Browse the evidence

The depletion of Verrucomicrobia in obese-T2DM patients is associated with a loss of anti-inflammatory state and improved insulin sensitivity, potentially allowing the growth of pro-inflammatory Proteobacteria.

The study suggests that losing certain beneficial bacteria (like Verrucomicrobia) might contribute to insulin resistance. This highlights the importance of gut health in diabetes management, though it does not prescribe a specific probiotic or treatment.

Increased abundance of gram-negative bacteria (Dialister and Allisonella) in obese-T2DM patients is associated with elevated lipopolysaccharide (LPS) levels, which mediates inflammatory response and contributes to insulin resistance.

This finding links specific gut bacteria to inflammation and insulin resistance via LPS. It suggests that maintaining gut barrier integrity and avoiding unnecessary antibiotics may be important for metabolic health, although no specific intervention is tested here.

GIP receptor antagonists can promote weight loss in non-human primates and rodents, challenging the view that GIP promotes obesity.

Blocking GIP receptors (antagonism) has been shown to reduce weight gain in animal models, suggesting that endogenous GIP may play a role in promoting obesity. This supports the development of GIP antagonists for weight management.

Intermittent fasting preserves pancreatic beta-cell mass and improves glucose tolerance in obesity-induced diabetes by stimulating the autophagy-lysosome pathway.

Intermittent fasting may help preserve insulin-producing cells in obesity, but only if your cells can properly recycle waste (autophagy). If you have underlying cellular defects, fasting might stress your pancreas instead of helping it.

Intermittent fasting stimulates beta-cell regeneration markers (NEUROG3) in obesity-induced diabetes, but this effect is dependent on an intact autophagy-lysosome pathway.

Fasting may trigger regeneration signals in the pancreas during obesity, but this process is blocked if your cells cannot perform autophagy.

Insulin-like Growth Factor-I (IGF-I) administration ameliorates liver fibrosis and NASH by inducing cellular senescence in hepatic stellate cells (HSCs), thereby inactivating them and limiting fibrosis progression.

IGF-I shows promise in animal studies for reversing liver scarring (fibrosis) by putting the scar-forming cells into a state of 'senescence' where they stop working. While not yet a standard human treatment, it represents a potential future therapy for advanced liver disease.

Probiotics can improve gut barrier integrity and reduce metabolic endotoxemia (LPS translocation) in obese models, thereby lowering systemic inflammation.

A healthy gut lining helps prevent inflammation, which is linked to obesity. Probiotics may help strengthen this barrier, but the most effective way to support gut health is through a diet rich in fiber and fermented foods.

Dietary supplementation with Allium cepa (onion) extracts, particularly those rich in quercetin and organosulfur compounds, inhibits adipogenesis and promotes browning of white adipose tissue, leading to reduced fat accumulation and improved lipid profiles in preclinical models.

Incorporating onion peel extracts or quercetin-rich onion preparations into your diet may support metabolic health by inhibiting the formation of new fat cells and promoting the browning of white fat. While not a magic bullet for weight loss, it serves as a supportive dietary strategy for managing lipid profiles and insulin sensitivity, particularly when combined with a balanced diet.

Sotagliflozin is a dual SGLT1/SGLT2 inhibitor that reduces postprandial glycemia by blocking intestinal glucose absorption and renal glucose reabsorption.

Sotagliflozin is a newer diabetes medication that works in two places: your intestines and your kidneys. It helps lower blood sugar spikes after meals by preventing sugar absorption in the gut and removing sugar through urine. It is still being studied for long-term safety.

Short-term manipulation of energy availability (≤5 days) triggers acute endocrine and metabolic dysregulations, but the long-term physiological effects of chronic LEA remain causally unproven due to a lack of long-duration prospective studies.

While short-term low energy availability clearly disrupts hormones, we lack long-term prospective data to definitively predict the chronic health outcomes of sustained LEA in humans.

Insulin resistance is a key feature of PCOS, but routine clinical measurement of insulin resistance is not recommended due to the inaccuracy of currently available measures.

While insulin resistance is common in PCOS, current clinical tests for it are not accurate enough to guide individual treatment decisions. Focus on lifestyle changes (diet, exercise) which improve insulin sensitivity, rather than seeking specific insulin blood tests.

Activation of PPARγ (via agonists like TZDs or endogenous upregulation) improves insulin resistance and metabolic homeostasis by enhancing adipose tissue expandability, reducing ectopic lipid accumulation, and promoting browning, rather than solely by reducing fat mass.

Focus on improving the health and capacity of your fat tissue rather than just trying to lose weight. Strategies that support healthy adipose tissue function (like those mediated by PPARs, e.g., through specific medications or lifestyle factors that promote adipogenesis and browning) can improve insulin sensitivity even if body weight remains stable or increases slightly. The key is preventing fat from accumulating in organs like the liver and muscles.

PPARβ/δ activation reduces systemic inflammation and promotes fatty acid oxidation in skeletal muscle and brown adipose tissue, offering potential therapeutic benefits for obesity and insulin resistance.

PPARβ/δ activation shows promise for reducing inflammation and improving metabolism in muscle and fat, though it is still under clinical study.

