Key quote:
"The RISK of developing obesity comes from genes."
Note that he doesn't say obesity itself is caused by genes. This would be an oversimplification!
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You've seen this graph in several versions. This is what happens when genes set a risk level and the environment selects for it, resulting in a specific phenotype
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The usual (known) monogene culprits. If you're studying for obesity boards, know these.
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An excellent explanation of the genome wide polygenic risk score (GPRS). Using data of 2.1 million SNPs as markers for ↑weight or ↓weight, we can predict with SOME accuracy what the #weight differential will be at middle age, comparing highest and lowest risk cohorts
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We're not just studying obesogenic genes but also those that protect against #obesity
This is a beautiful study, answering many of the questions we clinicians and our patients are asking:
🤔What happens if I stop the GLP1?
Here's one punch line that we all could've guessed:
⭐️Exercise mitigates #weight regain when anti #obesity #medicine is stopped⭐️
But there's a lot more to observe here:
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Here's the study method:
There's an "induction" phase 1 where #weightloss is caused by a low-calorie #diet over 8 weeks
Then everyone is randomized to 1 of these 4 groups
After 1 year, all of these interventions are stopped, and researchers just watch to see what happens to #weight
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Going back to this main figure, interesting things pop out:
👉We all slowly find our ways back to baseline weight regardless of #obesity treatment type
👉All groups (not just those with meds) rebounded to higher than what the weight was before the treatment phase, but greatest rebound was with liraglutide alone
👉Greatest additional weight loss was seen with combination lira+exercise
- drugs can cause false negative screens but not false positive screens
- you can probably just treat with mineralocorticoid antagonist instead of going through the diagnostic steps
- "Tirzepatide is a dual agonist"
👉It ↑GIP activity but GLP-1R agonism is less than that of endogenous GLP-1
- "Hypoglycemia is not a concern if you're not on insulin"
👉Risk of hypoglycemia ~1.4% vs. 0.2% in placebo in SURMOUNT-1
@alpanashuklamd et al examined the effect of macronutrient sequencing (carbs first vs carbs last) in ppl with diabetes, prediabetes, or gestational diabetes
Among those with prediabetes, we saw significant differences in glucose, insulin, ghrelin, and GLP-1 -- all favoring the "carbohydrates-last" food order
Always a pleasure to listen to @KevinH_PhD discuss his testing of hypotheses in contributors to #obesity 1/
Many people remember his 14-day study of ultra processed foods (UPF) vs unprocessed foods (n=20) that found energy intake was ~500 kcal/d LESS with unprocessed meals
Details you might not know:
- Groups were not matched for type of sugar
- No hint of a difference in insulin sensitivity between groups based on OGTT results
- Groups were not matched for beverage amount (and implication for speed of food intake)
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