Excessively Low Insulin Resistance May Increase the Risk of All-Cause Mortality Among Community-Dwelling Individuals Without Diabetes

Background Epidemiological evidence has indicated that insulin resistance (IR), as measured by a homeostatic model assessment for IR (HOMA-IR), is strongly correlated with body mass index (BMI). However, there is a paucity of studies assessing the complex interaction between BMI and HOMA-IR with respect to all-cause mortality, particularly among Asian individuals without diabetes. Materials and methods The research centered on individuals diagnosed without diabetes, comprising 881 men with a mean age of 62 years (± standard deviation (SD): 14) and 1,159 women with a mean age of 64 years (± 11). The participants were drawn from the Nomura cohort study, consisting of two cohorts: one initiated in 2002 and the other in 2014. To assess the risk of all-cause mortality up to the end of the follow-up period, we applied a Cox proportional hazards model, adjusting for a range of covariates to calculate the hazard ratios (HRs). Results Participants were followed for a median duration of 7,691 days (interquartile range: 4,235-7,761 days). Over the course of the follow-up period, a total of 672 deaths were documented, comprising 338 deaths among men and 334 among women. The interaction between BMI and HOMA-IR (HR: 1.05; 95% confidence interval (CI): 1.02-1.09) was significantly associated with all-cause mortality, along with gender, age, BMI, history of cardiovascular disease, hyperuricemia, and HOMA-IR. Moreover, the HRs for all-cause mortality were examined for each BMI group by dividing the HOMA-IR by one SD. In the BMI < 22.0 kg/m² group, using the third HOMA-IR as the reference, significant HR (J curve) increases were observed in the first, second, and fourth HOMA-IR. In the BMI ≥ 22.0 kg/m² group, using the first HOMA-IR as the reference, a significant increase in HR was observed only in the fourth HOMA-IR. An interaction between BMI and HOMA-IR was identified for all-cause mortality (p = 0.005). Conclusions BMI confounds the association between IR, as measured by HOMA-IR, and the risk of all-cause mortality among Japanese individuals.