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Sleep Restriction Leads To Less Fat-Loss

Regular readers will be well aware of the increasing data supporting the importance of adequate restorative sleep on metabolism and weight management.

Now, a study by Wang Xuewen and colleagues, published in SLEEP, shows just how detrimental sleep deprivation can be during a weight-loss diet.

Their study included thirty-six 35-55 years oldadults with overweight or obesity, who were randomized to an 8-week caloric restriction (CR) regimen alone (n=15) or combined with sleep restriction (CR+SR) (n=21). All participants were instructed to restrict daily calorie intake to 95% of their measured resting metabolic rate. Participants in the CR+SR group were also instructed to reduce time in bed on 5 nights and to sleep ad libitum on the other 2 nights each week.

The CR+SR group reduced sleep by about 60 minutes per day during sleep restriction days, and increased sleep by 60 minutes per day during ad libitum sleep days, resulting in a sleep reduction of about 170 minutes per week.Although both groups lost a similar amount of weight during the study ~3 Kg). However, the proportion of total mass lost as fat was significantly greater  in the CR group (80% vs. 16%).

In line with this substantial difference in fat reduction, resting respiratory quotient was significantly reduced only in the CR group.

Importantly, these effects of sleep deprivation on fat loss were observed despite the fact that subjects were allowed to sleep as much as they wanted on the non-restricted days. This suggests that the negative effects of sleep deprivation during weight loss are not made up by “make-up” sleep.

Although overall, the amount of weight lost in this study is modest, it clearly fits with the notion that adequate sleep (in this case, during weight loss), can be an important part of weight management.

Clearly, the role of sleep in energy homeostasis will remain an interesting field of research, as we continue learning more about how sleep (or rather lack of it) affects metabolism.

Edmonton, AB


Semaglutide Continues To Hold Promise For Obesity Treatment

This week, the Lancet published the results of the SUSTAIN7 trial, an open-label, parallel-group, phase 3b trial done at 194 hospitals, clinical institutions or private practices in 16 countries.

Eligible patients with type 2 diabetes (HbA1c 7·0–10·5% on metformin monotherapy, n=1201), were randomised to once-weekly injections of the GLP-1 analogues semaglutide 0·5 mg, dulaglutide 0·75 mg, semaglutide 1·0 mg, or dulaglutide 1·5 mg.

Over the 40 weeks of treatment, participants on semaglutide had a greater reduction in HbA1c than participants who were on corresponding doses of dulaglutide.

More interesting, in the context of this blog, semaglutide was also almost twice as effective in lowering mean body weight than dulaglutide.

Thus, bodyweight was reduced by 4·6 kg with semaglutide 0·5 mg compared with 2·3 kg with dulaglutide 0·75 mg and by 6·5 kg with semaglutide 1·0 mg compared with 3·0 kg with dulaglutide 1·5 mg.

As expected, the most frequent adverse effects were gastrointestinal.

Given that this was not actually a trial designed to maximise weight loss (as would have been attempted in a study primarily designed to study semaglutide as a treatment for obesity), these changes in body weight are certainly quite impressive.

These findings no doubt hold promise for the further development of semaglutide as an anti-obesity medication.

Edmonton, CA
Disclaimer: I have received speaking and consulting honoraria from Novo Nordisk, the maker of semaglutide


New European Guidelines on Medical Management After Bariatric Surgery

The European Association for the Study of Obesity (EASO) had now released the new OMTF guidelines Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for Post-Bariatric Surgery Medical Management.

The guidelines provide the latest guidance on nutritional management, micronutrient supplementation, managing co-morbidities, pharmacotherapy, psychological management, and prevention and management of weight regain. The guidelines also address the issue of post-bariatric surgery pregnancy.

Not covered are issues related to dealing with excess skin and rehabilitation (e.g. return to work, reintegration in social activities, education, etc.), both of significant importance, especially in people with severe obesity.

As the authors note,

“Bariatric surgery is in general safe and effective, but it can cause new clinical problems and it is associated with specific diagnostic, preventive and therapeutic needs. Special knowledge and skills of the clinicians are required in order to deliver appropriate and effective care to the post-bariatric patient. A post-bariatric multidisciplinary follow-up programme should be an integral part of the clinical pathway at centres delivering bariatric surgery, and it should be offered to patients requiring it”

These guidelines are now available open access in Obesity Facts.

Edmonton, AB


Reducing Cardiovascular Risk In Adolescents With Bariatric Surgery

Given the limited effectiveness of “lifestyle” interventions and the lack of access to medical treatments, many adolescents struggling with severe obesity are left with no option but to consider having bariatric surgery.

Now, a paper by Marc Michalsky and colleagues on behalf of the Teens LABS Consortium, in a paper published in Pediatrics, describes the effect of bariatric surgery on cardiovascular risk factors in adolescents undergoing these procedures.

