e22073 Background: Diabetes mellitus (DM) is one of the common morbidities in United States. Insulin therapy has been frequently used in its treatment. Some studies have postulated that activation of Insulin and Insulin-like growth factor (IGF) pathway may contribute to cancer proliferation, growth and resistance to anticancer therapies. The impact of insulin on diabetic patients with non-small cell lung cancer (NSCLC) has not been reported. Methods: 1,233 patients with NSCLC diagnosed between January 1999 and December 2004 were identified from the Tumor Registry at Henry Ford Health System. Based on inclusion criteria, data from 1,206 patients were extracted from the electronic medical records. Statistical analyses were performed between insulin and non insulin users. Results: Out of 1,206 patients, 193 patients had NSCLC and DM. Data was available from 192 patients. Sixty (31.3%) were on insulin at the time of NSCLC diagnosis and defined as insulin users, while 132 were not on insulin and defined as non- users (68.7%). Demographics, co-morbidities, disease stage at diagnosis, therapeutic interventions, and laboratory values were analyzed for overall and cancer-specific survival. More insulin users (81%) than non-users (64%) presented with advanced disease (stage ≥ 3) at diagnosis (P=0.02). Although no significant difference of Hemoglobin A1c was observed, the median survival from all causes of death was 6.5 months for insulin-users versus 9.9 months for non-users (P=0.08). When survival time was calculated from cancer-specific death, the median survival between insulin and non-insulin users was 7.2 months versus 38.7 months, respectively (P=0.002), with a hazard ratio (HR) for insulin use equals 1.91. Results from our univariable and multivariable analyses will be presented at the ASCO annual meeting in detail. Conclusions: This data indicates that the use of insulin may adversely affect the biology and clinical course of NSCLC with a tendency of advanced disease stage at diagnosis and a shorter cancer-specific survival time. Prospective study of DM with NSCLC or other cancer diagnosis will improve our understanding of this potential adverse effect on cancer biology and provide scientific rational to target IGF-pathway especially in diabetic patients. No significant financial relationships to disclose.