The association between insulin sensitivity indices, ECG findings and mortality: a 40 year cohort study

Introduction: Type 2 Diabetes is a major risk factor for cardiovascular (CV) mortality. Insulin resistance can be evaluated non-invasively by insulin sensitivity indices (ISI) such as the Mcauley index (MCAi). Currently, the association between ISIs and ECG findings and all-cause and CV mortality is still not established in a large scale and heterogeneous population.

Material and method: 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 CV-mortality and December-2019 for all-cause mortality. ECGs were recorded and OGTTs performed during baseline. ISIs were categorized into quartiles and evaluated against ECG findings and all-cause and CV-mortality.

Results and discussion: 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 Mcauley-index (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 CV-mortality (HR=1.4, 95%CI 1.1-1.8) compared with Q2-4-MCAi. Individuals in Q4-Ln Homeostatic model assessment- Insulin Resistance (HOMA-IR) and Q1- Quantitative Insulin Sensitivity Check Index (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 CV-mortality.

Conclusion: Higher insulin-resistance, according to the MCAi, associated with ECG-changes, and with greater risk for all-cause and CV-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.