The Association Between Insulin Sensitivity Indices, ECG Findings and Mortality: A 40 Year Cohort Study

Abstract Background: Type 2 Diabetes is associated with insulin resistance and is a major risk factor for cardiovascular mortality. Insulin resistance can be evaluated non-invasively by insulin sensitivity indices, like the Mcauley index (MCAi), which is a function of fasting plasma insulin and triglycerides. We sought to further elucidate the association between insulin sensitivity indices and incidental ECG findings and all-cause and cardiovascular mortality in a large cohort followed for decades. Methods: In a prospective study of the Israel cohort on Glucose Intolerance, Obesity and Hypertension (GOH) second phase (1979-1982) 1830 men and women were followed until December 2016 for cardiovascular mortality and December 2019 for all-cause mortality. ECGs were recorded and oral glucose tolerance tests performed during baseline. Insulin sensitivity indices were categorized into quartiles and evaluated against ECG findings and all-cause and cardiovascular mortality.Results: Mean age at baseline was 52.0±8.1 years, and 75 (15.2%) and 47 (25.3%) participants in the upper quartiles (Q2-4) and the lower quartile (Q1) of the MCAi, presented with ischemic changes on ECG respectively (p=0.02). Multivariable analysis showed higher odds for ECG ischemic changes, for individuals in Q1-MCAi (adjusted OR=1.7, 95%CI 1.02-2.8), compared with Q2-4-MCAi, which attenuated when excluding individuals with diabetes (adjusted OR=1.6, 95%CI 0.9-2.7, p=0.09). Cox proportional-hazards regression showed an increased risk for all-cause mortality for individuals in Q1-MCAi (HR=1.2, 95%CI 1.02-1.3) as well as an increased risk for cardiovascular mortality (HR=1.4, 95%CI 1.1-1.8) compared with Q2-4-MCAi. Individuals in Q4-Ln HOMA-IR and Q1-QUICKI also presented with increased risk for all-cause-mortality (HR=1.2, 95%CI 1.04-1.4; and HR=1.2, 95%CI 1.04-1.4, respectively). Other ISIs did not show significant association with cardiovascular mortality. Conclusions: Higher insulin-resistance, according to the MCAi, associated with ECG changes, and with greater risk for all-cause and cardiovascular mortality over a 40-year follow-up. The MCAi may be considered as an early predictive and prognostic biomarker for CV-morbidity and mortality in adults.