Browse the evidence

Glucagon receptor blockade or suppression prevents the catabolic consequences of insulin deficiency (hyperglycemia, ketoacidosis) in animal models.

In animal models, preventing glucagon from acting stops diabetes even without insulin. This suggests that therapies blocking glucagon could potentially manage blood sugar without the need for high-dose insulin, reducing side effects.

Pro-inflammatory adipokines such as TNF-α and IL-6 induce insulin resistance by activating kinases (JNK, IKKβ) that phosphorylate IRS1/2 on serine residues, thereby inhibiting tyrosine phosphorylation and downstream insulin signaling.

Insulin resistance isn't just about 'too much insulin'; it's about the signal being blocked. Inflammation from fat tissue activates specific enzymes (JNK, IKKβ) that physically block the insulin receptor's ability to work by modifying key proteins (IRS) at the wrong spot (serine instead of tyrosine).

Sibutramine was withdrawn from the market because long-term use increases the risk of non-fatal myocardial infarction and stroke in patients with cardiovascular risk factors.

Sibutramine is no longer available because it increases the risk of heart attack and stroke in people with existing heart conditions. It was withdrawn from the market in 2010.

Autoimmune thyroid disease (AITD) is significantly more prevalent in patients with Type 1 Diabetes (T1D) than in the general population, sharing common genetic susceptibility factors.

If you have Type 1 Diabetes, you are at a much higher risk for autoimmune thyroid disease (17-30% prevalence). Regular screening for thyroid function (TSH) and antibodies (TPO) is recommended, even if you feel healthy, to prevent complications and ensure optimal diabetes management.

Long-term DHEA or low-dose testosterone replacement in elderly people with low androgen levels does not produce clinically relevant improvements in body composition, physical performance, insulin sensitivity, or quality of life.

If you are an older adult with low hormone levels, taking DHEA or testosterone patches for 2 years will not make you stronger, fitter, or metabolically healthier, nor will it improve your quality of life. While testosterone might add a tiny amount of fat-free mass in men, it does not translate to better muscle strength or function. The treatment is safe regarding prostate health in this context, but it does not deliver the 'anti-aging' benefits often marketed.

The combination of oral estrogen use with prothrombotic mutations (Factor V Leiden or Prothrombin G20210A) or obesity significantly enhances the risk of venous thromboembolism.

If you have a known blood clotting mutation (like Factor V Leiden) or are overweight/obese, taking oral estrogen significantly increases your risk of blood clots (up to 8 times higher for mutations). However, using transdermal estrogen (patches/gels) does not appear to add extra risk for these high-risk groups, making it a safer choice to discuss with your doctor.

Glucocorticoid administration induces skeletal muscle atrophy primarily by stimulating the ubiquitin-proteasome system (UPS) via FOXO transcription factors and downregulating IGF-I signaling, while simultaneously inhibiting protein synthesis through mTOR repression.

If you are prescribed glucocorticoids, muscle loss is driven by active molecular switches (FOXO, mTOR) rather than just inactivity. While you cannot stop the medication, being aware that this is a specific biological response helps in seeking targeted counter-measures (like specific nutritional or pharmacological interventions discussed in the paper) rather than assuming the loss is inevitable or purely due to lack of exercise.

Hepatic insulin resistance, characterized by failure to suppress hepatic glucose production (gluconeogenesis and glycogenolysis), is a major feature of type 2 diabetes pathophysiology.

Managing fasting blood glucose often requires addressing hepatic glucose output, which can be influenced by weight loss and specific medications that target liver insulin sensitivity.

Levothyroxine therapy does not improve thyroid-related symptoms or quality of life in older adults (≥65 years) with subclinical hypothyroidism.

If you are over 65 and have subclinical hypothyroidism (high TSH but normal T4), taking levothyroxine is unlikely to make you feel less tired or improve your quality of life. While the medication will lower your TSH levels, it does not appear to provide clinical benefits for symptoms in this age group.

Insulin is the primary hormonal inhibitor of lipolysis, acting by activating phosphodiesterase-3B to lower cAMP levels and preventing hormone-sensitive lipase (HSL) activation.

Insulin is the body's main signal to stop breaking down fat. High insulin levels (e.g., from high carbohydrate intake) will inhibit lipolysis. To maximize fat mobilization, managing insulin through dietary composition and timing is important, but it is just one part of the complex regulation involving catecholamines and other factors.

Glucocorticoids (corticosteroids) act as a primary synchronizing signal from the central SCN to peripheral clocks, particularly in the liver, regulating up to 60% of the hepatic transcriptome.

Cortisol rhythms help synchronize your liver's metabolism to the day. Disrupting this rhythm (e.g., through stress or irregular sleep) may impair liver function and detoxification pathways.

PPARgamma mutations (loss-of-function) cause familial partial lipodystrophy type 3 (FPLD3), characterized by lack of subcutaneous fat in extremities and metabolic complications like type 2 diabetes.

