Background/Aims: We aimed to unravel how symptoms related to gastrointestinal (GI) dysfunction impair quality of life (QoL) in patients with diabetes mellitus (DM). Methods: We enrolled 134 outpatients with type 2 DM and 16 non-DM. In DM patients, mean age was 64.7 years, mean body mass index (BMI) 24.7 kg/m2, mean glycated hemoglobin (HbA1c) 7.1%, and mean DM duration 13.7 years. In non-DM, mean age was 66.6 years and mean BMI was 25.2 kg/m2. GI symptom-related QoL was determined using the Izumo scale, based on five factors, i.e., heartburn, gastralgia, postprandial fullness, constipation and diarrhea. The sum of scores obtained for the three questions in each domain was calculated, and subjects with a score of 5 or higher were considered to be symptomatic with impaired QoL. JMP Clinical version 5.0 was used for all statistical analyses. Results: In DM patients, constipation was much greater than non-DM, diarrhea was somewhat higher, other symptoms did not increase significantly. In DM, lower abdominal symptoms were found to be more frequent than those affecting the upper abdomen. Diabetic duration and medications showed associations with GI symptoms. We identified differences in peak prevalences of the five symptoms. Gastralgia and total GI symptoms peaked at a diabetes duration of 15-19 years. Heartburn and postprandial fullness tended to increase with disease duration. Constipation and diarrhea showed bimodal peaks, with the first early and the second late in the disease course. Finally, GI symptoms showed clustering that reflected the region of the GI tract affected, i.e., constipation and diarrhea had similar frequencies. Conclusions: Our study highlights the importance of questioning patients about QoL impairment due to abdominal symptoms, especially in the early and the late periods of diabetes. The heterogeneous nature of the underlying GI symptoms, including medication usage, should be taken into consideration when managing patients with T2DM. Disclosure M. Fujishiro: Research Support; Self; Johnson & Johnson Services, Inc. A. Kushiyama: Research Support; Self; Teijin Pharma Limited, Sanwa Kagaku Kenkyusho Co., Ltd., Kowa Pharmaceutical Co., Ltd, StaGen. Consultant; Self; RIZAP. H. Yamazaki: None. T. Yamamotoya: None. T. Kikuchi: None. H. Sakoda: None. R. Suzuki: Research Support; Self; Daiichi Sankyo Company, Limited, Kyowa Hakko Kirin Co., Ltd.. Other Relationship; Self; MSD K.K., Novo Nordisk Pharma Ltd., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.