Abstract 4944: Insulin resistance and long-term cancer-specific and all-cause mortality: The Women's Health Initiative (WHI)
Authors: Pan Kathy , Nelson Rebecca , Wactawski-Wende Jean , Lee Delphine J. , Manson JoAnn E. , Mortimer Joanne E. , Phillips Lawrence S. , Rohan Thomas , Ho Gloria Y. , Saquib Nazmus , Shadyab Aladdin H. , Nassir Rami , Rhee Jinnie J. , Hurria Arti , Chlebowski Rowan T. 
Published: August 2018

Abstract
Background: Elevated insulin resistance has been associated with multiple morbid conditions. To our review, only one cohort study has evaluated insulin resistance and all-cause mortality in a general population (Pyorala 2000).
Objective: To examine associations of insulin resistance with long-term cancer-specific and all-cause mortality in postmenopausal women.
Methods: Included were 22,837 postmenopausal women aged 50-79 from the WHI cohort without prior cancer and with available fasting glucose and insulin levels. Using multivariate Cox proportional hazard models, we compared cancer-specific and all-cause mortality across quartiles of insulin resistance estimated by the homeostasis model assessment-insulin resistance (HOMA-IR) index.
Results: Women in the highest HOMA-IR quartile were less educated, had higher BMI and waist circumference, were more likely to be Black, and were more likely to have hypertension than those in lower HOMA-IR quartiles. Women in the highest quartile were also significantly more likely to have a history of treated diabetes than those in lower quartiles (23.5% in Q4 versus 0.6% in Q1). After a median follow-up of 18.1 years, cancer-specific and all-cause mortality were significantly higher in the highest HOMA-IR quartile compared to the lowest (HR 1.25, 95% CI 1.07-1.46 and HR 1.62, 95% CI 1.50-1.75, respectively) (Table 1). In a sensitivity analysis excluding women with treated diabetes (remaining n=21,104), all-cause mortality findings were similar (HR 1.36, 95% CI 1.25-1.48, p&lt;0.0001). Specific causes of the 7,194 total deaths were cancer (1,786, 25%), cardiovascular disease (2,458, 34%), Alzheimer's/dementia (549, 8%), other (2,041, 28%), and unknown (360, 5%).
Conclusion: Insulin resistance by HOMA-IR index identifies a substantial, previously under-recognized population of postmenopausal women at increased risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.
Table 1. Adjusted* HRs for cancer-specific and all-cause mortality by HOMA-IR quartilesHOMA-IR QuartilesNCancer Specific Mortality HR (95% CI) P valueAll Cause Mortality HR (95% CI) P valueQ1: 0.04-1.0857071.0 (reference)0.04311.0 (reference)&lt;0.0001Q2: 1.09-1.7657131.11 (0.97-1.28)1.13 (1.05-1.21)Q3: 1.77-3.0257161.17 (1.01-1.36)1.20 (1.11-1.29)Q4: 3.03-40357011.25 (1.07-1.46)1.62 (1.50-1.75)*Adjusted for education level, BMI, age at menopause, parity, alcohol consumption, and Gail score
Citation Format: Kathy Pan, Rebecca Nelson, Jean Wactawski-Wende, Delphine J. Lee, JoAnn E. Manson, Joanne E. Mortimer, Lawrence S. Phillips, Thomas Rohan, Gloria Y. Ho, Nazmus Saquib, Aladdin H. Shadyab, Rami Nassir, Jinnie J. Rhee, Arti Hurria, Rowan T. Chlebowski. Insulin resistance and long-term cancer-specific and all-cause mortality: The Women's Health Initiative (WHI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4944.