Browse the evidence

Ghrelin levels, specifically the ratio of unacylated to acylated ghrelin, are altered in NAFLD patients, with decreased plasma unacylated/acylated ghrelin ratio and increased hypothalamic acylated ghrelin expression correlating with insulin resistance and NAFLD severity.

Research indicates that ghrelin signaling is disrupted in NAFLD, with specific changes in ghrelin ratios correlating with insulin resistance. While ghrelin antagonists like pegvisomant are being studied, they are not yet established treatments. Current clinical focus remains on GLP-1 agonists for managing NAFLD.

Bariatric surgery (BS) improves NAFLD outcomes by altering bile acid bioavailability, which activates the Fxr-Glp-1 axis, improves glucose homeostasis, and reestablishes normal ghrelin responses.

For obese patients with NAFLD, bariatric surgery is a viable treatment option that not only reduces weight but also improves liver health through hormonal changes. It reestablishes normal ghrelin responses and activates pathways that improve glucose homeostasis. If you are considering surgery, discuss how it might specifically benefit your liver health beyond weight loss.

GLP-1 receptor agonists protect endothelial function by reducing oxidative stress, inhibiting inflammation, and promoting nitric oxide (NO) production.

This node explains the biological mechanism: GLP-1 drugs help keep blood vessel linings healthy by reducing inflammation and oxidative stress, which prevents the buildup of plaque. This is a key reason why these drugs protect the heart.

GLP-1 receptor agonists reduce foam cell formation and promote anti-inflammatory M2 macrophage polarization, thereby stabilizing atherosclerotic plaques.

GLP-1 drugs help stabilize existing plaque in arteries by changing how immune cells (macrophages) behave. They encourage these cells to become 'anti-inflammatory' (M2 phenotype) and help remove excess cholesterol, which reduces the risk of plaque rupture and heart attack.

DPP-4 inhibitors, specifically sitagliptin, are significantly associated with an increased risk of biliary disorders, including gallbladder-related diseases and biliary malignant tumors.

If you are taking a DPP-4 inhibitor (like sitagliptin), be aware of symptoms like right-sided abdominal pain, nausea, or fever, which could indicate gallbladder issues. Discuss these risks with your doctor, especially if you have been on the medication for a long time.

Specific GLP-1 receptor agonists, semaglutide and liraglutide, are significantly associated with an increased risk of biliary disorders, including gallbladder-related diseases and biliary malignant tumors.

If you are taking Semaglutide or Liraglutide, watch for signs of gallbladder problems, such as pain in the upper right abdomen, nausea, or fever. These drugs can slow down your gallbladder, so report any such symptoms to your doctor promptly.

Genetic variants in GLP1R that increase weight loss efficacy are also associated with an increased risk of nausea and vomiting, suggesting a link between efficacy and side effects.

Research suggests that the same genetic factors that help you lose more weight with GLP-1 medications may also make you more prone to nausea and vomiting. This doesn't mean you must suffer, but it highlights why side effects vary so much between individuals. If you are struggling with severe side effects, it might be worth discussing with your doctor whether a different medication or dose adjustment could help, as your genetics might be driving both your response and your side effects.

GLP-1 receptor agonists (semaglutide 2.4 mg weekly, liraglutide 3.0 mg daily) cause modest bone mineral density (BMD) reduction and increase bone turnover markers (favoring resorption) in people living with obesity, mirroring the effects of calorie restriction.

If you are taking GLP-1 agonists like Wegovy or Saxenda for weight loss, expect a small decrease in bone density (around 2-3%) over a year, similar to losing weight through diet alone. This is not unique to the drug but to the weight loss itself. To protect your bones, prioritize resistance training and ensure you are getting enough calcium and Vitamin D. The benefit of weight loss generally outweighs this modest skeletal risk, but monitoring is advised.

An 8-week combined functional strength and nutrition education program does NOT significantly improve gait speed, health-related quality of life (HRQoL), or protein intake in older adults with pre-frailty and frailty, although exploratory analysis suggests potential trends.

Knowing you need more protein doesn't always mean you will eat more, especially if you live in a facility with limited menu choices. Focus on practical strategies like adding specific high-protein snacks or choosing protein-rich options from existing menus, rather than trying to completely change your diet overnight. Combine this with strength training for the best functional results.

Unintentional weight loss in type 2 diabetes is associated with a higher risk of all-cause mortality, whereas the association with intentional weight loss is unclear.

Unintentional weight loss in type 2 diabetes should be taken seriously as it may signal underlying health issues and is linked to higher mortality. The impact of intentional weight loss on mortality is less clear, so patients should focus on overall health management rather than just weight loss.

General obesity does not significantly increase the risk of incident cardiovascular disease (CVD) events in individuals with type 2 diabetes, although it does increase mortality risk.

For people with diabetes, managing weight is less about preventing heart attacks and more about preventing death from any cause. While obesity doesn't significantly increase CVD risk in diabetics, it does increase mortality risk, so weight management remains important.

Obstetrician-gynecologists generally perceive plant-based dietary patterns as safe and health-promoting for pregnant and lactating patients, yet a significant majority feel inadequately trained to provide nutrition counseling, leading to a discrepancy between positive attitudes and actual clinical recommendations.