Soy isoflavones can induce goitrogenic effects in individuals with pre-existing hypothyroidism or iodine deficiency, potentially advancing subclinical hypothyroidism to overt hypothyroidism.

If you have hypothyroidism, consult your doctor before consuming large amounts of soy isoflavones, as they may worsen thyroid function in some cases, especially if iodine intake is adequate.

Gut-derived hormones (CCK, GLP-1, PYY) released by enteroendocrine cells in response to nutrient ingestion activate vagal afferents and hypothalamic centers to inhibit food intake and increase energy expenditure, thereby regulating energy homeostasis.

Your body has a sophisticated biological system that regulates hunger and energy using signals from your gut. When this system is disrupted (as seen in obesity), simple willpower often fails because the biological 'stop' signals (like GLP-1 and CCK) are not functioning correctly. Effective treatments often target these specific pathways (e.g., GLP-1 agonists) to restore the body's natural ability to regulate intake and expenditure.

Repeated administration of CCK leads to desensitization and tolerance, explaining why CCK-derivatives have failed as effective long-term weight-loss treatments.

Early attempts to use CCK mimics for weight loss failed because the body builds tolerance to them. This highlights that simply flooding the system with one satiety signal is not a sustainable long-term strategy without addressing the underlying regulatory mechanisms.

Exercise-induced myokines (exerkines) such as SDF1, irisin, and SPARC counteract muscle wasting in diseases like cancer cachexia, COPD, and aging by modulating protein synthesis and degradation pathways.

If you are dealing with muscle loss due to illness or age, regular physical activity is a key treatment. It triggers your muscles to release protective proteins (myokines) that help stop muscle breakdown. You do not need to be an athlete; even moderate aerobic or resistance exercise can help restore these protective factors.

Metformin administration is associated with a reduced incidence of multiple age-related diseases and all-cause mortality in both diabetic and non-diabetic populations.

If you are taking metformin for diabetes, you may already be benefiting from reduced risks of age-related conditions. For non-diabetics considering metformin for longevity, the evidence is promising but not yet definitive (TAME trial pending). Discuss with your doctor, especially regarding kidney function and potential side effects like GI distress, which can often be managed with dosing strategies.

Metformin treatment improves outcomes in osteoarthritis (OA) by reducing inflammation, protecting articular cartilage via the AMPK pathway, and reducing body weight.

For those with osteoarthritis, especially if overweight, metformin (if prescribed for diabetes) may offer additional joint protection and pain relief. This is likely due to its anti-inflammatory properties and weight loss effects. Consult your doctor about whether existing metformin therapy is contributing to joint health.

Metformin use is associated with a reduced risk of various cancers, including breast, colorectal, and pancreatic cancer, though effects on pancreatic cancer prognosis are mixed.

If you have diabetes and take metformin, you may have a lower risk of developing certain cancers like breast and colorectal cancer. However, it is not a cancer treatment itself. Do not stop taking metformin to 'prevent' cancer without consulting your doctor, as the benefits for diabetes management are primary.

Higher circulating levels of phospholipid metabolites, specifically choline, glycerophosphoethanolamine, and glycerophosphorylcholine (GPC), are associated with an insulin-sensitive phenotype in obese individuals, distinguishing them from obese insulin-resistant individuals.

This research suggests that for obese individuals, metabolic health (specifically insulin sensitivity) can be distinguished by blood levels of choline and related phospholipids. Higher levels of these metabolites are linked to a protective, insulin-sensitive state. This implies that metabolic health is not uniform across all obese individuals and may be assessed through specific biomarkers rather than weight alone.

Increased levels of specific fatty acid metabolites (3-hydroxylaurate, 3-hydroxyoctanoate, 3-hydroxydecanoate, 3-hydroxymyristate) and decreased levels of 1,5-anhydroglucitol (1,5-AG) and dimethylarginine (ADMA+SDMA) are associated with disease progression from insulin resistance to Type 2 Diabetes.

For individuals with obesity and insulin resistance, monitoring specific fatty acid metabolites and 1,5-AG levels may provide early warning signs of progression to Type 2 Diabetes. Decreasing 1,5-AG and increasing certain hydroxy-fatty acids are associated with this progression, suggesting these could be valuable markers for early intervention.

Administration of Meteorin-like protein (METRNL) attenuates lipid-induced inflammation and insulin resistance in skeletal muscle by activating AMPK and PPARδ signaling pathways, leading to increased fatty acid oxidation and reduced pro-inflammatory cytokine expression.

This research suggests that the metabolic benefits of exercise are partly driven by specific proteins (like METRNL) released by muscles, which directly improve insulin sensitivity and reduce inflammation. While this specific protein is not yet a commercial supplement, the finding supports the importance of resistance training and physical activity for managing metabolic health, independent of weight loss or calorie counting.

SIRT3 suppresses lipogenesis in hepatocytes by downregulating the expression of Stearoyl-CoA desaturase 1 (SCD1).

Reducing the intake of saturated fats and maintaining metabolic health may help regulate SCD1, a key enzyme in fat synthesis. This complements the autophagy mechanism by reducing the load of new fat entering the liver.