The study includes 242 adolescents (76% girls, 72% white, mean age 17 ± 1.6 y,  median BMI 51) undergoing bariatric surgery (Roux-en-Y gastric bypass (n = 161), vertical sleeve gastrectomy (n = 67), or adjustable gastric banding (n = 14)), at five centers.

At 3 years following surgery, weight was significantly lower in all groups (28%, 26%, and 8% for RYGB, VSG, and AGB, respectively).

Hypertension, observed in 44% of participants, declined to 15% at 3 years.

Dyslipidemia observed in 75% of participants, declining to 27% by 1 year and 29% by 3 years. This improvement was largely due to decrease in triclycerides and increases in HDL cholesterol.

Baseline diabetes was present in 13% of participants with major metabolic improvement (0.5%) by 3 years. Similarly, baseline impaired fasting glucose (26%) and hyperinsulinemia (74%) dramatically improved by year 3 (4% and 20%, respectively).

Improvements in these parameters were related to the degree of weight loss.

Remission rates were negatively correlated to higher age and positively correlated to female sex and white race.

Overall, the authors conclude that this study documents the improvements in cardiovascular risk factors in adolescent bariatric surgery.

Unfortunately, the study does not present any information on surgical complications or reoperation rates, an obvious matter of concern when it comes to surgery in this young population.

While there may well have been no alternative to surgical treatment in these kids, we can only hope that eventually medical treatments will become available for this population, hopefully with similar outcomes. Unfortunately, that may well still be a long way off.

Edmonton, AB


Molecular Changes During Weight Gain – Everyone Is Different

As one may well imagine, changes in body weight (up or down) can profoundly affect a vast number of hormonal and metabolic pathways.

Now, a team of researchers led by Brian Piening and colleagues, in a paper published in Cell Systems used a broad “omics” based approach to study what happens when people lose ore gain weight.

Specifically, the goal of this study was to:

(1) assemble a comprehensive map of the molecular changes in humans (in circulating blood as well as the microbiome) that occur over the course of a carefully controlled weight gain and their reversibility with weight loss; and

(2) determine whether inulin sensitive (IS) and insulin resistant (IR) individuals who are matched for degree of obesity demonstrate unique biomolecular signatures and/or pathway activation during similar weight gain.

The study included 23 carefully selected healthy participants with BMI 25–35 kg/m2, were studied. Samples were collected at baseline. They then underwent a 30-day weight gain period (average 2.8 kg), followed by an eucaloric diet for 7 days, at which point a second fasted sample of blood and stool was collected. Each participant then underwent a caloric-restricted diet under nutritionist supervision for a subsequent 60-day period designed to return each participant back to his/her initial baseline weight, at which point a third set of fasted samples of blood and stool were collected. A subset of participants returned for a follow-up sampling approximately 3 months after the end of the perturbation.Insulin resistance was assessed at baseline using a modified insulin suppression test.

The large-scale multi-omics assays performed at all time points on each participant included genomics, proteomics, metabolomics and microbiomics.

Despite some differences between the IS and IR group (particularly in differential regulation of inflammatory/immune response pathways), overall, molecular changes were dominated by inter-personal variation (i.e. changes within the same individual), which accounted for more than 90% of the observed variance in some cases (e.g., cytokines). The most striking changes with weight gain were in inflammation response pathways (despite the rather modest weight gain) and were (fortunately) reversed by weight loss.

As the authors note,

“Comparing the variation in cytokine levels between multiple baselines in a single individual versus across individuals, we observed a striking difference: for almost all cytokines, the within-individual coefficient of variation was under 20%, whereas the variation across individuals was 40%–60%. This shows that our baseline cytokine profiles are unique to the individual, a point that has significant implications for one-size-fits-all clinical cytokine assays for the detection and/or monitoring of disease.”

On the opposite side of the spectrum, proteomics and metabolomics measurements had a substantial unexplained component (30% and 35%, respectively), highlighting the presence of unaccounted factors (e.g., food, exercise, and other changing environmental factors) or a subject-specific reaction to the perturbation.

Notably, not all of the responses we observed were consistent across IR and IS participants.

“In particular, for the microbiome, we observed that the microbe A. muciniphila was weight gain responsive only in insulin-sensitive participants. The abundance of this particular microbe in IR individuals did not change across perturbations and was barely or not detectable in most IR individuals.”

Clearly, these findings highlight the fact that each individual is biochemically unique, which the authors note, makes a strong case for personalized analysis in medicine.

Perhaps more importantly for researchers, nearly all of the data are publicly available, enabling exploration of inter-omic relationships and alterations across a longitudinal perturbation, thus providing a valuable resource for the development and validation of bioinformatic tools and pipelines integrating disparate data types.

Edmonton, AB