Hormonal
Hyperinsulinemia promotes obesity by inhibiting lipolysis and promoting lipogenesis at insulin concentrations lower than those required to inhibit gluconeogenesis.
Focus on keeping your fasting insulin low to prevent fat gain. Even modest increases in insulin (e.g., from doubling your baseline) can shut down fat burning (lipolysis) and start fat storage (lipogenesis) before your blood sugar regulation is even affected. This suggests that frequent snacking or high-carb meals, which keep insulin elevated, are more likely to cause weight gain than occasional high-sugar meals that spike glucose but clear quickly.
Doubling fasting insulin levels suffices to inhibit lipolysis by approx. 50% and to promote lipogenesis... For half-maximal inhibition of gluconeogenesis, insulin concentrations must rise to approx. 160 pmol/l... In order to stimulate glucose uptake to half maximum, insulin levels must rise to even higher levels, approx. ten times the fasting insulin concentrations
Why this rating
Supported by human infusion studies, genetic studies, and Mendelian randomization.
Source
Insulin: too much of a good thing is bad
Hubert Kolb et al. · BMC Medicine · 2020
DOI 10.1186/s12916-020-01688-6
More from this paper
- Chronically elevated insulin levels (hyperinsulinemia) directly cause obesity, cardiovascular disease, and reduced lifespan through selective signaling pathways that remain active despite insulin resistance.Good
- Chronic hyperinsulinemia reduces lifespan and healthspan by suppressing autophagy and antioxidant defenses (Nrf2) while promoting cellular senescence and cardiovascular damage.Moderate
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →