Browse the evidence

High fasting serum triglyceride levels (specifically 1.6–2.5 mmol/L) are a strong, independent risk factor for ischemic heart disease (IHD), even in individuals with high HDL cholesterol levels.

If you are a middle-aged or older man, your fasting triglyceride levels matter for your heart disease risk, even if your HDL (good cholesterol) is high. A level between 1.6 and 2.5 mmol/L is associated with a significantly higher risk of heart events. This suggests that managing triglycerides (often through diet, specifically reducing refined carbohydrates and alcohol) is crucial, regardless of your HDL status.

Dietary improvements in the US between 1999 and 2012 were not uniform across all demographic groups, with significant disparities persisting or worsening for non-Hispanic Black and Mexican American adults, as well as those with lower income levels.

Public health initiatives must target specific demographic groups with tailored interventions, as general dietary improvements have not reached all communities equally.

Experiencing weight discrimination is associated with a 60% increased risk of all-cause mortality, independent of BMI.

Recognize that social stress, including discrimination based on weight, has a measurable impact on longevity and health, independent of body weight. Reducing stigma and discrimination is a public health priority for improving mortality rates.

Weight stigma in healthcare settings leads to poorer quality of care, delayed medical attention, and worse health outcomes for patients with obesity.

If you have obesity, advocate for your health by seeking providers who focus on behaviors and metabolic markers rather than just weight. If you feel dismissed or stigmatized, seek a second opinion. Healthcare providers should be trained to recognize and mitigate their own biases to ensure equitable care.

The introduction of supermarkets into deprived communities has mixed effects on fruit and vegetable intake; while some studies show small improvements, robust quasi-experimental studies (e.g., in Glasgow) found little to no effect compared to control areas.

Moving to a neighborhood with a supermarket or expecting a new store to open near you is unlikely to significantly change your diet or help you lose weight. Studies show that simply adding stores does not reliably increase fruit and vegetable intake. Focus on your actual purchasing habits, budget, and food choices rather than relying on the presence of a specific store type.

Obesity triggers insulin resistance and type 2 diabetes through chronic low-grade inflammation driven by visceral adipose tissue expansion, which releases pro-inflammatory cytokines (TNF-α, IL-6) and activates Toll-like receptors (TLR4) to interfere with insulin signaling.

Focus on reducing visceral fat through sustainable lifestyle changes, as this tissue actively drives inflammation and insulin resistance. Strategies should aim to lower systemic inflammation, potentially through dietary patterns that reduce saturated fats and improve gut health, as these are linked to the inflammatory response described.

Mitochondrial dysfunction and ectopic lipid accumulation (triglycerides in muscle and liver) contribute to insulin resistance by reducing oxidative activity and ATP synthesis, leading to intramyocellular fat accumulation.

Improving mitochondrial health through regular physical activity, particularly aerobic exercise, can help clear ectopic fat from muscles and liver, thereby improving insulin sensitivity.

Activation of the estrogen-related receptor alpha (Errα) by PGC-1α drives the expression of oxidative phosphorylation (OXPHOS) genes in skeletal muscle, and this pathway is downregulated in diabetic muscle.

This research identifies Errα as a critical 'switch' for mitochondrial energy production in muscle, which is often stuck 'off' in diabetes. While no direct supplement is named, the findings suggest that therapies activating Errα (agonists) could improve insulin sensitivity and energy metabolism in diabetic muscle without affecting liver glucose production.

Errα and Gabpa form a double-positive-feedback loop with PGC-1α to drive robust expression of mitochondrial genes, and this loop is disrupted in diabetic muscle.

Diabetic muscle has a broken feedback loop between PGC-1α, Errα, and Gabpa. Restoring this loop, potentially via Errα agonists, could improve mitochondrial function.

High levels of foreign direct investment (FDI) and free-trade agreements with high-income countries drive increased consumption of unhealthy commodities (soft drinks, processed foods, tobacco, alcohol) in low- and middle-income countries (LMICs), independent of economic growth.

For policymakers in LMICs: Do not assume economic growth will automatically lead to better health or that unhealthy consumption is inevitable. Prioritize regulations on foreign direct investment and free-trade agreements. Restricting market access for multinational unhealthy commodity producers can prevent the rise of NCDs, even as the economy grows. Focus on domestic food system resilience rather than open markets for processed foods.

Prolonged exposure to television introduces Western beauty ideals (thinness, blonde hair, blue eyes) into previously isolated communities, leading adolescent girls to adopt negative eating behaviors and body dissatisfaction.

For communities or individuals newly exposed to global media, be aware that rapid adoption of thin-ideal body standards can lead to unhealthy dieting and purging. Proactively build media literacy to contextualize images as commercial constructs rather than health goals.

Obesity-induced infiltration of proinflammatory immune cells (macrophages and T cells) into skeletal muscle adipose depots (IMAT/PMAT) drives local inflammation, which impairs myocyte insulin signaling and contributes to systemic insulin resistance.

In obesity, fat storage around muscle fibers triggers an immune response that blocks insulin from working effectively in muscle cells. This is a biological inflammatory process, not just a dietary failure. Addressing the underlying inflammation through weight loss and metabolic health improvements can help restore insulin sensitivity.

Influx of free fatty acids (FFAs) and triglyceride-rich lipoproteins into skeletal muscle induces inflammation and insulin resistance via activation of TLR4, PKC, and JNK pathways.

High levels of circulating fats, especially saturated fats, can flood into muscle cells, causing inflammation and blocking insulin. Managing blood fat levels through diet (reducing saturated fats) and exercise can help prevent this lipid-induced insulin resistance.

