1/ WHAT YOU NEED TO KNOW ABOUT THE QUALITY OF WEIGHT LOSS. 🧵 2/ When you lose weight, you don’t just lose from fat but also from other body compartments, including lean tissues.

1/ Are lean mass losses a real concern with GLP1 meds?
peterattiamd.com/the-downside-o…
🧵 2/ Simply, yes. And it is a concern any time you lose significant wt. I would remind people that human outcomes are the most informative, as physical functioning scores and QoL improved in STEP trials & SURMOUNT-1. However, the LT health impacts of LM loss need to be monitored.

1/ Merry 🧵-mas
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WHY DECADES OF "EAT LESS AND MOVE MORE" WAS TERRIBLE ADVICE

For starters, remember semaglutide? How could you not? Journalists have written 1000+ celebrity weight loss stories on it. 2/ If you're familiar with semaglutide, you may know it is FDA-approved for treating obesity and chronic weight management under the brand name "WE-GOVY."

NASH Treatment Strategies:
1) Reduce Adiposity
2) Improve adipose tissue function (more difficult; PPARg agonists) link.springer.com/article/10.100…

Treat-to-target for NAFLD/NASH:
🔑 is ≥ 10% weight loss.
journal-of-hepatology.eu/article/S0168-… Bariatric surgery is exceedingly effective for people with obesity and NASH.
Aminian et al., JAMA. 2021.
jamanetwork.com/journals/jama/…

1/DAY 1 of #OW2022 in the books.

My highlight 🧵: 2/The Effect of COVID on Clinical Research by Drs. Laughlin and Evans:
—Significant increase in new onset diabetes
—A lot of COVID specific research for years to come
—COVID19 disproportionately impacted female scientists, parents and caregivers #OW2022

My living 🧵 on the highlights from 'Causes of obesity: theories, conjectures and evidence.' #RScausesobesity
@royalsociety

Link: causes-obesity.royalsociety.org DAY 1 -- From genetics to nutrient-dependent conditioned eating, variable mitochondrial energy efficiency, neuroendocrine feedback systems, and nutrient-sensing food liking, obesity is very clearly more complicated than CICO. Energy balance is a constraint, that is all.

1/Bariatric surgery is often described as "barbaric" and "radical." I believe most of these polarizing opinions are derived from ignorance, so let's explore the science of bariatric surgery to better understand what is happening. 🧵 2/The greatest misconception is that surgery works through the "radical mutilation of the small intestine" or that wt loss is 2/2 to malabsorption.

In fact..."extensive small bowel resection is associated with a compensatory increase in food intake." Cosnes et al., 1990 h/t LK

While GLP1 therapies primarily exert their weight loss effect through a reduction in food intake, I’m increasingly convinced the most important mechanism behind the decrease in Ein is an attenuation of motivation-reward. I suspect homeostatic modulation plays a smaller role LT. Mind you that this is speculative, but as my friend, @DavidMacklinMD often says, all roads lead to hedonic hunger. Do you WANT to eat? Are you compelled? Most people describe having better control, less interest, and a lack of compulsion while on GLP1s. It’s hedonics!

1/ NOT THE THREAD DIGITAL HEALTH WANTS TO READ, BUT THE THREAD IT NEEDS TO READ. Walk with me…🧵 2/ Many people know about the darling of digital health — Livongo. Arguably the highest profile digital health company ever due to an $18.5 billion dollar merger with Teladoc back in 2020. medcitynews.com/2020/10/telado…

Why is losing weight hard? Evolutionary adaptations to prevent starvation and death constrain weight loss. Conversely, hypothalamic inflammation can promote wt gain affecting the fxn of the homeostatic feedback system that constrains wt.
-Dr. Katherine Saunders #YWM2022Virtual Weight Loss Goal? Not a number but a health improvement. With modern treatments, I would argue we should aim for 10% TBWL. #YWM2022Virtual

"If someone has myopia, you wouldn't tell them to try harder to see. You would not shame them for needing glasses." -Lee Kaplan

Yet, in obesity, we shame people for seeking evidence-based treatments and implore them "to eat less and move more" harder. #YWM2022Virtual The legacy bias in bariatric surgery qualification #YWM2022Virtual

1/ STEP 4 Trial of Semaglutide for obesity treatment is a beautiful illustration of the physiology of body weight regulation. Let's explore it in this 🧵 2/ First off, all study participants "received open-label once-weekly subcutaneous semaglutide, 0.25 mg, increased every 4 weeks to the maintenance dose of 2.4 mg once weekly by week 16, and continued to week 20."

1/ Understanding Obesity Pathophysiology Through Outcomes:

IMO, the limitations of these surrogate measures (fMRI & PET), make outcome studies a more reliable insight for understanding obesity mechanisms.

A [thread] on outcomes for clinical interventions for obesity. 🧵

https://twitter.com/TheMooreLab/status/1505419727593689090

2/ Do Diets Matter? Yes and No. They matter because you have to eat, and you want to do so in a way that promotes health. But, are they reliable txs for obesity? No. Meta-analysis of long-term RCTs (avg wt loss 0-4 kg). Most intensive diet interventions result in 3-5% wt loss.

1/ Is Obesity A CHOICE?

The thread 🧵. For starters, please answer the following question ⬇️ 2/ So Why We Are Gaining Weight? Unquestionably, we are eating more, and this increased consumption at a population level is the leading candidate.

1/ It is no surprise that Semaglutide is the bell of the pharmacotherapy ball. Let's review some key takeaways from the STEP trials to understand why SEMA 2.4 mg is so exciting.
*credit to Dr. Wadden. #OW2021

STEP 3 2/ Intervention: Intensive Behavioral Therapy + Low Calorie Diet +/- SEMA 2.4 mg #OW2021

1/ Circadian Fasting: by Dr. Chow
The theme of the day => TRE researchers have a lot to say about @ethanjweiss's research. #OW2021 2/ Eating in the AM is possibly more satiating. #OW2021

1/ Dr. Lee Kaplan: What Does the Future of Obesity Care Look Like? #OW2021

Every time I hear Dr. Kaplan speak, I am blown away by his knowledge and perspective. He, once again, delivered a masterclass on obesity.

Point #1: We are undertreating obesity Point #2: An active, involuntary physiological system determines body fatness at any one time. #OW2021

1/ Future of Obesity Treatments? #OW2021

Meet the candidates:
1) AM833 +/- Semaglutide 2.4 mg; combo therapy resulted in 15-17% at 20 weeks with no evidence of nadir, suggesting even greater wt loss (likely >20%).
by Dr. Rubino 2/ Tirzepatide; hard to imagine a future without tirzepatide (as long as safety & tolerability remain) for the treatment of metabolic dz when >10% wt loss and -2.5% A1c are avg results. Also, >50% of participants achieved normoglycemia with most doses‼️
↪️by Dr. Frias #OW2021

“Obesity is a choice” is the biggest misconception we tell ourselves and our patients. Read any of the genetics or neuroscience of obesity literature, and you would quickly rid yourself of this concept. Ignorance remains an obstacle to progress. Notably, personal responsibility still matters. It is the difference between learned helplessness and learned optimism. You do not have to be a victim. And we could do all this while appreciating that some aspects of our environment and biology are outside of our control.

Why you should consider a career in Obesity Medicine:

Reason #1: Essentially No Call

Yes, I occasionally have to decrease insulin because a patient’s glycemic control is improving too rapidly. I know! It’s a terrible problem to have. Reason #2: Medication Deprescribing

How many of you get to routinely stop BP, Diabetes, antidepressants, and pain meds? Deprescribing is the new prescribing.