Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community

Abstract

Background Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease. Methods We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR < 1.5), presence of insulin resistance (HOMA-IR ≥ 1.5) and diabetes mellitus (DM). Multivariable logistic regression models were conducted to evaluate the association between abnormal glucose metabolism and impaired LVGLS (> − 16.65%). Results Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e′ ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (− 17.6 ± 2.6% vs. − 19.7 ± 3.1%, p < 0.05). The prevalence of impaired LVGLS was higher in abnormal HOMA-IR group compared with normal HOMA-IR group (42.4% vs. 14.0%) and similar to that of DM (48.9%). In multivariable analyses, glycemic abnormalities were significantly associated with impaired LVGLS, independent of traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters [adjusted odds ratio (OR) 2.38, p = 0.007 for abnormal HOMA-IR; adjusted OR 3.02, p = 0.003 for DM]. The independent association persisted even after adjustment for waist circumference as a marker of abdominal adiposity. Sub-group analyses stratified by body mass index showed significant association between abnormal HOMA-IR and impaired LVGLS in normal weight individuals (adjusted OR 4.59, p = 0.001), but not in overweight/obese individuals (adjusted OR 1.62, p = 0.300). Conclusions In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.

Glucose dysregulation and subclinical cardiac dysfunction in older adults: The Cardiovascular Health Study

“…Both the Coronary Artery Risk Development in Young Adult (CARDIA) and Framingham Heart Study (FHS) Offspring and 3rd generation cohorts, 3179 and 6231 participants respectively, found that higher HOMA-IR was associated with worse LVLS, a finding that persisted after adjustment for waist circumference [ 14 , 15 ]. Similar results were observed in a smaller study of 539 Japanese participants [ 26 ]. Additionally, the CARDIA study also found that higher HOMA-IR was also associated with worse LVDSR [ 14 ].…”

“…The association between fasting glucose measures and adverse cardiac mechanics has been previously evaluated in population-based cohorts free of baseline cardiovascular disease but these comprised younger individuals and mainly focused on LVLS measures [ 14 – 16 , 26 ]. The mean participant age for these studies was between 50 and 60 years old.…”

Endocrine system dysfunction and chronic heart failure: a clinical perspective

“…Diabetes mellitus decreases remarkably the survival probability in patients diagnosed with CHF, and the risk is strictly affected by diabetes evolution and the level of glucose control over time. Insulin resistance carriers increased risk of heart failure as observed in early stage in patients without evidence of overt cardiac disease [196]. Similar findings have also been found in individuals with apparently uncomplicated type 2 diabetes mellitus whose exercise tolerance was reduced [197].…”

Insulin Therapy is Associated With Increased Myocardial Interstitial Fibrosis and Cardiomyocyte Apoptosis in a Rodent Model of Experimental Diabetes

“…Insulin is used in approximately one-third of patients with diabetes ( Trief et al, 2016 ), and it has emerged as an independent risk factor for left ventricular dysfunction ( Hirose et al, 2021 ) and heart failure hospitalizations ( Nichols et al, 2004 ; Wang et al, 2015 ). In addition to insulin causing sodium retention and being indicative of a more advanced diabetic state ( Cosmi et al, 2018 ), our findings suggest that it can inflict direct adverse changes to the left ventricular tissue.…”

“…Insulin use, which is common in up to one-third of DM patients ( Trief et al, 2016 ), is an independent risk factor for the development of heart failure ( Nichols et al, 2004 ; Wang et al, 2015 ) and LV dysfunction ( Hirose et al, 2021 ). Moreover, among patients with systolic heart failure, insulin therapy was associated with a higher 1-year mortality rate ( Smooke et al, 2005 ).…”