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Inzulinska rezistencija je stanje poremećene sposobnosti odgovora na djelovanje inzulina. Najčešći osnovni uzrok je središnja pretilost, iako je primarna inzulinska rezistencija moguća i u osoba s normalnom težinom. Suvišno abdo-minalno masno tkivo otpušta povećane količine faktora tumorske nekroze α i slobodnih masnih kiselina, što izravno utječe na inzulinsko signaliziranje, smanjuje preuzimanje glukoze u mišićima, dovodi do pretjerane sinteze trigliceri-da i izaziva glukoneogenezu u jetri. Ostali čimbenici za koje se pretpostavlja da igraju ulogu u inzulinskoj rezistenciji su adiponektin (sniženje), leptin, IL-6 i neki drugi adipokini. Smatra se da je obična pretilost poligenog podrijetla uz utjecaj "pretilogene" okoline - povećan unos hrane i nedostatak tjelesne aktivnosti. Današnja visoka učestalost pretilosti mogla bi se objasniti evolucijskim pritiskom za odabir gena koji promiču pohranu masti za preživljenje u vrijeme gladovanja. Inzulinska rezistencija je prisutna zajedno sa središnjom pretilosti, hipertenzijom i dislipidemijom, koje se skupno označavaju kao metabolički sindrom. Ove pojavnosti predstavljaju snažne čimbenike rizika za šećernu bolest tipa 2 i kardiovaskularnu bolest., Insulin resistance is a state of impaired responsiveness to insulin action. The most common underlying cause is central obesity although primary insulin resistance in normal-weight individuals is also possible. Excess abdominal adipose tissue has been shown to release increased amounts of tumor necrosis factor α and free fatty acids, which directly affect insulin signaling, diminish glucose uptake in the muscle, drive exaggerated triglyceride synthesis and induce gluconeogenesis in the liver. Other factors presumed to play a role in insulin resistance are adiponectin (a decrease), leptin, IL-6 and some other adipokines. Common obesity is thought to be of polygenic origin with influence of "obesogenic" environment, i.e. increased food intake and the lack of physical activity. Today's high prevalence of obesity could be explained by evolutionary pressure for selection of genes promoting fat storage to survive in starvation. Insulin resistance frequently coexists with central obesity, hypertension and dyslipidemia, which have collectively been denoted as metabolic syndrome. These manifestations represent strong risk factors for diabetes mellitus type 2 and cardiovascular disease.