Joint association of estimated glucose disposal rate and body mass index with new-onset stroke

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Joint association of estimated glucose disposal rate and body mass index with new-onset stroke

Ting Yu¹Da-Ming Shao²Tian Lv³Yu-Jun Xiong^4*

• ¹Department of Neurosurgery, Tiantai People's Hospital, Zhejiang, China
• ²Department of Rheumatology, The University of Chicago Medical Center, Chicago, IL, United States
• ³Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, China
• ⁴Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

Background: Stroke is a major global health concern, and understanding its modifiable risk factors is critical for prevention. Body mass index (BMI) and estimated glucose disposal rate (eGDR), indicators of adiposity and insulin sensitivity, respectively, are independently associated with stroke risk. However, the combined effects of these factors remain underexplored.

Methods: This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS), including 7,212 adults aged over 45 years. Cox proportional hazards models assessed the independent and joint associations of BMI and eGDR with new-onset stroke. Mediation analysis evaluated BMI’s role in the eGDR-stroke relationship. Subgroup analyses by age, sex, and BMI categories were conducted.

Results: Over a 7-year follow-up, 587 participants (8.14%) experienced new-onset stroke. Higher BMI was positively associated with stroke incidence, while lower eGDR was linked to increased stroke risk. Participants with both obesity (BMI over 28 kg/m²) and lower eGDR faced the highest stroke risk (HR: 2.63; 95% CI: 1.78–3.89). Mediation analysis revealed that BMI significantly mediated 16.78% of the association between eGDR and new-onset stroke. Subgroup analyses showed consistent associations across age, sex, and BMI categories.

Conclusion: This study highlights the significant and interconnected roles of BMI and eGDR in new-onset stroke risk, with a compounding effect observed in individuals with obesity and low eGDR. Addressing both insulin resistance and adiposity through targeted interventions could effectively reduce stroke risk, particularly in high-risk populations.

1 Introduction

New-onset stroke remains a critical global health issue, contributing significantly to morbidity and mortality, particularly among older adults. Stroke is a leading cause of disability-adjusted life years and the second most common cause of death worldwide (1). The Global Burden of Disease study estimates that over 12 million people suffered a first-time stroke in 2019, with low- and middle-income countries disproportionately affected (2). In China, the stroke burden is particularly severe, with stroke being the leading cause of death and disability (3). This underscores the urgent need to identify modifiable risk factors and implement targeted interventions to reduce stroke incidence and its associated health and economic burden.

Body mass index (BMI), a well-established metric of obesity, is a well-recognized risk factor for stroke (4, 5). Obesity exacerbates the risk of stroke through mechanisms such as increased blood pressure, dyslipidemia, and pro-inflammatory states, all of which impair vascular health (6, 7). While higher BMI is generally considered a risk factor for stroke, recent studies suggest a more complex, nonlinear relationship (8).

Estimated glucose disposal rate (eGDR), an indicator of insulin sensitivity, has emerged as a novel biomarker associated with metabolic health and cardiovascular risk. Insulin resistance (IR), defined as the need for higher doses of insulin to achieve a normal physiological response, has been linked to an increased risk of stroke through mechanisms such as atherosclerosis (9). Clinically, the euglycemic-hyperinsulinemic clamp is the gold standard for assessing IR, while the homeostasis model assessment of insulin resistance (HOMA-IR) serves as a widely accepted surrogate (10, 11). Due to the high cost and complexity of these methods, noninvasive alternatives, such as the estimated glucose disposal rate (eGDR), are gaining attention. Research has validated eGDR as an accurate measure of IR, with low eGDR levels significantly associated with increased mortality in individuals with diabetes (12). Additionally, eGDR has been identified as a predictor of adverse cardiovascular outcomes, including stroke (13). Whomever wrote this incompetently didn't know that stroke has been called neurological disease by the WHO since 2006!

However, research on the combined impact of eGDR and BMI on stroke remains limited and lacks systematic exploration. Moreover, the potential mediating role of BMI in the relationship between eGDR and stroke has not been thoroughly investigated. This study utilizes data from the China Health and Retirement Longitudinal Study (CHARLS) to investigate the associations of eGDR, BMI, and their combined effects on stroke risk, with the goal of providing insights that could inform prevention strategies tailored to high-risk populations in China.

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