Insulin Resistance, Subclinical Left Ventricular Remodeling, and the Obesity Paradox

Abstract

Objectives We assessed in the Multi-Ethnic Study of Atherosclerosis (MESA) whether impaired fasting glucose, insulin resistance, and waist-to-hip ratio had effects on cardiac remodeling, independent of obesity. Background Recent studies suggest that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI). Methods We investigated 4,364 individuals without diabetes in MESA. Impaired fasting glucose (IFG: 100-125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance, HOMA-IR) and waist-to-hip ratio (WHR) were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on LV remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging. Results Individuals with IFG were more likely to be older, hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, individuals with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p<0.05 for all). HOMA-IR (p<0.0001), WHR (p<0.0001), and the presence of IFG (p=0.04), but not BMI (p=0.24), were independently associated with LV mass-to-volume ratio after adjustment for age, gender, hypertension, race, and dyslipidemia. Conclusions Insulin resistance and waist-to-hip ratio are associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI.

Visceral adiposity and left ventricular remodeling: The Multi-Ethnic Study of Atherosclerosis

“…However, whether the degree of obesity itself—or its associated inflammation and insulin resistance—produces myocardial changes remains unclear. Indeed, using data from the Multi-Ethnic Study of Atherosclerosis (MESA), our group has reported a BMI-independent association between impaired fasting glucose and cardiac remodeling by cardiac magnetic resonance (CMR) imaging 4 , consistent with other large, community based cohorts 5 . These results suggest that cardiometabolic changes may be mediators of obesity-related cardiac remodeling and incident HF.…”

Relation of Insulin Resistance to Longitudinal Changes in Left Ventricular Structure and Function in a General Population

“…For instance, 2 cross‐sectional, community‐based studies demonstrated an independent association between the degree of insulin resistance (by HOMA‐IR) and increased LVMI and LV mass to volume ratio assessed by MRI 10, 11. In addition, insulin resistance was also associated with LV diastolic dysfunction, namely with increased E/e′ and decreased TDI e′ velocity 12, 13.…”

“…Previous cross‐sectional large‐scale community‐based studies have demonstrated an independent association of subclinical LV remodeling and dysfunction with insulin resistance 10, 11, 12, 13, 14, 15. On the other hand, population data on the longitudinal changes of LV structure and function in relation to insulin resistance are sparse.…”

Visceral Adiposity and the Risk of Metabolic Syndrome Across Body Mass Index

“…Fasting blood samples collected at examination 3 were used to quantify selected adipokines reflecting insulin resistance and systemic inflammation (interleukin-6, high-sensitivity C-reactive protein [CRP], leptin, adiponectin, insulin, and tumor necrosis factor-α) as previously described (10,11). Protocols were approved by the Institutional Review Board at each participating institution.…”