@DrSharma
Sofia, Bulgaria
Hypertension: Cut The Sugar?
Anyone interested in blood pressure will have gotten the message that cutting salt may well be beneficial, especially in someone who has high blood pressure.
Indeed, there is little doubt that a substantial proportion of the population (although not everyone), may be “salt-sensitive” (this used to be my area of research before I switched to obesity).
Now, a paper by Lisa Te Morenga and colleagues, in a paper published in the American Journal of Nutrition, suggests that sugar may be as (if not more) potent than salt in increasing blood pressure levels.
The researchers conducted a systematic review and meta-analysis of 12 randomized controlled trials that examined effects of the modifying dietary free sugar on blood pressure and found that increased sugar intake could increase systolic and diastolic blood pressure by almost 7 and 6 mmHg, respectively – this effect was greatest in trials ≥8 wk in duration and was not explained by a change in body weight.
This is certainly impressive, as these numbers even exceed what is generally quoted for blood pressure effects of sodium.
While no convincing explanation for the biological basis for these findings are given, they are indeed intriguing as these are findings from randomised intervention trials in human volunteers. No doubt, these findings are certainly far more convincing than the usual “‘X’ causes ‘Y'” nonsense, that we so often see derived from epidemiological studies.
Given the current “moral panic” about sugar (which has pretty much replaced the previous “moral panic” about fat), it should not be hard to get funding to figure out how this actually works.
@DrSharma
Sofia, Bulgaria
Te Morenga LA, Howatson AJ, Jones RM, & Mann J (2014). Dietary sugars and cardiometabolic risk: systematic review and meta-analyses of randomized controlled trials of the effects on blood pressure and lipids. The American journal of clinical nutrition PMID: 24808490
What’s Europe Doing About Obesity?
As I head out to attend the 21st European Congress on Obesity in Sophia, Bulgaria, I came across this interactive site that allows interested readers to checkout obesity interventions across Europe.
The atlas of European projects and interventions for obesity prevention in adults is part of the SPOTLIGHT project which udertook a Europe-wide survey to provide an overview of projects and interventions to prevent adult obesity through improving diet and physical activity.
While the atlas may not include every single intervention that is currently happening, it does provide a sense of the scope and range of these activities.
For each project or intervention the atlas considers the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) aspects and presents these data where available.
I am sure I will have plenty more to report on based on what I hear at the conference.
@DrSharma
Munich, Germany
Does Short-Term Weight Loss Reduce Cardiovascular Risk?
If you believe recent media headlines describing the findings of a paper published in The Lancet last week, you may be convinced that any weight loss – even if you don’t keep the weight off – reduces your risk for cardiovascular disease.
The study, reports on the relationship between lifelong patterns of BMI and cardiovascular risk a 60-64 year-old British birth cohort born in 1946.
Participants were classified as normal weight or overweight or obese based on heights and weights measured during childhood (at ages 2, 4, 6, 7, and 11 years) and adulthood (at ages 36, 43, 53 and 60–64 years).
As may be expected, various measures of cardiovascular and metabolic risk factors were positively related to extent and duration of adiposity.
There were, however, two findings that may seem rather unexpected:
Firstly, adiposity in childhood did not seem to matter as a predictor of CV risk in adulthood.
Secondly, it appeared that individuals who dropped at least one BMI category at any time during adulthood, irrespective of whether or not this weight loss was maintained, had lower cardiovascular (but not diabetes) risk than did those who never lost weight.
From these findings the authors conclude that,
“…cardiovascular benefit might arise from weight loss in adulthood, irrespective of when this weight loss is achieved, and support public health policies for lifestyle modifications for prevention and management of overweight and obese individuals at all ages.“
While it is easy to see why sustaining weight-loss as an adult (particularly if you have risk factors for cardiovascular disease) may well be beneficial, it is hard to imagine a plausible biological pathway that would link a “short-term” weight loss to long-term improvements in cardiovascular risk.
Indeed, the authors provide no explanation for their findings. They also provide no further information on the people who lost weight compared to the people who did not.
My first response would be to look for biological plausible confounders – were people who lost weight at anytime as adults perhaps more conscious or concerned about their health than those who did not? Or, were they more metabolically healthy to start with?
Let us also not forget that this was merely an observational study – association does not prove causality.
This is not to say that the findings are entirely implausible. There is some literature on the long-term “legacy effect” of lifestyle interventions on metabolic risk factors – but the biological basis for this is unknown and some colleagues doubt wether this effect really exists.
Given that weight regain is rather common after weight loss, it will be interesting to see if other studies can demonstrate lasting benefits of short-term weight loss.
At this time some scepticism may well be warranted.
@DrSharma
Edmonton, AB