The insulin sensitivity Mcauley index (MCAi) is associated with 40-year cancer mortality in a cohort of men and women free of diabetes at baseline

Abstract

Background: The association between insulin resistance and cancer-mortality is not fully explored. We investigated the association between several insulin sensitivity indices (ISIs) and cancer-mortality over 3.5 decades in a cohort of adult men and women. We hypothesized that higher insulin resistance will be associated with greater cancer-mortality risk.

Methods: A cohort of 1,612 men and women free of diabetes during baseline were followed since 1979 through 2016 according to level of insulin resistance (IR) for cause specific mortality, as part of the Israel study on Glucose Intolerance, Obesity and Hypertension (GOH). IR was defined according to the Mcauley index (MCAi), calculated by fasting insulin and triglycerides, the Homeostatic Model Assessment (HOMA), the Matsuda Insulin Sensitivity Index (MISI), and the Quantitative Insulin Sensitivity Check Index (QUICKI), calculated by plasma glucose and insulin.

Results: Mean age at baseline was 51.5 ± 8.0 years, 804 (49.9%) were males and 871 (54.0%) had prediabetes. Mean follow-up was 36.7±0.2 years and 47,191 person years were accrued. Cox proportional hazard model and competing risks analysis adjusted for age, sex, country of origin, BMI, blood pressure, total cholesterol, smoking and glycemic status, revealed an increased risk for cancer-mortality, HR = 1.5 (95% CI: 1.1-2.0, p = 0.005) for the MCAi Q1 compared with Q2-4. No statistically significant associations were observed between the other ISIs and cancer-mortality.

Conclusion: The MCAi was independently associated with an increased risk for cancer-mortality in adult men and women free of diabetes and should be further studied as an early biomarker for cancer risk.

Fig 1. Adjusted^a survival curves using the Cox proportional hazard model, according to the Mcauley index low vs. higher quartiles for cancer mortality.

^a Adjusted for: age, sex, origin, BMI, systolic blood pressure, cholesterol, smoking and diabetes status. Mean survival time for malignancy associated mortality in the lower (higher insulin resistance) MCA quartile (Q₁) was 35.8 (95%CI, 34.9–36.7) years and 36.9 (95%CI, 36.5–37.4) years in the upper (lower insulin resistance) MCA quartiles (Q_2-4), p = 0.02. Censoring occurred at time of other non-cancer death or end of follow-up.