Diabetes
Association of Hyperinsulinemia and Insulin Resistance with All-cause, Cardiovascular, and Cancer Mortality Among Non-diabetic Americans: The US National Health and Nutrition Examination Survey 1999-2018 Yixun Ke* Yixun Ke Roch A. Nianogo Chuyue Wu
ABSTRACT
Background: The effect of hyperinsulinemia and insulin resistance (HOMA-IR) on mortality outcomes, including all-cause mortality, cancer mortality, and cardiovascular disease (CVD) mortality, remains a topic of interest among non-diabetic Americans with and without obesity. This study examines the impact of hyperinsulinemia and insulin resistance (HOMA-IR) on mortality risks, including all-cause mortality, cardiovascular mortality and cancer mortality in the American population, utilizing NHANES data from 1999-2018.
Methods: This study includes 16,567 individuals from NHANES from 1999 to 2018, involving non-diabetic Americans with and without obesity. Mortality outcomes were ascertained by linkage to the National Center for Health Statistic Survey Data (NCHS). We employed the parametric g-formula to estimate the cumulative incidence of death for participants followed for at least 5 years and 10 years with and without hyperinsulinemia, and each HOMA-IR category. Pooled logistic regression models were used to calculate the HR and 95% confidence intervals (CIs) for all-cause mortality, cancer-cause mortality, and cardiovascular disease (CVD) cause mortality in individuals. We also performed stratified analyses based on age, gender and obesity subgroups.
Results: During a mean follow-up 143 months, a total of 2,316 deaths were documented, of which 711 were due to cardiovascular disease and 574 were due to cancer. Study outcomes reveal a significant relationship between hyperinsulinemia and increased cancer mortality (HR 1.92, 95% CI:1.27-2.88), notably more marked in nonobese subjects (HR 2.03, 95% CI: 1.24- 3.30), without corresponding elevations found in all-cause mortality or cardiovascular disease (CVD) cause mortality. The elevated risks noted in nonobese participants were not mirrored in the obese group across all mortality types.
Conclusion: The insights derived from NHANES data (1999-2018) enhance the understanding of hyperinsulinemia’s and insulin resistance’s role in mortality risks. These patterns highlight the critical role of metabolic health among nondiabetic individuals in mortality risk, emphasizing the importance of personalized interventions on hyperinsulinemia and insulin resistance regardless the presence or absence of obesity.
