These studies collectively demonstrate that insulin resistance is independently associated with multiple serious health conditions including hypertension, cardiovascular disease, fatty liver disease, and accelerated cognitive decline in Alzheimer’s disease, reinforcing its role as a critical root cause of chronic disease progression. They link insulin resistance to hypertension, type 2 diabetes, cardiovascular disease, NAFLD and cognitive decline:

Study 1: Insulin Resistance and Hypertension in Brazilian Population

Title: Association of hypertension and insulin resistance in individuals free of diabetes in the ELSA-Brasil cohort

Published: June 10, 2023 URL: https://www.nature.com/articles/s41598-023-35298-y

Summary Findings: In a study of 4,717 Brazilian participants without diabetes or cardiovascular disease, researchers found that insulin resistance (measured by HOMA-IR) significantly increased the risk of developing both prehypertension and hypertension. The study followed participants for an average of 3.8 years and found that insulin resistance caused a 51% increased risk of developing prehypertension and a 150% increased risk of developing hypertension over time. The association remained significant even when controlling for body weight and obesity, indicating insulin resistance is an independent risk factor for elevated blood pressure.

Study 2: Insulin Resistance and Cardiovascular Disease in UK Biobank

Title: Insulin resistance assessed by estimated glucose disposal rate predicts cardiovascular disease in stages 0–3 of cardiovascular-kidney-metabolic syndrome: a UK biobank cohort study

Published: September 11, 2025 (Published online in Cardiovascular Diabetology) URL: https://cardiab.biomedcentral.com/articles/10.1186/s12933-025-02860-z

Summary Findings: This large UK study of 325,312 UK Biobank participants found that insulin resistance (measured by estimated glucose disposal rate/eGDR) was a powerful predictor of future cardiovascular disease events including coronary heart disease, stroke, atrial fibrillation, heart failure, and peripheral artery disease. Over a median follow-up of 13.57 years, 48,433 incident CVD cases were identified. Those with the highest insulin resistance had significantly higher rates of cardiovascular events. The study demonstrated that incorporating insulin resistance measurements significantly improved cardiovascular disease risk prediction beyond conventional risk equations.

Study 3: Insulin Resistance and Non-Alcoholic Fatty Liver Disease

Title: Correlation between liver fibrosis in non-alcoholic fatty liver disease and insulin resistance indicators: a cross-sectional study from NHANES 2017–2020

Published: January 14, 2025 (Published in Frontiers in Endocrinology) URL: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1514093/full

Summary Findings: This study of 904 NAFLD patients from the US National Health and Nutrition Examination Survey (NHANES 2017-2020) found that insulin resistance plays a crucial role in both the development of NAFLD and progression to liver fibrosis. Patients with liver fibrosis had significantly higher insulin resistance markers (TyG, METS-IR, HOMA-IR) compared to NAFLD patients without fibrosis. The triglyceride-glucose waist-to-height ratio (TyG-WHtR) was identified as an independent risk factor for liver fibrosis with an odds ratio of 2.69, confirming the strong association between insulin resistance and liver damage in NAFLD.

Study 4: Insulin Resistance and Cardiovascular Disease in Obesity

Title: Insulin resistance-related indices, genetic risk, and the risk of cardiovascular disease in individuals with preclinical or clinical obesity: a large prospective cohort study in the UK biobank

Published: October 25, 2025 (Published in Cardiovascular Diabetology) URL: https://cardiab.biomedcentral.com/articles/10.1186/s12933-025-02961-9

Summary Findings: This prospective UK study of 112,866 UK Biobank participants with obesity analysed insulin resistance-related indices (TyG index, TyG-BMI, TyG-WC, TyG-WHtR) and found strong associations with cardiovascular disease incidence, including total CVD, coronary artery disease, and stroke. The research demonstrated that insulin resistance mediates a substantial proportion (50.97%-66.72%) of the relationship between obesity and cardiovascular disease, showing a stronger influence than chronic inflammation. The findings confirm that insulin resistance is a critical mechanistic link between obesity and cardiovascular disease outcomes.

Study 5: Insulin Resistance and Cognitive Decline in Alzheimer’s Disease

Title: The Triglyceride-Glucose Index as Predictor of Cognitive Decline in Alzheimer’s Spectrum Disorders

Presented: June 23, 2025 at European Academy of Neurology Congress

URL: https://medicalxpress.com/news/2025-06-simple-insulin-resistance-cognitive-decline.html (Also published in Alzheimer’s & Dementia journal)

Summary Findings: In this Italian study of 315 non-diabetic patients (200 with confirmed Alzheimer’s disease), researchers found that insulin resistance measured by the triglyceride-glucose (TyG) index was a powerful predictor of rapid cognitive decline in early Alzheimer’s disease. Patients with mild cognitive impairment due to Alzheimer’s in the highest third of insulin resistance were four times more likely (hazard ratio 4.08) to experience rapid cognitive decline, losing more than 2.5 points per year on cognitive testing. This association was specific to Alzheimer’s disease and not observed in other neurodegenerative conditions, suggesting insulin resistance plays a disease-specific role in accelerating Alzheimer’s progression.

Study 6: IR and patients with essential hypertension

Title: Prevalence of insulin resistance and related risk factors for cardiovascular disease in patients with essential hypertension

https://pubmed.ncbi.nlm.nih.gov/18772854/

Conclusions: Approximately 50% of patients with essential hypertension, both treated and untreated, appear to be insulin resistant, and CVD risk factors are greatly accentuated in this subset of patients.