For OB/GYNs: Recognize that your positive view of plant-based diets is supported by evidence, but your lack of training is the main barrier to recommending them. Seek out specific nutrition education or refer patients to dietitians to ensure safe implementation during pregnancy.

A healthy vegan diet increases basophil levels in the blood, whereas a healthy omnivorous diet decreases them, indicating diet-specific immune system modulation.

Switching to a healthy vegan diet may alter your immune profile by increasing basophil levels, a type of white blood cell. While this is a specific change, it highlights that plant-based diets actively modulate the immune system rather than just suppressing it.

A healthy vegan diet increases methylation at the ABCG1 locus (potentially elevating Type 2 Diabetes risk) while simultaneously increasing methylation at the PHOSPHO1 locus (potentially reducing Type 2 Diabetes risk), creating a complex and opposing effect on T2D biomarkers.

A healthy vegan diet has complex effects on Type 2 Diabetes biomarkers, increasing methylation at one locus (potentially raising risk) and another (potentially lowering risk). This suggests that the net effect on T2D risk is not straightforward and requires further investigation.

Transitioning from dulaglutide to tirzepatide improves glycemic control (increased time in range, decreased mean glucose) without increasing hypoglycemia in patients with type 2 diabetes undergoing hemodialysis.

For patients with type 2 diabetes on hemodialysis who are not achieving good blood sugar control on dulaglutide, switching to tirzepatide (2.5 mg weekly) can significantly improve blood sugar stability and reduce high blood sugar episodes without increasing the risk of dangerous low blood sugar. This switch should be considered when current therapy fails, keeping in mind that mild stomach issues may occur but are generally manageable.

Exercise interventions in T2D are mediated by molecular mechanisms including exerkines (e.g., GDF15, Irisin), b-cell function enhancement, and epigenetic changes.

Exercise works by triggering specific biological signals (like exerkines) that improve how your body handles sugar and protects your pancreas.

GLP-1 receptor agonists provide neuroprotective benefits, including potential improvement in cognitive function and reduction in neurodegenerative disease progression (Alzheimer's and Parkinson's).

GLP-1 RAs are being studied for their potential to protect the brain in Alzheimer's and Parkinson's disease. They may reduce inflammation and oxidative stress in the brain. While not yet a standard treatment for these conditions, the biological plausibility is strong, and patients with these diseases should discuss the potential benefits with their neurologist.

Indiscriminate use of Semaglutide for weight loss without medical supervision poses significant health risks, including gastrointestinal distress, hypoglycemia, and potential renal or pancreatic complications.

Do not use Semaglutide for weight loss without a doctor's prescription and monitoring. The risks, including severe stomach issues and low blood sugar, are significant when used indiscriminately. Sustainable weight loss requires lifestyle changes, not just medication.

GIP receptor antagonism promotes weight loss and protects against diet-induced obesity, potentially by enhancing leptin sensitivity in the hypothalamus and reducing lipid storage in adipose tissue.

Research indicates that blocking the GIP receptor (antagonism) can also lead to weight loss, possibly by improving how your body responds to leptin and reducing fat storage. This is an emerging area of treatment, with some drugs in clinical trials combining GIP antagonism with GLP-1 agonism for enhanced effects.

Resistance training does not significantly improve appendicular skeletal muscle mass (ASM) or appendicular skeletal muscle mass index (ASMI) in older adults with sarcopenia.

Do not expect resistance training to significantly increase your muscle mass or muscle mass index if you have sarcopenia. The benefits you feel (strength, balance) are likely due to your nervous system working better, not your muscles getting bigger. This is still a positive outcome for function, even if the scale or tape measure doesn't change much.

Higher starch intake is associated with lower levels of specific plasma proteins (adrenomedullin, IL1ra, FABP4, leptin, CCL20) that are themselves positively associated with increased CVD and mortality risk.

This finding suggests that moderate starch intake may help regulate inflammatory and adiposity-related proteins. However, since the association weakened after adjusting for BMI, maintaining a healthy weight is likely the primary driver of these benefits.

Spirulina supplementation does not significantly reduce waist circumference in the general adult population, though it may benefit obese individuals over 40.

Do not expect Spirulina to significantly reduce waist circumference for the general population. However, if you are obese and over 40, taking ≥2g/day may help. Focus on its proven benefits for overall weight and body fat reduction instead.

Off-label prescribing of semaglutide (Ozempic) for weight loss causes significant supply shortages for patients with type 2 diabetes who require the medication for its FDA-approved indication.

If you are considering Ozempic for weight loss, understand that it is a serious medication, not a cosmetic shortcut. It works by mimicking hormones that regulate hunger, but stopping it often leads to significant weight regain. Be aware that high demand for off-label use has caused shortages for people who need it for diabetes, so discuss ethical access and long-term sustainability with your doctor before starting.

Public health strategies targeting the obesogenic environment (e.g., SSB taxes, zoning, produce prescriptions) are necessary to support individual weight management efforts, as individual lifestyle advice is undermined by environmental factors.

Individual willpower is not enough in an environment designed to promote obesity. Support public health policies like sugar taxes, zoning for healthy food access, and produce prescription programs. These environmental changes make healthy choices easier and more affordable.