Fat distribution is partly genetic. If you have a rare condition like FPLD3, your fat distribution and metabolic risks are driven by specific genetic mutations.

Therapeutic CPAP does not significantly improve glycaemic control (HbA1c) or insulin resistance (measured by euglycaemic clamp and HOMA) in men with established type 2 diabetes and obstructive sleep apnoea.

If you have type 2 diabetes and sleep apnoea, using CPAP will help you feel less sleepy and improve your quality of life, but it will not lower your blood sugar or fix insulin resistance on its own. You still need to manage your diabetes with diet, medication, or other treatments specifically designed for metabolic control.

The intrinsic human circadian period averages 24.1 to 24.2 hours, not 25 hours as previously estimated in older studies.

Your body clock is naturally slightly longer than 24 hours. To stay aligned with the day, you need to manage light exposure, especially in the evening, to prevent your clock from drifting later.

Mutations in the leptin-melanocortin pathway genes (LEP, LEPR, POMC, PCSK1, MC4R) cause severe, early-onset obesity through hyperphagia and altered energy expenditure.

If you have severe early-onset obesity, ask your doctor about genetic testing. For some, specific medications (like leptin therapy) can be highly effective because they target the root biological cause.

GLP-2 (specifically the analogue teduglutide) promotes intestinal mucosal growth and nutrient absorption, making it an effective treatment for short bowel syndrome (SBS).

For patients with short bowel syndrome who rely on intravenous nutrition, teduglutide (a GLP-2 analogue) is an approved daily injection that helps the intestine grow and absorb more nutrients. This can reduce the need for intravenous feeding. It is specifically designed to resist breakdown in the body, making it effective for chronic use.

Hormonal markers, such as the testosterone/cortisol ratio, are not reliable for diagnosing Overtraining Syndrome because they reflect acute physiological strain rather than the syndrome itself, and no single hormonal test is generally accepted.

Do not rely on a single blood test, such as the testosterone/cortisol ratio, to diagnose overtraining. These markers reflect acute stress and vary widely. A comprehensive assessment including performance trends, mood, and exclusion of other health issues is required.

Advanced maternal age (≥35 years) is a strong, non-modifiable risk factor for GDM, with risk increasing linearly with age.

If you are over 35, be aware your risk for GDM is higher. Prioritize the lifestyle interventions (diet and exercise) mentioned earlier, as they are even more critical for this age group.

Nocturnal supplemental oxygen does not reduce blood pressure in patients with obstructive sleep apnea, despite effectively reducing nocturnal hypoxemia.

If you have sleep apnea, using supplemental oxygen at night will not lower your blood pressure, even if it improves your oxygen levels. CPAP is required to reduce blood pressure. Oxygen might be used for other reasons, but it is not a substitute for CPAP for cardiovascular risk reduction.

Skeletal muscle-specific deficiency in mitochondrial OxPhos (via Crif1 knockout) activates the UPRmt, leading to elevated GDF15 secretion, which protects against obesity and insulin resistance.

Maintaining muscle mitochondrial health may naturally upregulate GDF15, a hormone that helps regulate body weight and blood sugar.

Prostaglandin D2 (PGD2) is a major sleep-promoting eicosanoid produced by leptomeninges and choroid plexus that stimulates sleep by eliciting adenosine release from arachnoid cells, which then acts on the ventrolateral preoptic area (VLPO).

PGD2, produced in the membranes surrounding the brain, promotes sleep by triggering the release of adenosine, which then acts on sleep-active neurons. This highlights a complex interaction between brain structures and biochemical signals in regulating sleep.

Tirzepatide treatment does not increase the risk of major adverse cardiovascular events (MACE-4) in patients with type 2 diabetes compared to control groups.

If you have type 2 diabetes, taking tirzepatide once a week does not increase your risk of heart attacks, strokes, or cardiovascular death compared to other standard treatments. This holds true for patients with both low and high existing heart risk, providing a safe option for cardiovascular protection while managing blood sugar.

High-dose vitamin D supplementation (4000-10,000 IU/day) does not improve bone health and is associated with a significant decrease in volumetric bone mineral density (BMD) at the radius and tibia compared to a low dose (400 IU/day).

If you are a healthy adult over 55 with normal vitamin D levels, taking high-dose vitamin D (4000-10,000 IU daily) will not strengthen your bones and may actually weaken them over time. Stick to standard recommended doses (around 400-800 IU) unless you have a diagnosed deficiency, as high doses can disrupt the hormones that regulate bone density.

Hormone replacement therapy (HRT) with estrogen plus progestin in postmenopausal women increases the risk of coronary heart disease, stroke, and pulmonary embolism without improving cardiovascular outcomes.

If you are a postmenopausal woman considering hormone replacement therapy, understand that current evidence suggests it does not prevent heart disease and may actually increase the risk of heart attacks, strokes, and blood clots. It should only be used to manage severe menopausal symptoms for the shortest duration possible, after a thorough discussion of risks with your doctor.