insulin resistance

Overview

Insulin resistance is a biological process in which target tissues such as skeletal muscle, liver, adipose tissue, and, in some contexts, the brain respond less effectively to insulin. As a result, normal insulin signaling is impaired, glucose uptake and metabolic regulation are reduced, and compensatory hyperinsulinemia may develop. It is a central feature of type 2 diabetes and is also implicated in gestational diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, obesity, polycystic ovary syndrome, cardiovascular risk, and several other metabolic and inflammatory disorders.

At the molecular level, insulin resistance is commonly associated with altered insulin receptor signaling and downstream pathways such as IRS-1/PI3K/AKT, PPARγ-driven signaling, and related metabolic regulators including PTP1B, mTORC1, and FOXO1. It is also linked to adiposity, ectopic fat accumulation, oxidative stress, inflammation, mitochondrial dysfunction, and changes in hepatokine and adipokine production. Recent studies have continued to frame insulin resistance as both a mechanistic driver and a therapeutic target across metabolic disease, pregnancy complications, pulmonary impairment, cognitive decline, and tissue repair.

Focus of Latest Publications

Recent publications have focused on insulin resistance as a measurable metabolic feature across obesity, diabetes, and related cardiometabolic conditions, using it both as an outcome and as a stratification variable. In obese men, a randomized controlled trial examined whether 12 weeks of fisetin supplementation could enhance the effects of interval resistance-aerobic training on Maresin-1, inflammatory markers, and insulin resistance. In another obesity-focused study, triglyceride-glucose-based indices and homeostatic model assessment for insulin resistance were evaluated in US adults to determine whether these surrogate markers could distinguish clinical obesity from preclinical obesity and help with risk stratification.

Several studies assessed insulin resistance in relation to disease mechanisms and treatment response. In mice exposed to chronic intermittent hypoxia, photobiomodulation was investigated as a non-invasive therapy to prevent intermittent hypoxia-induced insulin resistance by preserving insulin signaling in adipose tissue and reducing hepatic oxidative stress. In type 2 diabetes, estimated glucose disposal rate was used as an insulin resistance measure in the ADVANCE study to examine associations with vascular events, death, and possible modification of glucose- and blood pressure-lowering treatment effects. A post hoc analysis of the LAMP trial also evaluated whether baseline insulin resistance influenced the effect of liraglutide on recurrent stroke.

Other recent work linked insulin resistance to broader clinical phenotypes and disease progression. One study explored insulin resistance as a mediator of suicide risk in bipolar disorder, alongside immune-metabolic markers, white matter integrity, and suicidality. Another examined insulin resistance surrogates in relation to preserved ratio impaired spirometry in US adults, reflecting interest in pulmonary impairment and Cardiometabolic comorbidity. In the CALERIE-2 post hoc analysis, investigators assessed long-term metabolic and hormonal consequences of sustained weight loss versus weight regain, with attention to insulin resistance and type 2 diabetes risk.

Mechanistic and modeling studies also continued to frame insulin resistance as a central driver of metabolic deterioration. A mathematical modeling study of obesity-diabetes progression in Southwest Native Americans treated hyperinsulinemia as compensatory for insulin resistance and showed that insulin resistance, together with chronic calcium stress, could accelerate beta-cell failure and diabetes progression. Overall, these publications emphasize insulin resistance as a common biological process connecting obesity, oxidative stress, pulmonary and neuropsychiatric phenotypes, and progression toward overt diabetes, while also testing interventions such as exercise, fisetin, photobiomodulation, and liraglutide.

Key Publications

Jun 12‑weeks fisetin supplementation and interval resistance with aerobic training: changes in Maresin‑1 and inflammatory markers in men with obesity: a randomized controlled trial. (Journal of the International Society of Sports Nutrition, 2026, PMID 42218768): "This study examined whether fisetin supplementation augments the effects of concurrent interval resistance-aerobic training on Maresin‐1, pro‐inflammatory markers, and insulin resistance in obese men."
Jun Photobiomodulation Alleviates Insulin Resistance Induced by Intermittent Hypoxia, Through Preservation of Adipose Tissue Insulin Signaling and Reduction of Hepatic Oxidative Stress in Mice. (Comprehensive Physiology, 2026, PMID 42216497): "We hypothesize that photobiomodulation (PBM), a non-invasive low-level laser therapy, prevents IH-induced insulin resistance (IR), by preserving insulin signalization and reducing oxidative stress in insulin-sensitive organs."
Jun Insulin Resistance as a Mediator of Suicide Risk in Bipolar Disorder: A Neurobiological and Imaging Study. (Bipolar disorders, 2026, PMID 42212480): "These conditions are also linked to systemic inflammation and white matter (WM) alterations, which may underlie suicidal behaviors."
May Triglyceride-glucose indices distinguish clinical from preclinical obesity in US adults: A cross-sectional study. (Medicine, 2026, PMID 42175452): "The triglyceride-glucose (TyG) and TyG-related indices are surrogate markers of insulin resistance and may reflect differences across obesity phenotypes."
May Liraglutide and Recurrent Stroke by Baseline Insulin Resistance: A Post Hoc Analysis of the LAMP Trial. (Stroke, 2026, PMID 42145088): "Although body mass index does not seem to modify these effects, whether insulin resistance influences treatment efficacy remains unclear."
Jun Insulin resistance surrogates and their associations with preserved ratio impaired spirometry in United States adults. (Respiratory medicine, 2026, PMID 42061475): "Insulin resistance (IR) has been increasingly implicated in pulmonary impairment, yet its association with PRISm remains unclear."
May Weight Regain Reverses Caloric Restriction-Induced Benefits on the Insulin-IGF-1 Nutrient-Sensing Pathway: Post Hoc Analysis From the CALERIE-2 Randomized Controlled Trial. (Diabetes care, 2026, PMID 41838032): "To investigate the long-term metabolic and hormonal consequences of sustained weight loss versus weight regain after 1 year of caloric restriction (CR), with attention to insulin resistance and type 2 diabetes risk."
May Estimated Glucose Disposal Rate and Risk of Vascular Events and Death in Type 2 Diabetes in the ADVANCE Study. (Diabetes, obesity & metabolism, 2026, PMID 41804187): "To determine the association of insulin resistance, assessed using the estimated glucose disposal rate (eGDR), and the risk of adverse clinical outcomes, and determine any effect modification on the efficacy of glucose- and blood pressure (BP)-lowering treatments."
May Is high insulin protective or detrimental? Mathematical modeling reveals the base of the iceberg. (American journal of physiology. Endocrinology and metabolism, 2026, PMID 41800787): "The model captured heterogeneous trajectories of glucose, insulin, insulin sensitivity, and beta-cell function, under the assumption that hyperinsulinemia reflects compensation for insulin resistance rather than a primary defect."