Thiazolidinediones (PPAR-gamma agonists) improve insulin sensitivity and beta-cell function by enhancing adipocyte insulin sensitivity, inhibiting lipolysis, reducing plasma FFA, and redistributing fat away from visceral and hepatic depots to subcutaneous fat.

Thiazolidinediones (TZDs) are a class of diabetes medications that work by improving the function of fat cells. They help store fat in the right places (subcutaneous) rather than harmful places (liver, muscle), which reduces the toxic free fatty acids that cause insulin resistance. This improves how the body uses insulin and protects the pancreas.

Dysfunctional adipocytes in T2DM produce excessive insulin-resistant and inflammatory cytokines (e.g., resistin, TNF-alpha, IL-6, PAI-1) and secrete reduced amounts of insulin-sensitizing adipocytokines (e.g., adiponectin).

Fat tissue acts as an endocrine organ. In Type 2 Diabetes, fat cells become 'dysfunctional,' releasing too many inflammatory signals (like TNF-alpha and IL-6) that worsen insulin resistance, while releasing too few protective signals (like adiponectin) that help insulin work. This imbalance contributes to the progression of the disease.

Somatostatin infusion suppresses hyperglucagonemia and markedly reduces hyperglycemia in Type 1 Diabetic humans, even when insulin is reduced or discontinued.

In humans, suppressing glucagon with somatostatin lowers blood sugar even with low insulin. This supports the idea that targeting glucagon is a viable therapeutic strategy, though somatostatin's side effects limit its use.

Elevated plasma levels of specific ceramide subspecies (C18:0, C20:0, C24:1, C24:0) are associated with increased severity of insulin resistance in obese subjects with type 2 diabetes.

If you have type 2 diabetes, your body's fat metabolism produces specific lipids (ceramides) that interfere with how your cells respond to insulin. Higher levels of these lipids in your blood are linked to worse insulin resistance. While this paper doesn't prescribe a treatment, it highlights that managing lipid metabolism and inflammation is key to improving insulin sensitivity.

Plasma ceramide levels correlate with plasma TNF-α concentrations, suggesting a link between lipid accumulation and systemic inflammation in type 2 diabetes.

Inflammation and fat metabolism are connected in type 2 diabetes. High levels of certain fats (ceramides) in your blood are associated with higher levels of inflammatory markers (TNF-α). Reducing inflammation and managing fat metabolism may help address both issues.

Gut microbiota composition directly influences energy harvest, fat storage, and insulin sensitivity, with germ-free mice showing significantly less body fat and protection against diet-induced obesity compared to conventionally raised mice.

Your gut bacteria play a major role in how much energy you get from food and how likely you are to store it as fat. While you cannot directly 'eat' your microbiota, you can influence it through diet (fiber, prebiotics) and lifestyle (avoiding excessive antibiotics and fat), which may help manage weight and insulin sensitivity.

High-fat diets induce metabolic endotoxemia by increasing intestinal permeability and LPS translocation, leading to chronic low-grade inflammation and insulin resistance via the TLR-4 pathway.

High-fat meals can cause a temporary spike in inflammatory markers (endotoxemia) by allowing bacterial toxins (LPS) to enter your bloodstream. This is more pronounced with high-fat diets than high-carb diets. Eating fiber and fruits with meals may help mitigate this inflammatory response.

In older adults (over ~80 years), maintaining a gut microbiome that becomes increasingly unique (divergent from common profiles) and depletes core genera like Bacteroides is a marker of healthy ageing and predicts higher survival rates.

For older adults, the composition of your gut microbiome matters more than just its diversity. Research suggests that as you age, your microbiome naturally becomes more unique to you. This 'drift' away from common bacterial profiles (specifically a decrease in Bacteroides) is linked to better health and survival. Instead of focusing solely on boosting common bacteria, focus on a varied diet that supports a unique microbial ecosystem, as indicated by the production of specific amino acid derivatives in the blood.

Long-term calorie restriction (CR) prevents age-related large artery stiffening and endothelial dysfunction by reducing oxidative stress and inflammation.

To improve vascular health and slow aging, consider reducing your daily caloric intake by 25% while ensuring you get all necessary nutrients. This approach, validated by the CALERIE trial, has been shown to reduce cardiovascular risk factors and slow biological aging in nonobese adults.

Obesity-induced insulin resistance is mediated by an imbalance in pro- and anti-inflammatory adipokines, where increased pro-inflammatory adipokines (e.g., TNF-α, IL-6, leptin) and decreased anti-inflammatory adipokines (e.g., adiponectin) trigger inflammatory signaling cascades that suppress insulin receptor substrate (IRS) phosphorylation.

In obesity, fat tissue doesn't just store energy; it releases inflammatory signals (adipokines) that block insulin's action. This happens because the balance of these signals shifts towards inflammation (high TNF-alpha, IL-6, leptin) and away from protection (low adiponectin). Addressing insulin resistance requires understanding this inflammatory component, not just caloric intake.

Adipose tissue immune cell composition shifts in obesity from anti-inflammatory (M2 macrophages, Th2 T cells, Tregs) to pro-inflammatory (M1 macrophages, Th1 T cells, CD8+ T cells), driving local and systemic inflammation that contributes to insulin resistance.

Obesity changes the immune environment of fat tissue. Instead of anti-inflammatory cells that protect insulin sensitivity, pro-inflammatory immune cells (like M1 macrophages and Th1 T cells) take over, releasing chemicals that block insulin action.