Researchers Find Potential Tool For Assessing Insulin Resistance

The landscape of cardiometabolic care is shifting from reactive treatment to proactive risk stratification, and a new longitudinal analysis of the UK Biobank suggests that pharmacists may have a more effective way to predict how their patients will progress from health to chronic disease.¹

“Measuring insulin resistance in clinical setttings remains challenging. The hyperinsulinemic-euglycemic clamp, though considered as the gold standard for insulin resistance assessment, is invasive, time-consuming, and impractical for large-scale clinical application,” the study authors said.

This study published in Nutrition and Metabolism, which tracked over 350,000 patients, found that surrogate markers for insulin resistance can effectively map the trajectory of cardiometabolic multimorbidity, defined as the coexistence of at least 2 conditions such as type 2 diabetes, ischemic heart disease, and stroke. At the heart of this research is the estimated glucose disposal rate (eGDR), a calculation that outperformed 6 other common metrics in predicting which patients would transition from a disease-free state to their first diagnosis and, ultimately, to multiple metabolic failures.

For pharmacists, the importance of eGDR lies in its practical application, as it utilizes readily available clinical parameters that include waist circumference, hypertension status, and glycated hemoglobin (hemoglobin A_1c). Although the hyperinsulinemic-euglycemic clamp remains the gold standard for measuring insulin resistance, its invasive and time-consuming nature makes it impractical for routine clinical use. The UK Biobank findings underscore that eGDR provides a robust alternative for identifying high-risk individuals before they reach the point of irreversible organ damage, particularly in those with type 2 diabetes-related trajectories.

The necessity of such early detection is further emphasized by research into the "pre-prediabetic" state, which reveals that insulin resistance often lurks beneath the surface of seemingly healthy lab results. In a community-based study of nonobese patients with normal fasting plasma glucose and A_1c levels, approximately 1 in 4 individuals were found to be insulin resistant.²

These "pre-prediabetic" patients demonstrated significant indicators of cardiometabolic risk, including increased 1-hour plasma glucose levels exceeding 155 mg/dL during a glucose tolerance test and early-stage beta-cell dysfunction. Perhaps most concerning for long-term health is the presence of accelerated atherogenesis in these individuals. This study, published in The Journal of Clinical Endocrinology and Metabolism, noted a significantly higher prevalence and burden of carotid plaque in insulin-resistant patients even when their body mass index and glycemic markers appeared normal.

This metabolic dysfunction is driven by complex molecular pathways that pharmacists are uniquely positioned to address through medication management. Insulin resistance is essentially an impaired response to physiological levels of insulin, disrupting the phosphatidylinositol 3-kinase pathway responsible for glucose uptake and lipid metabolism and often leaving the mitogen-activated protein kinase pathway, which regulates cell growth and proliferation, relatively untouched.³

This selective insulin resistance contributes to a proinflammatory and prothrombotic environment, leading to endothelial dysfunction and impaired vasodilation. When the vascular endothelium becomes insulin resistant, the delivery of both insulin and glucose to peripheral tissues is hindered, creating a self-reinforcing cycle of metabolic and cardiovascular decline.

Managing this trajectory requires a multifaceted pharmacological approach beyond simple glycemic control. Although metformin remains a foundational therapy by suppressing hepatic glucose production, newer classes of medications offer direct cardiometabolic benefits. Thiazolidinediones target the pathophysiology of insulin resistance by activating PPARγ, though they require careful monitoring for adverse effects such as water retention. More recently, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as vital tools for cardiometabolic protection. GLP-1 agonists improve cardiovascular risk factors such as hypertension and dyslipidemia, and SGLT2 inhibitors reduce exogenous insulin requirements and promote weight loss.

By integrating tools like eGDR into clinical assessments, pharmacists can better identify patients who are on a high-risk trajectory toward multimorbidity. Understanding that insulin resistance and vascular damage can begin decades before an official diabetes diagnosis allows for earlier lifestyle and pharmacological adjustments that may prevent the transition from a single morbidity to the more lethal state of cardiometabolic multimorbidity.¹

“Our approach not only confirms the established associations but significantly extends them, providing a more nuanced understanding of disease progression and highlighting critical stages where intervention may be most effective,” the study authors said.

As the front line of medication management, pharmacists are essential in translating these insights from the bench to the bedside, ensuring that patients receive personalized therapy that addresses the fundamental pathophysiology of insulin resistance before it progresses to untreatable stages.³

READ MORE: Insulin Management Resource Center

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REFERENCES

1. Han Y, Wu J, Yao M, et al. Assessment of insulin resistance indexes with longitudinal trajectories of cardiometabolic multimorbidity: insights from the UK Biobank. Nutr Metab (Lond). Published online March 14, 2026. doi:10.1186/s12986-026-01098-0

2. Armato J, DeFronzo RA, Abdul-Ghani M, Ruby R. Pre-Prediabetes: Insulin Resistance Is Associated With Cardiometabolic Risk in Nonobese Patients (STOP DIABETES). J Clin Endocrinol Metab. 2025;110(5):e1481-e1487. doi:10.1210/clinem/dgae540

3. Kim J. Insulin resistance and cardiometabolic syndrome. Cardiometab Syndr J. 2021 Mar;1(1):24-45. Published online Feb 19, 2021. doi:https://doi.org/10.51789/cmsj.2021.1.e9